## Protocol Section
### Identification Module
**NCT ID:** NCT06421636

**Acronym:** FERVENT-1

**Brief Title:** A Study to Test the Safety, Tolerability, and Efficacy of an Antibody, REGN7999, Injected Under the Skin for the Treatment of Iron Overload in Adult Participants With Non-Transfusion Dependent β-thalassemia, Using MRI Scans to Measure Iron Levels in the Body

**Official Title:** A PHASE 2, TWO-PART, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY TO EVALUATE THE EFFICACY, SAFETY, AND TOLERABILITY OF SUBCUTANEOUSLY ADMINISTERED REGN7999 (AN INHIBITOR OF TMPRSS6) IN PARTICIPANTS WITH IRON OVERLOAD DUE TO NON-TRANSFUSION DEPENDENT β-THALASSEMIA

#### Organization Study ID Info
**ID:** R7999-BThal-2350
#### Organization
**Class:** INDUSTRY
**Full Name:** Regeneron Pharmaceuticals
#### Secondary ID Infos
**Domain:** EU CT Number
**ID:** 2023-508604-37-00
**Type:** OTHER
### Status Module
#### Completion Date
**Date:** 2028-01-24

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-20

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-14

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2028-01-24

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-09-25

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-20
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-14
**Study First Submit QC Date:** 2024-05-14
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Regeneron Pharmaceuticals

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** This study is researching an experimental drug called REGN7999 (called "study drug"). The study is focused on patients with non-transfusion dependent beta-thalassemia. The aim of the study is to see how safe and effective the study drug is.

The study is looking at several other research questions, including:

* Whether the study drug lowers extra iron levels in the body
* What side effects may happen from taking the study drug
* How much study drug is in the blood at different times
* Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects)

### Conditions Module

**Conditions:**

- Non-transfusion Dependent Beta-thalassemia (NTDT)

**Keywords:**

- Beta-thalassemia

- Resultant Iron overload (IOL)

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** QUADRUPLE

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 95

**Type:** ESTIMATED

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Randomized 2:2:1

**Intervention Names:**

- Drug: REGN7999

**Label:** Part A High Dose

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Randomized 2:2:1

**Intervention Names:**

- Drug: REGN7999

**Label:** Part A Low Dose

**Type:** EXPERIMENTAL

#### Arm Group 3

**Description:** Randomized 2:2:1

**Intervention Names:**

- Drug: Placebo

**Label:** Part A Placebo

**Type:** PLACEBO_COMPARATOR

#### Arm Group 4

**Description:** Randomized 2:2:1

**Intervention Names:**

- Drug: REGN7999

**Label:** Part B High Dose

**Type:** EXPERIMENTAL

#### Arm Group 5

**Description:** Randomized 2:2:1

**Intervention Names:**

- Drug: REGN7999

**Label:** Part B Low Dose

**Type:** EXPERIMENTAL

#### Arm Group 6

**Description:** Randomized 2:2:1

**Intervention Names:**

- Drug: Placebo

**Label:** Part B Placebo

**Type:** PLACEBO_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Part A High Dose

- Part A Low Dose

- Part B High Dose

- Part B Low Dose

**Description:** Administered subcutaneous (SC)

**Name:** REGN7999

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Part A Placebo

- Part B Placebo

**Description:** Administered SC

**Name:** Placebo

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Measure:** Change in Liver iron concentration (LIC) by R2* magnetic resonance imaging (MRI)

**Time Frame:** Baseline to week 24

**Measure:** Incidence of Treatment-emergent adverse events (TEAEs)

**Time Frame:** Up to week 72

**Measure:** Severity of Treatment-emergent adverse events (TEAEs)

**Time Frame:** Up to week 72

#### Secondary Outcomes

**Measure:** Achievement of ≥20% reduction in LIC by R2* MRI

**Time Frame:** Baseline to week 52

**Measure:** Change in hemoglobin

**Time Frame:** Baseline to week 24

**Measure:** Change in LIC by R2* MRI

**Time Frame:** Baseline to week 52

**Measure:** Percent change in LIC by R2* MRI

**Time Frame:** Baseline to week 24 and week 52

**Measure:** Achievement of ≥20% reduction in LIC by R2* MRI

**Time Frame:** Baseline to week 24

**Measure:** Change in hemoglobin over time

**Time Frame:** Up to week 56

**Measure:** Achievement of ≥1.5 g/dL increase in hemoglobin for two consecutive assessments in the absence of red blood cell (RBC) transfusions

