## Protocol Section
### Identification Module
**NCT ID:** NCT03759379

**Brief Title:** HELIOS-A: A Study of Vutrisiran (ALN-TTRSC02) in Patients With Hereditary Transthyretin Amyloidosis (hATTR Amyloidosis)

**Official Title:** HELIOS-A: A Phase 3 Global, Randomized, Open-label Study to Evaluate the Efficacy and Safety of ALN-TTRSC02 in Patients With Hereditary Transthyretin Amyloidosis (hATTR Amyloidosis)

#### Organization Study ID Info
**ID:** ALN-TTRSC02-002
#### Organization
**Class:** INDUSTRY
**Full Name:** Alnylam Pharmaceuticals
#### Secondary ID Infos
**ID:** 2018-002098-23
**Type:** EUDRACT_NUMBER
### Status Module
#### Completion Date
**Date:** 2026-10

**Type:** ESTIMATED

#### Disp First Post Date
**Date:** 2021-11-15

**Type:** ACTUAL

**Disp First Submit Date:** 2021-11-09
**Disp First Submit QC Date:** 2021-11-09

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-03-20

**Type:** ACTUAL

**Last Update Submit Date:** 2024-03-18

**Overall Status:** ACTIVE_NOT_RECRUITING

#### Primary Completion Date
**Date:** 2020-11-10

**Type:** ACTUAL

#### Results First Post Date
**Date:** 2022-08-11

**Type:** ACTUAL

**Results First Submit Date:** 2022-07-12

**Results First Submit QC Date:** 2022-07-12

#### Start Date
**Date:** 2019-02-14

**Type:** ACTUAL

**Status Verified Date:** 2023-03

#### Study First Post Date
**Date:** 2018-11-30
**Type:** ACTUAL
**Study First Submit Date:** 2018-11-28
**Study First Submit QC Date:** 2018-11-28
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Alnylam Pharmaceuticals

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** The purpose of this study is to evaluate the efficacy and safety of vutrisiran (ALN-TTRSC02) in participants with hereditary transthyretin amyloidosis (hATTR amyloidosis). Participants will receive vutrisiran subcutaneous (SC) injection once every 3 months (q3M) or the reference comparator patisiran intravenous (IV) injection once every 3 weeks (q3w) during the 18 month Treatment Period. This study will use the placebo arm of the APOLLO study (NCT01960348) as an external comparator for the primary and most other efficacy endpoints during the 18 Month Treatment Period. Following the 18 Month Treatment Period, all participants will be randomized to receive vutrisiran SC injection once every 6 months (q6M) or q3M in the Randomized Treatment Extension (RTE) Period.

### Conditions Module

**Conditions:**

- Amyloidosis, Hereditary

- Transthyretin Amyloidosis

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 164

**Type:** ACTUAL

**Phases:**

- PHASE3

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Participants will receive vutrisiran 25 mg subcutaneous (SC) injection once every 3 months (q3M) for 18 months during the Treatment Period followed by vutrisiran SC injection once every 6 months (q6M) or q3M during the Randomized Treatment Extension (RTE) Period.

**Intervention Names:**

- Drug: Vutrisiran

**Label:** Vutrisiran + Vutrisiran (HELIOS-A)

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Participants will receive patisiran 0.3 mg/kg intravenous (IV) infusion once every 3 weeks (q3w) for 18 months during the Treatment Period followed by vutrisiran SC injection q6M or q3M during the RTE Period.

**Intervention Names:**

- Drug: Patisiran

- Drug: Vutrisiran

**Label:** Patisiran + Vutrisiran (HELIOS-A)

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Patisiran + Vutrisiran (HELIOS-A)

**Description:** Patisiran will be administered by IV infusion.

**Name:** Patisiran

**Other Names:**

- ONPATTRO

- ALN-TTR02

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Patisiran + Vutrisiran (HELIOS-A)

- Vutrisiran + Vutrisiran (HELIOS-A)

**Description:** Vutrisiran will be administered by SC injection.

**Name:** Vutrisiran

**Other Names:**

- ALN-TTRSC02

- AMVUTTRA

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** The mNIS+7 is a composite score that measures neurologic impairment which includes the following components: physical exam of lower limbs, upper limbs and cranial nerves to assess motor strength/weakness, electrophysiologic measurement of small and large nerve fiber function, sensory testing and postural blood pressure. The mNIS+7 is scored from 0 (no impairment) to 304 points (maximum impairment). A higher score indicates a worse outcome.

**Measure:** Change From Baseline in the Modified Neurologic Impairment Score +7 (mNIS+7) at Month 9 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)]

**Time Frame:** Baseline, Month 9

#### Secondary Outcomes

**Description:** The Norfolk QoL-DN questionnaire is a standardized 35-item patient-reported outcomes measure that is sensitive to the different features of diabetic neuropathy - small fiber, large fiber, and autonomic nerve function. The total score ranges from -4 (best possible quality of life) to 136 points (worst possible quality of life). A higher score indicates a worse outcome.

**Measure:** Change From Baseline in Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) Total Score at Month 9 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)]

**Time Frame:** Baseline, Month 9

**Description:** The 10-MWT is a measure of ambulatory ability and measures the time (in seconds) that it takes a participant to walk 10 meters (gait speed). An increase in gait speed from baseline represents improvement, and a decrease from baseline represents worsening.

**Measure:** Change From Baseline in the Timed 10-Meter Walk Test (10-MWT) at Month 9 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)]

**Time Frame:** Baseline, Month 9

**Description:** The mNIS+7 is a composite score that quantifies motor, sensory, and autonomic neurologic impairment due to injury of large and small nerves. The mNIS+7 is scored from 0 (no impairment) to 304 points (maximum impairment). A higher score indicates a worse outcome.

**Measure:** Change From Baseline in the Modified Neurologic Impairment Score +7 (mNIS+7) at Month 18 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)]

**Time Frame:** Baseline, Month 18

**Description:** The Norfolk QoL-DN questionnaire is a standardized 35-item patient-reported outcomes measure that is sensitive to the different features of diabetic neuropathy - small fiber, large fiber, and autonomic nerve function. The total score ranges from -4 (best possible quality of life) to 136 points (worst possible quality of life). A higher score indicates a worse outcome.

**Measure:** Change From Baseline in Norfolk QoL-DN Total Score at Month 18 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)]

**Time Frame:** Baseline, Month 18

**Description:** The 10-MWT is a measure of ambulatory ability and measures the time (in seconds) that it takes a participant to walk 10 meters (gait speed). An increase in gait speed from baseline represents improvement, and a decrease from baseline represents worsening.

**Measure:** Change From Baseline in the 10-MWT at Month 18 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)]

**Time Frame:** Baseline, Month 18

**Description:** The mBMI, which is a measure of nutritional status, is calculated as the product of body mass index (BMI) (weight in kilograms divided by the square of height in meters) and serum albumin (g/L) to reflect fluid balance, such as fluid accumulation or dehydration. A negative change from baseline indicates a better outcome.

