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

NCT05974579 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: 2024-5148
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

PET imaging; CT imaging; AP-101; 89-Zirconium; DFO

Outcome Measures

Primary Outcomes (3)

• Incidence of adverse events (AEs) and serious adverse events (SAEs)

  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)

  day 0 (post-injection) to day 14 (end of study)

• Biodistribution of [89Zr]Zr-DFO-AP-101

  Assessed by whole-body PET imaging

  Pre-dose and at 2 hours, 1, 3, 7, 10 days post-dose

• Dosimetry of [89Zr]Zr-DFO-AP-101 in human

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

  Pre-Dose and at 2 hours, 1, 3, 7, 10 days post-dose

Secondary Outcomes (4)

• Cmax

  Pre-dose and at 2 hours, 1, 3, 7, 10 days post-dose

• Area under the curve (AUC)

  Pre-dose and at 2 hours, 1, 3, 7, 10 days post-dose

• residence time

  Pre-dose and at 2 hours, 1, 3, 7, 10 days post-dose

• Excretion

  Pre-dose and at 2 hours, 1, 3, 7, 10 days post-dose

Other Outcomes (2)

• Differential labeling and uptake

  Pre-dose and at 2 hours, 1, 3, 7, 10 days post-dose

• differential uptake of neurologic components with the Ultra-High Resolution PET imaging

  Pre-dose and at 2hours, 1, 3, 7, 10 dayspost-dose

Study Arms (2)

Healthy participants

EXPERIMENTAL

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

Drug: 89Zr-DFO-AP-101

Patients with ALS

EXPERIMENTAL

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

Drug: 89Zr-DFO-AP-101

Interventions

89Zr-DFO-AP-101 DRUG

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.

Healthy participants; Patients with ALS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged of:
• For healthy participants: Male or female subjects aged 50 years or older
• For ALS patients: Male or female subjects aged 18 years and older
• Able to remain in a lying position for up to 45 minutes without respiratory support.
• 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)
• Have venous access sufficient to allow for blood sampling
• Are reliable and willing to make themselves available for the duration of the study and are willing to follow CRCHUS-specific study procedures.

You may not qualify if:

• 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.
• 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.
• Plan to have surgery or other invasive procedure during the course of the study (up to 14 days post-injection)
• 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.
• Have one of these conditions (for both patient groups):
• hepatic disorder such as hepatic encephalopathy, hepatic laboratory abnormalities (ALT or AST ≥3 × ULN or total bilirubin ≥2 × ULN) and hematology abnormalities at screening.
• severe chronic kidney disease (eg, an estimated glomerular filtration rate \[eGFR\] \<30 mL/min/1.73m or requires chronic dialysis) at screening.
• Have severe active psychiatric illness.
• Have a diagnosis of another neurodegenerative disease (e.g. Parkinson disease, Alzheimer's disease, etc).
• Have a significant infection or known inflammatory process on screening or at Day 0.
• Alcohol or drug abuse based on patient auto-report
• Have a history of relevant atopy or drug hypersensitivity or allergy to antibodies;
• 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.
• For ALS patients:
• Have undergone a tracheostomy for ALS symptoms.

Sponsors & Collaborators

• Université de Sherbrooke: lead
• Eli Lilly and Company: collaborator
• Chorus Wellness Inc.: collaborator

Study Sites (1)

CIUSSS de l'Estrie-CHUS Hospital

Sherbrooke, Quebec, J1H 5N4, Canada

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Eric E Turcotte, MD

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

  STUDY DIRECTOR

• Brigitte Guérin, PhD

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: July 11, 2023
• First Posted: August 3, 2023
• Study Start: November 23, 2023
• Primary Completion: December 30, 2024
• Study Completion: March 31, 2025
• Last Updated: January 28, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)