**Time Frame:** Baseline to week 56

**Measure:** Number of RBC transfusions required

**Time Frame:** Baseline to week 72

**Measure:** Achievement of transfusion independence

**Time Frame:** Baseline to week 72

**Measure:** Change in RBC counts over time

**Time Frame:** Baseline to week 56

**Measure:** Concentrations of REGN7999 in serum over time

**Time Frame:** Up to week 56

**Measure:** Incidence of anti-drug antibody (ADA) to REGN7999 over time

**Time Frame:** Up to week 56

**Measure:** Titer of ADA to REGN7999 over time

**Time Frame:** Up to week 56

### Eligibility Module

**Eligibility Criteria:** Key Inclusion Criteria:

1. Clinical diagnosis of NTDT as described in the protocol
2. IOL, defined as LIC ≥ 5 mg Fe/g DW as measured by R2\* MRI at screening
3. Serum ferritin ≥ 300 ng/mL as described in the protocol

Key Exclusion Criteria:

1. Hemoglobin ≤ 8 g/dL
2. Any RBC transfusion within approximately 8 weeks prior to screening as described in the protocol
3. For Part A only: Any ICT use in approximately 12 weeks prior to screening as described in the protocol
4. For Part B only: If on ICT, any change in Iron chelation therapy (ICT) dose in approximately 12 weeks prior to screening as described in the protocol
5. Any use of luspatercept or mitapivat in 6 months prior to screening as described in the protocol
6. Absolute contraindication to MRI

Note: Other protocol-defined Inclusion/ Exclusion Criteria apply

**Maximum Age:** 60 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** clinicaltrials@regeneron.com

**Name:** Clinical Trials Administrator

**Phone:** 844-734-6643

**Role:** CONTACT

#### Overall Officials

**Official 1:**

**Affiliation:** Regeneron Pharmaceuticals

**Name:** Clinical Trial Management

**Role:** STUDY_DIRECTOR

### IPD Sharing Statement Module

**Access Criteria:** Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf

**Description:** All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.

**Info Types:**

- STUDY_PROTOCOL

- SAP

- ICF

- CSR

- ANALYTIC_CODE

**IPD Sharing:** YES

**Time Frame:** When Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication, has made results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has ensured the ability to protect participant privacy.

**URL:** https://vivli.org/

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000000745

- Term: Anemia, Hemolytic, Congenital

- ID: D000000743

- Term: Anemia, Hemolytic

- ID: D000000740

- Term: Anemia

- ID: D000006402

- Term: Hematologic Diseases

- ID: D000006453

- Term: Hemoglobinopathies

- ID: D000030342

- Term: Genetic Diseases, Inborn

- ID: D000019189

- Term: Iron Metabolism Disorders

- ID: D000008659

- Term: Metabolic Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC15

- Name: Blood and Lymph Conditions

- Abbrev: BC16

- Name: Diseases and Abnormalities at or Before Birth

- Abbrev: All

- Name: All Conditions

- Abbrev: BC18

- Name: Nutritional and Metabolic Diseases

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M16557

- Name: Thalassemia

- Relevance: HIGH

- As Found: Thalassemia

- ID: M19408

- Name: beta-Thalassemia

- Relevance: HIGH

- As Found: Beta Thalassemia

- ID: M21178

- Name: Iron Overload

- Relevance: HIGH

- As Found: Iron Overload

- ID: M4070

- Name: Anemia

- Relevance: LOW

- As Found: Unknown

- ID: M9547

- Name: Hemolysis

- Relevance: LOW

- As Found: Unknown

- ID: M4073

- Name: Anemia, Hemolytic

- Relevance: LOW

- As Found: Unknown

- ID: M4075

- Name: Anemia, Hemolytic, Congenital

- Relevance: LOW

- As Found: Unknown

- ID: M9490

- Name: Hematologic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M9539

- Name: Hemoglobinopathies

- Relevance: LOW

- As Found: Unknown

- ID: M23686

- Name: Genetic Diseases, Inborn

- Relevance: LOW

- As Found: Unknown

- ID: M11639

- Name: Metabolic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M21177

- Name: Iron Metabolism Disorders

- Relevance: LOW

- As Found: Unknown

- ID: T5622

- Name: Thalassemia

- Relevance: HIGH

- As Found: Thalassemia

- ID: T737

- Name: Beta-thalassemia

- Relevance: HIGH

- As Found: Beta Thalassemia

### Condition Browse Module - Meshes

- ID: D000013789

- Term: Thalassemia

- ID: D000017086

- Term: beta-Thalassemia

- ID: D000019190

- Term: Iron Overload

### Intervention Browse Module - Browse Branches

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Micro

- Name: Micronutrients

### Intervention Browse Module - Browse Leaves

- ID: M4225

- Name: Antibodies

- Relevance: LOW

- As Found: Unknown

- ID: M10533

- Name: Iron

- Relevance: LOW

- As Found: Unknown

- ID: M10184

- Name: Immunoglobulins

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