**Measure:** Change From Baseline in the Modified Body Mass Index (mBMI) at Month 18 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)]

**Time Frame:** Baseline, Month 18

**Description:** The R-ODS is a patient-reported measure of level of disability on a scale of 0-48, with 0 being the worst and 48 the best (no limitations); scores are based on activities of daily living and social participation. An increase in R-ODS from baseline suggests improvement in disability, and a decrease from baseline suggests worsening of disability.

**Measure:** Change From Baseline in the Rasch-Built Overall Disability Scale (R-ODS) at Month 18 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)]

**Time Frame:** Baseline, Month 18

**Description:** Serum TTR was assessed at multiple timepoints up to Month 18.

**Measure:** Percent Reduction in Serum Transthyretin (TTR) Levels Through Month 18 Between the Vutrisiran Group (HELIOS-A) and the Patisiran Group (HELIOS-A)

**Time Frame:** Up to Month 18

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Male or female of 18 to 85 years of age (inclusive);
* Has a diagnosis of hATTR amyloidosis with transthyretin (TTR) mutation;
* Has adequate neurologic impairment score (NIS);
* Has adequate polyneuropathy disability (PND) score;
* Has adequate Karnofsky Performance Status (KPS).

Exclusion Criteria:

* Had a prior liver transplant or is likely to undergo liver transplantation during the study;
* Has known other (non-hATTR) forms of amyloidosis or leptomeningeal amyloidosis;
* Has New York Heart Association heart failure classification \>2;
* Clinically significant liver function test abnormalities;
* Has known human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis B virus (HBV) infection;
* Received an experimental drug within 30 days of dosing;
* Received prior TTR-lowering treatment;
* Has other known causes of neuropathy.

**Maximum Age:** 85 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** San Diego

**Country:** United States

**Facility:** Clinical Trial Site

**State:** California

**Zip:** 92120

**Location 2:**

**City:** Aurora

**Country:** United States

**Facility:** Clinical Trial Site

**State:** Colorado

**Zip:** 80045

**Location 3:**

**City:** Chicago

**Country:** United States

**Facility:** Clinical Trial Site

**State:** Illinois

**Zip:** 97239

**Location 4:**

**City:** Baltimore

**Country:** United States

**Facility:** Clinical Trial Site

**State:** Maryland

**Zip:** 21205

**Location 5:**

**City:** Boston

**Country:** United States

**Facility:** Clinical Trial Site

**State:** Massachusetts

**Zip:** 02118

**Location 6:**

**City:** Rochester

**Country:** United States

**Facility:** Clinical Trial Site

**State:** Minnesota

**Zip:** 55905

**Location 7:**

**City:** Saint Louis

**Country:** United States

**Facility:** Clinical Trial Site

**State:** Missouri

**Zip:** 63130

**Location 8:**

**City:** New York

**Country:** United States

**Facility:** Clinical Trial Site

**State:** New York

**Zip:** 10032

**Location 9:**

**City:** Chapel Hill

**Country:** United States

**Facility:** Clinical Trial Site

**State:** North Carolina

**Zip:** 27599

**Location 10:**

**City:** Columbus

**Country:** United States

**Facility:** Clinical Trial Site

**State:** Ohio

**Zip:** 43210

**Location 11:**

**City:** Portland

**Country:** United States

**Facility:** Clinical Trial Site

**State:** Oregon

**Zip:** 97239

**Location 12:**

**City:** Philadelphia

**Country:** United States

**Facility:** Clinical Trial Site

**State:** Pennsylvania

**Zip:** 19140

**Location 13:**

**City:** Fort Worth

**Country:** United States

**Facility:** Clinical Trial Site

**State:** Texas

**Zip:** 75246

**Location 14:**

**City:** Buenos Aires

**Country:** Argentina

**Facility:** Clinical Trial Site

**Location 15:**

**City:** Box Hill

**Country:** Australia

**Facility:** Clinical Trial Site

**Location 16:**

**City:** Westmead

**Country:** Australia

**Facility:** Clinical Trial Site

**Location 17:**

**City:** Woolloongabba

**Country:** Australia

**Facility:** Clinical Trial Site

**Location 18:**

**City:** Bruxelles

**Country:** Belgium

**Facility:** Clinical Trial Site

**Location 19:**

**City:** Leuven

**Country:** Belgium

**Facility:** Clinical Trial Site

**Location 20:**

**City:** Rio De Janeiro

**Country:** Brazil

**Facility:** Clinical Trial Site

**Location 21:**

**City:** Sofia

**Country:** Bulgaria

**Facility:** Clinical Trial Site

**Location 22:**

**City:** Montréal

**Country:** Canada

**Facility:** Clinical Trial Site

**Location 23:**

**City:** Vancouver

**Country:** Canada

**Facility:** Clinical Trial Site

**Location 24:**

**City:** Nicosia

**Country:** Cyprus

**Facility:** Clinical Trial Site

**Location 25:**

**City:** Bordeaux

**Country:** France

**Facility:** Clinical Trial Site

**Location 26:**

**City:** Créteil

**Country:** France

**Facility:** Clinical Trial Site

**Location 27:**

**City:** Marseille

**Country:** France

**Facility:** Clinical Trial Site

**Location 28:**

**City:** Paris

**Country:** France

**Facility:** Clinical Trial Site

**Location 29:**

**City:** Mainz

**Country:** Germany

**Facility:** Clinical Trial Site

**Location 30:**

**City:** Münster

**Country:** Germany

**Facility:** Clinical Trial Site

**Location 31:**

**City:** Athens

**Country:** Greece

**Facility:** Clinical Trial Site

**Location 32:**

**City:** Messina

**Country:** Italy

**Facility:** Clinical Trial Site

**Location 33:**

**City:** Pavia

**Country:** Italy

**Facility:** Clinical Trial Site

**Location 34:**

**City:** Rome

**Country:** Italy

**Facility:** Clinical Trial Site

**Location 35:**

**City:** Kumamoto

**Country:** Japan

**Facility:** Clinical Trial Site

**Location 36:**

**City:** Nagano

**Country:** Japan

**Facility:** Clinical Trial Site

**Location 37:**

**City:** Nagoya

**Country:** Japan

**Facility:** Clinical Trial Site

**Location 38:**

**City:** Osaka

**Country:** Japan

**Facility:** Clinical Trial Site

**Location 39:**

**City:** Junggu

**Country:** Korea, Republic of

**Facility:** Clinical Trial Site

**Location 40:**

**City:** Kuala Lumpur

**Country:** Malaysia

**Facility:** Clinical Trial Site

**Location 41:**

**City:** Mexico City

**Country:** Mexico

**Facility:** Clinical Trial Site

**Location 42:**

**City:** Groningen

**Country:** Netherlands

**Facility:** Clinical Trial Site

**Location 43:**

**City:** Lisboa

**Country:** Portugal

**Facility:** Clinical Trial Site

**Location 44:**

**City:** Porto

**Country:** Portugal

**Facility:** Clinical Trial Site

**Location 45:**

**City:** Barcelona

**Country:** Spain

**Facility:** Clinical Trial Site

**Location 46:**

**City:** Huelva

**Country:** Spain

**Facility:** Clinical Trial Site

**Location 47:**

**City:** Madrid

**Country:** Spain

**Facility:** Clinical Trial Site

**Location 48:**

**City:** Valencia

**Country:** Spain

**Facility:** Clinical Trial Site

**Location 49:**

**City:** Solna

**Country:** Sweden

**Facility:** Clinical Trial Site

**Location 50:**

**City:** Umeå

**Country:** Sweden

**Facility:** Clinical Trial Site

**Location 51:**

**City:** Taipei City

**Country:** Taiwan

**Facility:** Clinical Trial Site

**Location 52:**

**City:** Taipei

**Country:** Taiwan

**Facility:** Clinical Trial Site

**Location 53:**

**City:** London

**Country:** United Kingdom

**Facility:** Clinical Trial Site

#### Overall Officials

**Official 1:**

**Affiliation:** Alnylam Pharmaceuticals

**Name:** Medical Director

**Role:** STUDY_DIRECTOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

### References Module

#### References

**Citation:** Adams D, Tournev IL, Taylor MS, Coelho T, Plante-Bordeneuve V, Berk JL, Gonzalez-Duarte A, Gillmore JD, Low SC, Sekijima Y, Obici L, Chen C, Badri P, Arum SM, Vest J, Polydefkis M; HELIOS-A Collaborators. Efficacy and safety of vutrisiran for patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy: a randomized clinical trial. Amyloid. 2023 Mar;30(1):1-9. doi: 10.1080/13506129.2022.2091985. Epub 2022 Jul 23.

**PMID:** 35875890

## Document Section

### Large Document Module

#### Large Docs

- Date: 2021-02-19

- Filename: Prot_000.pdf

- Has ICF: False

- Has Protocol: True

- Has SAP: False

- Label: Study Protocol

- Size: 9085902

- Type Abbrev: Prot

- Upload Date: 2022-07-12T11:46

- Date: 2021-08-24

- Filename: SAP_001.pdf

- Has ICF: False

- Has Protocol: False

- Has SAP: True

- Label: Statistical Analysis Plan

- Size: 8347637

- Type Abbrev: SAP

- Upload Date: 2022-07-12T11:51

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000057165

- Term: Proteostasis Deficiencies

- ID: D000008659

- Term: Metabolic Diseases

- ID: D000020271

- Term: Heredodegenerative Disorders, Nervous System

- ID: D000019636

- Term: Neurodegenerative Diseases

- ID: D000009422

- Term: Nervous System Diseases

- ID: D000017772

- Term: Amyloid Neuropathies

- ID: D000010523

- Term: Peripheral Nervous System Diseases

- ID: D000009468

- Term: Neuromuscular Diseases

- ID: D000030342

- Term: Genetic Diseases, Inborn

- ID: D000008661

- Term: Metabolism, Inborn Errors

### Condition Browse Module - Browse Branches

- Abbrev: BC18

- Name: Nutritional and Metabolic Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: BC16

- Name: Diseases and Abnormalities at or Before Birth

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M4021

- Name: Amyloidosis

- Relevance: HIGH

- As Found: Amyloidosis

- ID: M23330

- Name: Amyloid Neuropathies, Familial

- Relevance: HIGH

- As Found: Transthyretin Amyloidosis

- ID: M19981

- Name: Amyloid Neuropathies

- Relevance: LOW

- As Found: Unknown

- ID: M23329

- Name: Amyloidosis, Familial

- Relevance: HIGH

- As Found: Amyloidosis, Hereditary

- ID: M28747

- Name: Proteostasis Deficiencies

- Relevance: LOW

- As Found: Unknown

- ID: M11639

- Name: Metabolic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M22092

- Name: Heredodegenerative Disorders, Nervous System

- Relevance: LOW

- As Found: Unknown

- ID: M21558

- Name: Neurodegenerative Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M13432

- Name: Peripheral Nervous System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12411

- Name: Neuromuscular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M23686

- Name: Genetic Diseases, Inborn

- Relevance: LOW

- As Found: Unknown

- ID: M11641

- Name: Metabolism, Inborn Errors

- Relevance: LOW

- As Found: Unknown

- ID: T2264

- Name: Familial Transthyretin Amyloidosis

- Relevance: HIGH

- As Found: Transthyretin Amyloidosis

- ID: T340

- Name: Amyloid Neuropathy

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000028227

- Term: Amyloid Neuropathies, Familial

- ID: D000028226

- Term: Amyloidosis, Familial

- ID: D000000686

- Term: Amyloidosis

### Misc Info Module

- Version Holder: 2024-05-24

## Results Section

### Adverse Events Module

**Description:** Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).

#### Event Groups

**Group ID:** EG000

**Title:** Vutrisiran + Vutrisiran (HELIOS-A)

**Deaths Num Affected:** 2

**Deaths Num At Risk:** 122

**Description:** Participants will receive vutrisiran 25 mg SC injection q3M for 18 months during the Treatment Period followed by vutrisiran SC injection q6M or q3M during the RTE Period.

**ID:** EG000

**Other Num Affected:** 78

**Other Num at Risk:** 122

**Serious Number Affected:** 21

**Serious Number At Risk:** 122

**Title:** Vutrisiran + Vutrisiran (HELIOS-A)

**Group ID:** EG001

**Title:** Patisiran + Vutrisiran (HELIOS-A)

**Deaths Num Affected:** 3

**Deaths Num At Risk:** 42

**Description:** Participants will receive patisiran 0.3 mg/kg IV infusion q3w for 18 months during the Treatment Period followed by vutrisiran SC injection q6M or q3M during the RTE Period.

**ID:** EG001

**Other Num Affected:** 31

**Other Num at Risk:** 42

**Serious Number Affected:** 17

**Serious Number At Risk:** 42

**Title:** Patisiran + Vutrisiran (HELIOS-A)

**Frequency Threshold:** 5

#### Other Events

**Term:** Abdominal pain

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Gastrointestinal disorders

**Source Vocabulary:** MedDRA (23.0)

**Term:** Constipation

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Gastrointestinal disorders

**Source Vocabulary:** MedDRA (23.0)

**Term:** Diarrhoea

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Gastrointestinal disorders

**Source Vocabulary:** MedDRA (23.0)

**Term:** Nausea

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Gastrointestinal disorders

**Source Vocabulary:** MedDRA (23.0)

**Term:** Vomiting

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Gastrointestinal disorders

**Source Vocabulary:** MedDRA (23.0)

**Term:** Oedema peripheral

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** General disorders

**Source Vocabulary:** MedDRA (23.0)

**Term:** Infusion related reaction

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Immune system disorders

**Source Vocabulary:** MedDRA (23.0)

**Term:** Nasopharyngitis

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Infections and infestations

**Source Vocabulary:** MedDRA (23.0)

**Term:** Upper respiratory tract infection

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Infections and infestations

**Source Vocabulary:** MedDRA (23.0)

**Term:** Urinary tract infection

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Infections and infestations

**Source Vocabulary:** MedDRA (23.0)

**Term:** Fall

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Injury, poisoning and procedural complications

**Source Vocabulary:** MedDRA (23.0)

**Term:** Ligament sprain

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Injury, poisoning and procedural complications

**Source Vocabulary:** MedDRA (23.0)

**Term:** Alanine aminotransferase increased

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Investigations

**Source Vocabulary:** MedDRA (23.0)

**Term:** Aspartate aminotransferase increased

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Investigations

**Source Vocabulary:** MedDRA (23.0)

**Term:** Vitamin A decreased

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Investigations

**Source Vocabulary:** MedDRA (23.0)

**Term:** Arthralgia

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Musculoskeletal and connective tissue disorders

**Source Vocabulary:** MedDRA (23.0)

**Term:** Back pain

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Musculoskeletal and connective tissue disorders

**Source Vocabulary:** MedDRA (23.0)

**Term:** Pain in extremity

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Musculoskeletal and connective tissue disorders

**Source Vocabulary:** MedDRA (23.0)

**Term:** Dizziness

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Nervous system disorders

**Source Vocabulary:** MedDRA (23.0)

**Term:** Headache

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Nervous system disorders

**Source Vocabulary:** MedDRA (23.0)

**Term:** Neuralgia

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Nervous system disorders

**Source Vocabulary:** MedDRA (23.0)

**Term:** Rash

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Skin and subcutaneous tissue disorders

**Source Vocabulary:** MedDRA (23.0)

#### Serious Events

**Term:** Acute myocardial infarction

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Cardiac disorders

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 122

**Group ID:** EG001

**Num At Risk:** 42

**Term:** Arrhythmia

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Cardiac disorders

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num At Risk:** 122

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 42

**Term:** Atrioventricular block complete

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Cardiac disorders

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 122

**Group ID:** EG001

**Num At Risk:** 42

**Term:** Cardiac failure

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Cardiac disorders

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 122

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 42

**Term:** Cardiac failure acute

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Cardiac disorders

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 122

**Group ID:** EG001

**Num At Risk:** 42

**Term:** Cardiac failure chronic

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Cardiac disorders

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 122

**Group ID:** EG001

**Num At Risk:** 42

**Term:** Cardiac failure congestive

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Cardiac disorders

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 122

**Group ID:** EG001

**Num Affected:** 2

**Num At Risk:** 42

**Term:** Cardiogenic shock

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Cardiac disorders

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num At Risk:** 122

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 42

**Term:** Conduction disorder

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Cardiac disorders

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 122

**Group ID:** EG001

**Num At Risk:** 42

**Term:** Myocardial ischaemia

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Cardiac disorders

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 122

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 42

**Term:** Ventricular tachycardia

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Cardiac disorders

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 122

**Group ID:** EG001

**Num At Risk:** 42

**Term:** Vertigo

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Ear and labyrinth disorders

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num At Risk:** 122

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 42

**Term:** Cyclic vomiting syndrome

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Gastrointestinal disorders

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num At Risk:** 122

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 42

**Term:** Diarrhoea

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Gastrointestinal disorders

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num At Risk:** 122

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 42

**Term:** Upper gastrointestinal haemorrhage

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Gastrointestinal disorders

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 122

**Group ID:** EG001

**Num At Risk:** 42

**Term:** Asthenia

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** General disorders

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 122

**Group ID:** EG001

**Num At Risk:** 42

**Term:** Infusion site phlebitis

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** General disorders

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num At Risk:** 122

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 42

**Term:** Infusion related reaction

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Immune system disorders

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num At Risk:** 122

**Group ID:** EG001

**Num Affected:** 3

**Num At Risk:** 42

**Term:** COVID-19

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Infections and infestations

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num Affected:** 2

**Num At Risk:** 122

**Group ID:** EG001

**Num At Risk:** 42

**Term:** COVID-19 pneumonia

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Infections and infestations

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num Affected:** 2

**Num At Risk:** 122

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 42

**Term:** Endocarditis

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Infections and infestations

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num At Risk:** 122

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 42

**Term:** Escherichia urinary tract infection

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Infections and infestations

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 122

**Group ID:** EG001

**Num At Risk:** 42

**Term:** Infusion site cellulitis

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Infections and infestations

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num At Risk:** 122

**Group ID:** EG001

**Num Affected:** 2

**Num At Risk:** 42

**Term:** Kidney infection

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Infections and infestations

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 122

**Group ID:** EG001

**Num At Risk:** 42

**Term:** Pneumonia

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Infections and infestations

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num Affected:** 2

**Num At Risk:** 122

**Group ID:** EG001

**Num At Risk:** 42

**Term:** Pyelonephritis

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Infections and infestations

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 122

**Group ID:** EG001

**Num At Risk:** 42

**Term:** Sepsis

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Infections and infestations

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num Affected:** 2

**Num At Risk:** 122

**Group ID:** EG001

**Num At Risk:** 42

**Term:** Urinary tract infection

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Infections and infestations

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num At Risk:** 122

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 42

**Term:** Vestibular neuronitis

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Infections and infestations

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num At Risk:** 122

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 42

**Term:** Fall

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Injury, poisoning and procedural complications

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num Affected:** 2

**Num At Risk:** 122

**Group ID:** EG001

**Num At Risk:** 42

**Term:** Femur fracture

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Injury, poisoning and procedural complications

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 122

**Group ID:** EG001

**Num At Risk:** 42

**Term:** Foot fracture

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Injury, poisoning and procedural complications

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num At Risk:** 122

**Group ID:** EG001

**Num Affected:** 2

**Num At Risk:** 42

**Term:** Fractured sacrum

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Injury, poisoning and procedural complications

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 122

**Group ID:** EG001

**Num At Risk:** 42

**Term:** Post procedural complication

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Injury, poisoning and procedural complications

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 122

**Group ID:** EG001

**Num At Risk:** 42

**Term:** Cardiovascular evaluation

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Investigations

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num At Risk:** 122

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 42

**Term:** Investigation

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Investigations

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num At Risk:** 122

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 42

**Term:** Dyslipidaemia

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Metabolism and nutrition disorders

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 122

**Group ID:** EG001

**Num At Risk:** 42

**Term:** Fluid overload

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Metabolism and nutrition disorders

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num At Risk:** 122

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 42

**Term:** Hypokalaemia

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Metabolism and nutrition disorders

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 122

**Group ID:** EG001

**Num At Risk:** 42

**Term:** Endometrial neoplasm

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps)

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 122

**Group ID:** EG001

**Num At Risk:** 42

**Term:** Cerebrovascular accident

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Nervous system disorders

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num At Risk:** 122

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 42

**Term:** Dizziness

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Nervous system disorders

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 122

**Group ID:** EG001

**Num At Risk:** 42

**Term:** Neuralgia

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Nervous system disorders

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 122

**Group ID:** EG001

**Num At Risk:** 42

**Term:** Syncope

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Nervous system disorders

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 122

**Group ID:** EG001

**Num At Risk:** 42

**Term:** Acute kidney injury

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Renal and urinary disorders

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 122

**Group ID:** EG001

**Num At Risk:** 42

**Term:** Renal failure

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Renal and urinary disorders

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 122

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 42

**Term:** Hospitalisation

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Surgical and medical procedures

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num At Risk:** 122

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 42

**Term:** Hypotension

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Vascular disorders

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 122

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 42

**Term:** Iliac artery occlusion

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Vascular disorders

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 122

**Group ID:** EG001

**Num At Risk:** 42

**Term:** Orthostatic hypotension

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Vascular disorders

**Source Vocabulary:** MedDRA (23.0)

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 122

**Group ID:** EG001

**Num At Risk:** 42

**Time Frame:** Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9.

## Results Section - Baseline Characteristics Module

### Denomination Counts

**Group ID:** BG000

**Value:** 77

**Group ID:** BG001

**Value:** 122

**Group ID:** BG002

**Value:** 42

**Group ID:** BG003

**Value:** 241

**Units:** Participants

### Group

**ID:** BG000

**Title:** External Placebo Comparator (APOLLO)

**Description:** Participants in the APOLLO study (NCT01960348) who received at least 1 dose of placebo.

### Group

**ID:** BG001

**Title:** Vutrisiran + Vutrisiran (HELIOS-A)

**Description:** Participants will receive vutrisiran 25 mg SC injection q3M for 18 months during the Treatment Period followed by vutrisiran SC injection q6M or q3M during the RTE Period.

### Group

**ID:** BG002

**Title:** Patisiran + Vutrisiran (HELIOS-A)

**Description:** Participants will receive patisiran 0.3 mg/kg IV infusion q3w for 18 months during the Treatment Period followed by vutrisiran SC injection q6M or q3M during the RTE Period.

### Group

**ID:** BG003

**Title:** Total

**Description:** Total of all reporting groups

### Measure

#### Measurement

**Group ID:** BG001

**Spread:** 13.2

**Value:** 57.8

#### Measurement

**Group ID:** BG002

**Spread:** 10.5

**Value:** 58.0

#### Measurement

**Group ID:** BG003

**Spread:** 12.5

**Value:** 57.9

#### Denomination

**Units:** Participants

##### Denomination Counts

**Group ID:** BG000

**Value:** 0

**Group ID:** BG001

**Value:** 122

**Group ID:** BG002

**Value:** 42

**Group ID:** BG003

**Value:** 164

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 10.76

**Value:** 62.2

#### Measurement

**Group ID:** BG003

**Spread:** 10.76

**Value:** 62.2

#### Denomination

**Units:** Participants

##### Denomination Counts

**Group ID:** BG000

**Value:** 77

**Group ID:** BG001

**Value:** 0

**Group ID:** BG002

**Value:** 0

**Group ID:** BG003

**Value:** 77

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG001

**Value:** 43

#### Measurement

**Group ID:** BG002

**Value:** 15

#### Measurement

**Group ID:** BG003

**Value:** 58

**Category Title:** Female

#### Measurement

**Group ID:** BG001

**Value:** 79

#### Measurement

**Group ID:** BG002

**Value:** 27

#### Measurement

**Group ID:** BG003

**Value:** 106

**Category Title:** Male

#### Denomination

**Units:** Participants

##### Denomination Counts

**Group ID:** BG000

**Value:** 0

**Group ID:** BG001

**Value:** 122

**Group ID:** BG002

**Value:** 42

**Group ID:** BG003

**Value:** 164

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 19

#### Measurement

**Group ID:** BG003

**Value:** 19

**Category Title:** Female

#### Measurement

**Group ID:** BG000

**Value:** 58

#### Measurement

**Group ID:** BG003

**Value:** 58

**Category Title:** Male

#### Denomination

**Units:** Participants

##### Denomination Counts

**Group ID:** BG000

**Value:** 77

**Group ID:** BG001

**Value:** 0

**Group ID:** BG002

**Value:** 0

**Group ID:** BG003

**Value:** 77

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 0

#### Measurement

**Group ID:** BG001

**Value:** 21

#### Measurement

**Group ID:** BG002

**Value:** 8

#### Measurement

**Group ID:** BG003

**Value:** 29

#### Denomination

**Units:** Participants

##### Denomination Counts

**Group ID:** BG000

**Value:** 0

**Group ID:** BG001

**Value:** 122

**Group ID:** BG002

**Value:** 42

**Group ID:** BG003

**Value:** 164

**Class Title:** Asian

#### Measurement

**Group ID:** BG000

**Value:** 0

#### Measurement

**Group ID:** BG001

**Value:** 4

#### Measurement

**Group ID:** BG002

**Value:** 4

#### Measurement

**Group ID:** BG003

**Value:** 8

#### Denomination

**Units:** Participants

##### Denomination Counts

**Group ID:** BG000

**Value:** 0

**Group ID:** BG001

**Value:** 122

**Group ID:** BG002

**Value:** 42

**Group ID:** BG003

**Value:** 164

**Class Title:** Black or African American

#### Measurement

**Group ID:** BG000

**Value:** 0

#### Measurement

**Group ID:** BG001

**Value:** 1

#### Measurement

**Group ID:** BG002

**Value:** 0

#### Measurement

**Group ID:** BG003

**Value:** 1

#### Denomination

**Units:** Participants

##### Denomination Counts

**Group ID:** BG000

**Value:** 0

**Group ID:** BG001

**Value:** 122

**Group ID:** BG002

**Value:** 42

**Group ID:** BG003

**Value:** 164

**Class Title:** Multiple

#### Measurement

**Group ID:** BG000

**Value:** 0

#### Measurement

**Group ID:** BG001

**Value:** 10

#### Measurement

**Group ID:** BG002

**Value:** 1

#### Measurement

**Group ID:** BG003

**Value:** 11

#### Denomination

**Units:** Participants

##### Denomination Counts

**Group ID:** BG000

**Value:** 0

**Group ID:** BG001

**Value:** 122

**Group ID:** BG002

**Value:** 42

**Group ID:** BG003

**Value:** 164

**Class Title:** Other

#### Measurement

**Group ID:** BG000

**Value:** 0

#### Measurement

**Group ID:** BG001

**Value:** 0

#### Measurement

**Group ID:** BG002

**Value:** 0

#### Measurement

**Group ID:** BG003

**Value:** 0

#### Denomination

**Units:** Participants

##### Denomination Counts

**Group ID:** BG000

**Value:** 0

**Group ID:** BG001

**Value:** 122

**Group ID:** BG002

**Value:** 42

**Group ID:** BG003

**Value:** 164

**Class Title:** Unknown

#### Measurement

**Group ID:** BG000

**Value:** 0

#### Measurement

**Group ID:** BG001

**Value:** 86

#### Measurement

**Group ID:** BG002

**Value:** 29

#### Measurement

**Group ID:** BG003

**Value:** 115

#### Denomination

**Units:** Participants

##### Denomination Counts

**Group ID:** BG000

**Value:** 0

**Group ID:** BG001

**Value:** 122

**Group ID:** BG002

**Value:** 42

**Group ID:** BG003

**Value:** 164

**Class Title:** White

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 25

#### Measurement

**Group ID:** BG003

**Value:** 25

#### Denomination

**Units:** Participants

##### Denomination Counts

**Group ID:** BG000

**Value:** 77

**Group ID:** BG001

**Value:** 0

**Group ID:** BG002

**Value:** 0

**Group ID:** BG003

**Value:** 77

**Class Title:** Asian

#### Measurement

**Group ID:** BG000

**Value:** 1

#### Measurement

**Group ID:** BG003

**Value:** 1

#### Denomination

**Units:** Participants

##### Denomination Counts

**Group ID:** BG000

**Value:** 77

**Group ID:** BG001

**Value:** 0

**Group ID:** BG002

**Value:** 0

**Group ID:** BG003

**Value:** 77

**Class Title:** Black or African American

#### Measurement

**Group ID:** BG000

**Value:** 50

#### Measurement

**Group ID:** BG003

**Value:** 50

#### Denomination

**Units:** Participants

##### Denomination Counts

**Group ID:** BG000

**Value:** 77

**Group ID:** BG001

**Value:** 0

**Group ID:** BG002

**Value:** 0

**Group ID:** BG003

**Value:** 77

**Class Title:** White

#### Measurement

**Group ID:** BG000

**Value:** 1

#### Measurement

**Group ID:** BG003

**Value:** 1

#### Denomination

**Units:** Participants

##### Denomination Counts

**Group ID:** BG000

**Value:** 77

**Group ID:** BG001

**Value:** 0

**Group ID:** BG002

**Value:** 0

**Group ID:** BG003

**Value:** 77

**Class Title:** Unknown or Not Reported

### Measure

#### Measurement

**Group ID:** BG001

**Spread:** 35.99

**Value:** 60.55

#### Measurement

**Group ID:** BG002

**Spread:** 33.71

**Value:** 57.69

#### Measurement

**Group ID:** BG003

**Spread:** 35.34

**Value:** 59.82

#### Denomination

**Units:** Participants

##### Denomination Counts

**Group ID:** BG000

**Value:** 0

**Group ID:** BG001

**Value:** 122

**Group ID:** BG002

**Value:** 42

**Group ID:** BG003

**Value:** 164

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 37.041

**Value:** 74.61

#### Measurement

**Group ID:** BG003

**Spread:** 37.041

**Value:** 74.61

#### Denomination

**Units:** Participants

##### Denomination Counts

**Group ID:** BG000

**Value:** 77

**Group ID:** BG001

**Value:** 0

**Group ID:** BG002

**Value:** 0

**Group ID:** BG003

**Value:** 77

**Class Title:** 

**Denomination Units Selected:** 

## Results Section - Baseline Characteristics Module

### Measure 1
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Population Description:** Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately directly below.
**Title:** Age, Continuous
**Unit of Measure:** years
### Measure 2
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Population Description:** Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately.
**Title:** Age, Continuous
**Unit of Measure:** years
### Measure 3
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Population Description:** Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately directly below.
**Title:** Sex: Female, Male
**Unit of Measure:** Participants
### Measure 4
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Population Description:** Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately.
**Title:** Sex: Female, Male
**Unit of Measure:** Participants
### Measure 5
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Population Description:** Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately directly below.
**Title:** Race/Ethnicity, Customized
**Unit of Measure:** Participants
### Measure 6
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Population Description:** Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately.
