## Protocol Section
### Identification Module
**NCT ID:** NCT05974579

**Brief Title:** Safety and Dosimetry of a New Radiotracer to Detect Misfolded SOD1 Associated With Amyotrophic Lateral Sclerosis

**Official Title:** A Single Center, Open Label Study to Evaluate Biodistribution, Pharmacokinetics and Safety of [89Zr]Zr-DFO-AP-101 PET (Positron Emission Tomography) in Healthy Volunteers and Amyotrophic Lateral Sclerosis (ALS) Patients

#### Organization Study ID Info
**ID:** 2024-5148
#### Organization
**Class:** OTHER
**Full Name:** Université de Sherbrooke
#### Secondary ID Infos
**Domain:** CIUSSS de l'Estrie - CHUS
**ID:** 2024-5148
**Type:** OTHER
### Status Module
#### Completion Date
**Date:** 2024-07-31

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2023-11-29

**Type:** ACTUAL

**Last Update Submit Date:** 2023-11-23

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2024-05-31

**Type:** ESTIMATED

#### Start Date
**Date:** 2023-11-23

**Type:** ACTUAL

**Status Verified Date:** 2023-11

#### Study First Post Date
**Date:** 2023-08-03
**Type:** ACTUAL
**Study First Submit Date:** 2023-07-11
**Study First Submit QC Date:** 2023-07-26
### Sponsor Collaborators Module

#### Collaborators

**Class:** INDUSTRY

**Name:** Eli Lilly and Company

**Class:** INDUSTRY

**Name:** Chorus Wellness Inc.

**Class:** UNKNOWN

**Name:** AL-S Pharma AG

#### Lead Sponsor

**Class:** OTHER

**Name:** Université de Sherbrooke

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's Disease, is a rare neurodegenerative disease resulting in loss, primarily, of the motor neurons in the motor cortex, brainstem and spinal cord. It currently affects 3 of every 100,000 people in the US.

Currently, there is no diagnostic tool for ALS, resulting in misdiagnosis and significant disease progression before formal diagnosis. An imaging test for early detection of ALS and for monitoring disease progression would have significant diagnostic and prognostic value.

PET imaging with an appropriate radiotracer has great potential as a biomarker for ALS given that it would permit visualization of central nervous system (CNS) pathology in individuals living with the disease.

To that extent, the primary goal of this phase I study is evaluating the safety and biodistribution of the new tracer \[89Zr\]Zr-DFO-AP-101 in healthy volunteers and ALS patients.

**Detailed Description:** Background: Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's Disease, is a rare neurodegenerative disease resulting in loss, primarily, of the motor neurons in the motor cortex, brainstem and spinal cord. It currently affects 3 of every 100,000 people in the US. Currently, there is no diagnostic tool for ALS, resulting in misdiagnosis and significant disease progression before formal diagnosis.

Design: This is a phase I clinical trial and a 2-part, single center, open label study in healthy volunteers (Part A) and confirmed ALS patients (Part B). The primary goal is evaluating the safety and biodistribution of the radiotracer \[89Zr\]Zr-DFO-AP-101 in healthy volunteers and ALS patients via PET/CT imaging.

Objectives: The primary objectives of this study are:

(Part A) To evaluate, by PET imaging, the safety, biodistribution and dosimetry of \[89Zr\]Zr-DFO-AP-101 in healthy men and women and in ALS patients

Intervention and Follow-up: Following a screening visit, eligible participants will come to the research center for all study assessments.

* On Day 0, a single intravenous dose of \[89Zr\]Zr-DFO-AP-101 40 MBq will be administrated and a 45 min whole body PET/CT acquisition will be performed at two hours post injection. Physical exam, ECG, vital signs and blood/urine samples will be collected.
* Further PET acquisitions and same data/samples collection will be repeated at days 1, 3, 7 and 10 post-injection.
* Participants will be contacted for a final follow-up visit approximately 14 days after injection.

### Conditions Module

**Conditions:**

- Amyotrophic Lateral Sclerosis

**Keywords:**

- PET imaging

- CT imaging

- AP-101

- 89-Zirconium

- DFO

### Design Module

#### Design Info

**Allocation:** NON_RANDOMIZED

**Intervention Model:** PARALLEL

**Intervention Model Description:** Two groups will be enrolled: 8 healthy subjects and 4 patients with ALS This is non-randomized, all participants will receive the same dose of radiotracer

##### Masking Info

**Masking:** NONE

**Primary Purpose:** DIAGNOSTIC

#### Enrollment Info

**Count:** 12

**Type:** ESTIMATED

**Phases:**

- PHASE1

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Will receive 40MBq of 89Zr-DFO-AP-101, once, at Day 0.