**Title:** Race/Ethnicity, Customized
**Unit of Measure:** Participants
### Measure 7
**Description:** The mNIS+7 is a composite score that measures neurologic impairment which includes the following components: physical exam of lower limbs, upper limbs and cranial nerves to assess motor strength/weakness, electrophysiologic measurement of small and large nerve fiber function, sensory testing and postural blood pressure. The mNIS+7 is scored from 0 (no impairment) to 304 points (maximum impairment). A higher score indicates a worse outcome.
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Population Description:** Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately directly below.
**Title:** Modified Neuropathy Impairment Score +7 (mNIS+7)
**Unit of Measure:** score on a scale
### Measure 8
**Description:** The mNIS+7 is a composite score that measures neurologic impairment which includes the following components: physical exam of lower limbs, upper limbs and cranial nerves to assess motor strength/weakness, electrophysiologic measurement of small and large nerve fiber function, sensory testing and postural blood pressure. The mNIS+7 is scored from 0 (no impairment) to 304 points (maximum impairment). A higher score indicates a worse outcome.
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Population Description:** Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately.
**Title:** Modified Neuropathy Impairment Score +7 (mNIS+7)
**Unit of Measure:** score on a scale
**Population Description:** Safety Population: all participants who received any amount of study drug. Data from the placebo arm of the APOLLO study (NCT01960348) is included as it will be used as an external comparator for the primary and most other efficacy endpoints. The placebo APOLLO arm did not participate in this study.
## Results Section - More Information Module
### Certain Agreement
**Other Details:** It is intended that after completion of the study, the data are to be submitted for publication in a scientific journal and/or for reporting at a scientific meeting. A copy of any proposed publication (eg, manuscript, abstracts, oral/slide presentations, book chapters) based on this study, must be provided and confirmed/received at the Sponsor at least 30 days before its submission.
**Restriction Type:** OTHER
**Restrictive Agreement:** True
### Point of Contact
**Email:** clinicaltrials@alnylam.com
**Organization:** Alnylam Pharmaceuticals Inc.
**Phone:** 866-330-0326
**Title:** Chief Medical Officer
## Results Section - Outcome Measures Module
### Outcome Measure 1
#### Analysis
**CI Lower Limit:** -21.78
**CI Number of Sides:** TWO_SIDED
**CI Percentage Value:** 95
**CI Upper Limit:** -12.22
**CI Upper Limit Comment:** 
**Dispersion Type:** STANDARD_ERROR_OF_MEAN
**Dispersion Value:** 2.44
**Estimate Comment:** 
**Group Description:** Multiple imputation estimates and p-value derived per combining least squares (LS) estimates per Rubin's rules based on 100 datasets where missing Month 9 values were imputed using a regression procedure including select baseline variables. LS estimates derived from analysis of covariance model, controlling for categorical factors (treatment, genotype, age of disease onset) and continuous covariate (baseline value).
**Non-Inferiority Comment:** H0: No difference between vutrisiran and external placebo comparator (APOLLO): difference (vutrisiran - placebo) = 0
**Non-Inferiority Type:** EQUIVALENCE
**Other Analysis Description:** 
**P-Value:** <0.0000001
**P-Value Comment:** P=3.542E-12
**Parameter Type:** LS Mean Difference
**Parameter Value:** -17.00
**Statistical Comment:** 
**Statistical Method:** ANCOVA with Multiple Imputation
**Tested Non-Inferiority:** 
### Outcome Measure 2
#### Analysis
**CI Lower Limit:** -21.7
**CI Number of Sides:** TWO_SIDED
**CI Percentage Value:** 95
**CI Upper Limit:** -10.8
**CI Upper Limit Comment:** 
**Dispersion Type:** STANDARD_ERROR_OF_MEAN
**Dispersion Value:** 2.8
**Estimate Comment:** 
**Group Description:** Multiple imputation estimates and p-value derived per combining least squares (LS) estimates per Rubin's rules based on 100 datasets where missing Month 9 values were imputed using a regression procedure including select baseline variables. LS estimates derived from analysis of covariance model, controlling for categorical factors (treatment, genotype, age of disease onset baseline NIS) and continuous covariate (baseline value).
**Non-Inferiority Comment:** H0: No difference between vutrisiran and external placebo comparator (APOLLO): difference (vutrisiran - placebo) = 0
**Non-Inferiority Type:** EQUIVALENCE
**Other Analysis Description:** 
**P-Value:** <0.0000001
**P-Value Comment:** P=5.426E-09
**Parameter Type:** LS Mean Difference
**Parameter Value:** -16.2
**Statistical Comment:** 
**Statistical Method:** ANCOVA with Multiple Imputation
**Tested Non-Inferiority:** 
### Outcome Measure 3
#### Analysis
**CI Lower Limit:** 0.070
**CI Number of Sides:** TWO_SIDED
**CI Percentage Value:** 95
**CI Upper Limit:** 0.193
**CI Upper Limit Comment:** 
**Dispersion Type:** STANDARD_ERROR_OF_MEAN
**Dispersion Value:** 0.031
**Estimate Comment:** 
**Group Description:** Multiple imputation estimates and p-value derived per combining least squares (LS) estimates per Rubin's rules based on 100 datasets where missing Month 9 values were imputed using a regression procedure including select baseline variables. LS estimates derived from analysis of covariance model, controlling for categorical factors (treatment, genotype, age of disease onset, baseline NIS) and continuous covariate (baseline value).
**Non-Inferiority Comment:** H0: No difference between vutrisiran and external placebo comparator (APOLLO): difference (vutrisiran - placebo) = 0
**Non-Inferiority Type:** EQUIVALENCE
**Other Analysis Description:** 
**P-Value:** <0.0000001
**P-Value Comment:** P=3.103E-05
**Parameter Type:** LS Mean Difference
**Parameter Value:** 0.131
**Statistical Comment:** 
**Statistical Method:** ANCOVA with Multiple Imputation
**Tested Non-Inferiority:** 
### Outcome Measure 4
### Outcome Measure 5
### Outcome Measure 6
### Outcome Measure 7
### Outcome Measure 8
### Outcome Measure 9
## Results Section
### Outcome Measures Module
#### Outcome Measure 1
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 2.00
- **Upper Limit:** 
- **Value:** 14.76
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 1.43
- **Upper Limit:** 
- **Value:** -2.24
**Title:** 
#### Outcome Measure 2
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 2.2
- **Upper Limit:** 
- **Value:** 12.9
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 1.7
- **Upper Limit:** 
- **Value:** -3.3
**Title:** 
#### Outcome Measure 3
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 0.025
- **Upper Limit:** 
- **Value:** -0.133
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 0.019
- **Upper Limit:** 
- **Value:** -0.001
**Title:** 
#### Outcome Measure 4
#### Outcome Measure 5
#### Outcome Measure 6
#### Outcome Measure 7
#### Outcome Measure 8
#### Outcome Measure 9
## Results Section
### Outcome Measures Module
#### Outcome Measure 1
**Description:** The mNIS+7 is a composite score that measures neurologic impairment which includes the following components: physical exam of lower limbs, upper limbs and cranial nerves to assess motor strength/weakness, electrophysiologic measurement of small and large nerve fiber function, sensory testing and postural blood pressure. The mNIS+7 is scored from 0 (no impairment) to 304 points (maximum impairment). A higher score indicates a worse outcome.
**Dispersion Type:** Standard Error
**Parameter Type:** LEAST_SQUARES_MEAN
**Population Description:** Modified Intent-to-Treat (mITT) Population: All randomized participants who received any amount of study drug. Participants were analyzed according to the treatment to which they were randomized.
**Reporting Status:** POSTED
**Time Frame:** Baseline, Month 9
**Title:** Change From Baseline in the Modified Neurologic Impairment Score +7 (mNIS+7) at Month 9 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)]
**Type:** PRIMARY
**Unit of Measure:** score on a scale
##### Group
**Description:** Participants in the APOLLO study (NCT01960348) who received at least 1 dose of placebo.
**ID:** OG000
**Title:** External Placebo Comparator (APOLLO)
##### Group
**Description:** Participants will receive vutrisiran 25 mg subcutaneous (SC) injection once every 3 months (q3M) for 18 months during the Treatment Period followed by vutrisiran SC injection during the Randomized Treatment Extension (RTE) Period.
**ID:** OG001
**Title:** Vutrisiran + Vutrisiran (HELIOS-A)
#### Outcome Measure 2
**Description:** The Norfolk QoL-DN questionnaire is a standardized 35-item patient-reported outcomes measure that is sensitive to the different features of diabetic neuropathy - small fiber, large fiber, and autonomic nerve function. The total score ranges from -4 (best possible quality of life) to 136 points (worst possible quality of life). A higher score indicates a worse outcome.
**Dispersion Type:** Standard Error
**Parameter Type:** LEAST_SQUARES_MEAN
**Population Description:** Modified Intent-to-Treat (mITT) Population: All randomized participants who received any amount of study drug. Participants were analyzed according to the treatment to which they were randomized.
**Reporting Status:** POSTED
**Time Frame:** Baseline, Month 9
**Title:** Change From Baseline in Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) Total Score at Month 9 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)]
**Type:** SECONDARY
**Unit of Measure:** score on a scale
##### Group
**Description:** Participants in the APOLLO study (NCT01960348) who received at least 1 dose of placebo.
**ID:** OG000
**Title:** External Placebo Comparator (APOLLO)
##### Group
**Description:** Participants will receive vutrisiran 25 mg subcutaneous (SC) injection once every 3 months (q3M) for 18 months during the Treatment Period followed by vutrisiran SC injection during the Randomized Treatment Extension (RTE) Period.
**ID:** OG001
**Title:** Vutrisiran + Vutrisiran (HELIOS-A)
#### Outcome Measure 3
**Description:** The 10-MWT is a measure of ambulatory ability and measures the time (in seconds) that it takes a participant to walk 10 meters (gait speed). An increase in gait speed from baseline represents improvement, and a decrease from baseline represents worsening.
**Dispersion Type:** Standard Error
**Parameter Type:** LEAST_SQUARES_MEAN
**Population Description:** Modified Intent-to-Treat (mITT) Population: All randomized participants who received any amount of study drug. Participants were analyzed according to the treatment to which they were randomized.
**Reporting Status:** POSTED
**Time Frame:** Baseline, Month 9
**Title:** Change From Baseline in the Timed 10-Meter Walk Test (10-MWT) at Month 9 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)]
**Type:** SECONDARY
**Unit of Measure:** m/sec
##### Group
**Description:** Participants in the APOLLO study (NCT01960348) who received at least 1 dose of placebo.
**ID:** OG000
**Title:** External Placebo Comparator (APOLLO)
##### Group
**Description:** Participants will receive vutrisiran 25 mg subcutaneous (SC) injection once every 3 months (q3M) for 18 months during the Treatment Period followed by vutrisiran SC injection during the Randomized Treatment Extension (RTE) Period.
**ID:** OG001
**Title:** Vutrisiran + Vutrisiran (HELIOS-A)
#### Outcome Measure 4
**Description:** The mNIS+7 is a composite score that quantifies motor, sensory, and autonomic neurologic impairment due to injury of large and small nerves. The mNIS+7 is scored from 0 (no impairment) to 304 points (maximum impairment). A higher score indicates a worse outcome.
**Reporting Status:** NOT_POSTED
**Time Frame:** Baseline, Month 18
**Title:** Change From Baseline in the Modified Neurologic Impairment Score +7 (mNIS+7) at Month 18 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)]
**Type:** SECONDARY
#### Outcome Measure 5
**Description:** The Norfolk QoL-DN questionnaire is a standardized 35-item patient-reported outcomes measure that is sensitive to the different features of diabetic neuropathy - small fiber, large fiber, and autonomic nerve function. The total score ranges from -4 (best possible quality of life) to 136 points (worst possible quality of life). A higher score indicates a worse outcome.
**Reporting Status:** NOT_POSTED
**Time Frame:** Baseline, Month 18
**Title:** Change From Baseline in Norfolk QoL-DN Total Score at Month 18 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)]
**Type:** SECONDARY
#### Outcome Measure 6
**Description:** The 10-MWT is a measure of ambulatory ability and measures the time (in seconds) that it takes a participant to walk 10 meters (gait speed). An increase in gait speed from baseline represents improvement, and a decrease from baseline represents worsening.
**Reporting Status:** NOT_POSTED
**Time Frame:** Baseline, Month 18
**Title:** Change From Baseline in the 10-MWT at Month 18 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)]
**Type:** SECONDARY
#### Outcome Measure 7
**Description:** The mBMI, which is a measure of nutritional status, is calculated as the product of body mass index (BMI) (weight in kilograms divided by the square of height in meters) and serum albumin (g/L) to reflect fluid balance, such as fluid accumulation or dehydration. A negative change from baseline indicates a better outcome.
**Reporting Status:** NOT_POSTED
**Time Frame:** Baseline, Month 18
**Title:** Change From Baseline in the Modified Body Mass Index (mBMI) at Month 18 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)]
**Type:** SECONDARY
#### Outcome Measure 8
**Description:** The R-ODS is a patient-reported measure of level of disability on a scale of 0-48, with 0 being the worst and 48 the best (no limitations); scores are based on activities of daily living and social participation. An increase in R-ODS from baseline suggests improvement in disability, and a decrease from baseline suggests worsening of disability.
**Reporting Status:** NOT_POSTED
**Time Frame:** Baseline, Month 18
**Title:** Change From Baseline in the Rasch-Built Overall Disability Scale (R-ODS) at Month 18 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)]
**Type:** SECONDARY
#### Outcome Measure 9
**Description:** Serum TTR was assessed at multiple timepoints up to Month 18.
**Reporting Status:** NOT_POSTED
**Time Frame:** Up to Month 18
**Title:** Percent Reduction in Serum Transthyretin (TTR) Levels Through Month 18 Between the Vutrisiran Group (HELIOS-A) and the Patisiran Group (HELIOS-A)
**Type:** SECONDARY
### Participant Flow Module
#### Group
**Description:** Participants will receive vutrisiran 25 mg subcutaneous (SC) injection once every 3 months (q3M) for 18 months during the Treatment Period followed by vutrisiran SC injection once every 6 months (q6M) or q3M during the Randomized Treatment Extension (RTE) Period.
**ID:** FG000
**Title:** Vutrisiran + Vutrisiran (HELIOS-A)
#### Group
**Description:** Participants will receive patisiran 0.3 mg/kg intravenous (IV) infusion once every 3 weeks (q3w) for 18 months during the Treatment Period followed by vutrisiran SC injection q6M or q3M during the RTE Period.
**ID:** FG001
**Title:** Patisiran + Vutrisiran (HELIOS-A)
#### Period
**Title:** Treatment Period
##### Withdraw
**Type:** Remained in this Period at Time of Data Cut
###### Reason
**Group ID:** FG000
**Number of Subjects:** 119
###### Reason
**Group ID:** FG001
**Number of Subjects:** 38
##### Withdraw
**Type:** Death
###### Reason
**Group ID:** FG000
**Number of Subjects:** 2
###### Reason
**Group ID:** FG001
**Number of Subjects:** 3
##### Withdraw
**Type:** Lost to Follow-up
###### Reason
**Group ID:** FG000
**Number of Subjects:** 1
###### Reason
**Group ID:** FG001
**Number of Subjects:** 0
##### Withdraw
**Type:** Physician Decision
###### Reason
**Group ID:** FG000
**Number of Subjects:** 0
###### Reason
**Group ID:** FG001
**Number of Subjects:** 1
##### Milestone
**Type:** STARTED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 122
###### Achievement
**Group ID:** FG001
**Number of Subjects:** 42
##### Milestone
**Type:** COMPLETED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 0
###### Achievement
**Group ID:** FG001
**Number of Subjects:** 0
##### Milestone
**Type:** NOT COMPLETED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 122
###### Achievement
**Group ID:** FG001
**Number of Subjects:** 42
#### Period
**Title:** Randomized Treatment Extension Period
##### Milestone
**Type:** STARTED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 0
###### Achievement
**Group ID:** FG001
**Number of Subjects:** 0
##### Milestone
**Type:** COMPLETED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 0
###### Achievement
**Group ID:** FG001
**Number of Subjects:** 0
##### Milestone
**Type:** NOT COMPLETED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 0
###### Achievement
**Group ID:** FG001
**Number of Subjects:** 0
**Pre-Assignment Details:** This study will use the placebo arm of the APOLLO study (NCT01960348) as an external comparator for the primary and most other efficacy endpoints (N=77).
**Recruitment Details:** Participants with hATTR amyloidosis were enrolled and treated at 57 sites in Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, Cyprus, France, Germany, Greece, Italy, Japan, Korea, Malaysia, Mexico, Netherlands, Portugal, Spain, Sweden, Taiwan, United Kingdom and United States. Data is reported for the 9-Month primary analysis period.
**Has Results:** True