**Intervention Names:**

- Drug: 89Zr-DFO-AP-101

**Label:** Healthy participants

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Will receive 40MBq of 89Zr-DFO-AP-101, once, at Day 0.

**Intervention Names:**

- Drug: 89Zr-DFO-AP-101

**Label:** Patients with ALS

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Healthy participants

- Patients with ALS

**Description:** At Day 0, patients will receive one dose of the radiotracer. A PET/CT scan will be done 2h post-dose.

At 1, 3, 7 and 10 days post-dose, a PET/CT scan will be repeated.

**Name:** 89Zr-DFO-AP-101

**Type:** DRUG

### Outcomes Module

#### Other Outcomes

**Description:** Assessment of target organ/tissue ratio in ALS patients versus healthy volunteers

**Measure:** Differential labeling and uptake

**Time Frame:** Pre-dose and at 2 hours, 1, 3, 7, 10 days post-dose

#### Primary Outcomes

**Description:** Number of adverse events (AEs) and serious adverse events following administration of \[89Zr\]Zr-DFO-AP-101 that are new or worsened (compared to baseline/pre-dose)

**Measure:** Incidence of adverse events (AEs) and serious adverse events (SAEs)

**Time Frame:** day 0 (post-injection) to day 14 (end of study)

**Description:** Assessed by whole-body PET imaging

**Measure:** Biodistribution of [89Zr]Zr-DFO-AP-101

**Time Frame:** Pre-dose and at 2 hours, 1, 3, 7, 10 days post-dose

**Description:** Organ activity concentration (in liver, kidneys, blood, spleen, ...) measured by drawing region of interests on the PET images.

**Measure:** Dosimetry of [89Zr]Zr-DFO-AP-101 in human

**Time Frame:** Pre-Dose and at 2 hours, 1, 3, 7, 10 days post-dose

#### Secondary Outcomes

**Description:** Maximal concentration of \[89Zr\]Zr-DFO-AP-101 in plasma over time after injection

**Measure:** Cmax

**Time Frame:** Pre-dose and at 2 hours, 1, 3, 7, 10 days post-dose

**Description:** AUC of \[89Zr\]Zr-DFO-AP-101 in plasma over time after injection

**Measure:** Area under the curve (AUC)

**Time Frame:** Pre-dose and at 2 hours, 1, 3, 7, 10 days post-dose

**Description:** Time (1/2) of residence of \[89Zr\]Zr-DFO-AP-101 in plasma

**Measure:** residence time

**Time Frame:** Pre-dose and at 2 hours, 1, 3, 7, 10 days post-dose

**Description:** Concentration of \[89Zr\]Zr-DFO-AP-101 urine over time

**Measure:** Excretion

**Time Frame:** Pre-dose and at 2 hours, 1, 3, 7, 10 days post-dose

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. Aged of:

   1. For healthy participants: Male or female subjects aged 50 years or older
   2. For ALS patients: Male or female subjects aged 18 years and older
2. Able to remain in a lying position for up to 45 minutes without respiratory support.
3. A) For ALS patients, confirmed diagnostic of definitive ALS according to El-Escorial criteria14 B) for healthy participants: no neurologic condition (confirmed by physical exam)
4. Have venous access sufficient to allow for blood sampling
5. Are reliable and willing to make themselves available for the duration of the study and are willing to follow CRCHUS-specific study procedures.

Exclusion Criteria:

1. Are currently enrolled or were enrolled in the last 12 weeks in any other clinical trial involving a study drug or off label use of a drug or device, or any other type of medical research judged not to be scientifically or medically compatible with this study.
2. Female participants who are pregnant or breast feeding; or women of childbearing potential (\<50 years old) and men who are sexually active who are not willing to use an accepted effective contraceptive method.
3. Plan to have surgery or other invasive procedure during the course of the study (up to 14 days post-injection)
4. Have a progressive medical illness including, but not limited to, any cardiovascular, hepatic, respiratory, hematological, endocrine, psychiatric or neurological disease, convulsions, or any clinically significant laboratory abnormality at screening and at first visit (D0) that, in the judgment of the medical doctor, indicate a medical problem that would preclude study participation.
5. Have one of these conditions (for both patient groups):

   1. hepatic disorder such as hepatic encephalopathy, hepatic laboratory abnormalities (ALT or AST ≥3 × ULN or total bilirubin ≥2 × ULN) and hematology abnormalities at screening.
   2. severe chronic kidney disease (eg, an estimated glomerular filtration rate \[eGFR\] \<30 mL/min/1.73m or requires chronic dialysis) at screening.
   3. Have severe active psychiatric illness.
   4. Have a diagnosis of another neurodegenerative disease (e.g. Parkinson disease, Alzheimer's disease, etc).
   5. Have a significant infection or known inflammatory process on screening or at Day 0.
   6. Alcohol or drug abuse based on patient auto-report
   7. Have a history of relevant atopy or drug hypersensitivity or allergy to antibodies;
   8. Have an abnormal blood pressure (supine) defined as a diastolic blood pressure \>90 or \<45 mmHg and/or a systolic blood pressure \>160 or \<90 mmHg. Re-testing may occur once during the screening visit within 2 hours of the initial abnormal blood pressure measurement at the discretion of the investigator.
6. For ALS patients:

   1. Have undergone a tracheostomy for ALS symptoms.
   2. Are on nasal intermittent positive pressure ventilation (NIPPV) \>4h during the day, while awake for the treatment of ALS related symptoms.
   3. Have other causes of neuromuscular weakness.
7. Have received treatment with biologic agents (such as monoclonal antibodies, including marketed drugs and AP-101) within 3 months or 5 half-lives (whichever is longer) prior to study drug injection.
8. Have received any blood or blood products within the 3 months prior to screening.
9. Cannot communicate reliably with the investigator.
10. Are unwilling or unable to give written informed consent.
11. In the opinion of the medical doctor or his/her delegate, are unsuitable for inclusion in the study.

**Healthy Volunteers:** True

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** amelie.tetu.ciussse-chus@ssss.gouv.qc.ca

**Name:** Amelie Tetu, MSc

**Phone:** 819-346-1110

**Role:** CONTACT

**Contact 2:**

**Email:** sarah.cote-bigras.ciussse-chus@ssss.gouv.qc.ca

**Name:** Sarah Côté-Bigras, MSc

**Phone:** 819-346-1110

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Sherbrooke

**Contacts:**

***Contact 1:***

- **Email:** amelie.tetu.ciussse-chus@ssss.gouv.qc.ca

- **Name:** Amelie Tetu

- **Role:** CONTACT

***Contact 2:***

- **Email:** sarah.cote-bigras.ciussse-chus@ssss.gouv.qc.ca

- **Name:** Sarah Côté-Bigras

- **Role:** CONTACT

***Contact 3:***

- **Name:** Brigitte Guérin, PhD

- **Role:** PRINCIPAL_INVESTIGATOR

***Contact 4:***

- **Name:** Eric E Turcotte, MD

- **Role:** SUB_INVESTIGATOR

**Country:** Canada

**Facility:** CIUSSS de l'Estrie-CHUS Hospital

**State:** Quebec

**Status:** RECRUITING

**Zip:** J1H 5N4

#### Overall Officials

**Official 1:**

**Affiliation:** Estrie University Integrated Health and Social Services Center - University Hospital of Sherbrooke

**Name:** Eric E Turcotte, MD

**Role:** STUDY_DIRECTOR

**Official 2:**

**Affiliation:** Estrie University Integrated Health and Social Services Center - University Hospital of Sherbrooke

**Name:** Brigitte Guérin, PhD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000010335

- Term: Pathologic Processes

- ID: D000019636

- Term: Neurodegenerative Diseases

- ID: D000009422

- Term: Nervous System Diseases

- ID: D000009468

- Term: Neuromuscular Diseases

- ID: D000013118

- Term: Spinal Cord Diseases

- ID: D000002493

- Term: Central Nervous System Diseases

- ID: D000057177

- Term: TDP-43 Proteinopathies

- ID: D000057165

- Term: Proteostasis Deficiencies

- ID: D000008659

- Term: Metabolic Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: BC18

- Name: Nutritional and Metabolic Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M15415

- Name: Sclerosis

- Relevance: HIGH

- As Found: Sclerosis

- ID: M18879

- Name: Motor Neuron Disease

- Relevance: HIGH

- As Found: Lateral Sclerosis

- ID: M4024

- Name: Amyotrophic Lateral Sclerosis

- Relevance: HIGH

- As Found: Amyotrophic Lateral Sclerosis

- ID: M21558

- Name: Neurodegenerative Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12411

- Name: Neuromuscular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M15915

- Name: Spinal Cord Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5742

- Name: Central Nervous System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M28759

- Name: TDP-43 Proteinopathies

- Relevance: LOW

- As Found: Unknown

- ID: M28747

- Name: Proteostasis Deficiencies

- Relevance: LOW

- As Found: Unknown

- ID: M11639

- Name: Metabolic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T349

- Name: Amyotrophic Lateral Sclerosis

- Relevance: HIGH

- As Found: Amyotrophic Lateral Sclerosis

- ID: T4699

- Name: Primary Lateral Sclerosis

- Relevance: HIGH

- As Found: Lateral Sclerosis

### Condition Browse Module - Meshes

- ID: D000016472

- Term: Motor Neuron Disease

- ID: D000000690

- Term: Amyotrophic Lateral Sclerosis

- ID: D000012598

- Term: Sclerosis

### Misc Info Module

- Version Holder: 2024-05-24
