Safety, Tolerability, and Exploratory Efficacy Study of Intrathecally Administered Gene Therapy AMT-162 in Adult Participants With SOD1 Amyotrophic Lateral Sclerosis (SOD1-ALS)

Phase 1

Recruiting

• Conditions: Amyotrophic Lateral Sclerosis
• Interventions: Drug: AMT-162

• Registration Number: NCT06100276
• Lead Sponsor: UniQure Biopharma B.V.

Brief Summary

This is the study of AMT-162 in Participants with SOD1-ALS and is designed to evaluate the safety, tolerability, and exploratory efficacy of intrathecally administered gene therapy AMT-162. AMT-162-001 is a Phase 1/2, multi-center, single ascending dose study.

Detailed Description

AMT-162 is an investigational gene therapy that encodes an artificial microribonucleic acid (microRNA or miRNA) targeting the SOD1 gene. This clinical study will test the safety of AMT-162 and explore the hypothesis that it will silence expression of mutant cytosolic SOD1 and thereby ameliorate the course of ALS caused by this mutant gene.

Study Timeline

• Study First Submitted: 2023-10-20
• Study First Submitted QC: 2023-10-20
• Study First Posted: 2023-10-25
• Study Start: 2024-08-01
• Status Verified: 2024-09
• Last Update Submitted: 2024-10-08
• Last Update Posted: 2024-10-11
• Primary Completion: 2026-09-30
• Study Completion: 2031-03-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1. Confirmed clinical and genetic diagnosis of SOD1-mediated ALS (SOD1-ALS) experiencing signs and/or symptoms of lower motor neuron dysfunction (weakness, atrophy, cramps, fasciculations), with or without upper motor neuron symptoms (weakness, bring reflexes, spasticity).
2. ALSFRS-R score ≥ 25 at Screening.
3. Slow vital capacity (SVC) ≥50% of predicted normal value.
4. Capable of providing informed consent and complying with trial procedures, including: medically able to undergo lumbar puncture and has a responsible caregiver able to attend all clinic visit with the Participant.

Exclusion Criteria

1. SOD1 pathogenic or likely pathogenic variants in amino acid regions 43-47.

2. Pathogenic repeat expansion in the C9orf72 gene

3. Any of the following prior or concomitant treatments:

   1. Any prior SOD1 suppression therapy with viral microRNA mediators
   2. Prior SOD suppression therapy with antisense oligonucleotide (ASO) mediators such as tofersen (QALSODY™). Exception: Patients who previously received tofersen may be enrolled if the last dose of tofersen was received at least 20 weeks prior to the first Screening assessment and if there were no previous tofersen-related SAEs or ongoing tofersen-related adverse events that would increase the risk of receiving AMT-162, per Investigator judgment.
   3. Other ALS medications riluzole (RILUTEK®, TIGLUTIK®), edaravone (RADICAVA®), and sodium phenylbutyrate and taururosdiol combination (RELYVRIO) or bioequivalents are allowed if dose is stable for 30 days prior to immunosuppression.
   4. Any prior administration of an AAV gene therapy.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
EXPANSION COHORT	AMT-162	Expansion cohort: To further test selected dose from the SAD part in approximately 6 to 8 participants The study will be open-label. Each Participant will receive a single dose of AMT-162 delivered via an intrathecal (IT) infusion and will be followed for up to 5 years after AMT-162 administration.
3 single Ascending Dose Levels	AMT-162	Experimental: 3 single Ascending Dose Levels The study will be open-label with an initial plan to explore 3 dose levels of AMT-162 in approximately 6 to 12 Participants in total. Each Participant will receive a single dose of AMT-162 delivered via an intrathecal (IT) infusion and will be followed for up to 5 years after AMT-162 administration.

Primary Outcome Measures

Name	Time	Method
To evaluate the safety and tolerability of ascending doses of intrathecally administered AMT-162 in Participants with SOD1-ALS	up to 5 years	Occurrence of TEAEs upon administration of ascending doses of AMT-162

Secondary Outcome Measures

Name	Time	Method
Characterization of the Effect of intrathecally administered AMT-162	up to 5 years	Change from Baseline in Slow Vital Capacity (SVC) percent of predict value, Hand-held dynamometry (HHD) scores, and Neurofilament light chain (NfL) protein levels in serum.; Immunogenicity parameters will be summarized for each visit.
Characterization of Immune Response to AMT-162 and Shedding of intrathecally administered AMT-162.	up to 5 years	Any positive results in shedding samples will be summarized at each timepoint. Immunogenicity parameters will be summarized for each visit.

Trial Locations

Locations (10)

University of California Irvine; 🇺🇸 Irvine, California, United States

California Pacific Medical Center; 🇺🇸 San Francisco, California, United States

Mayo Clinic Florida; 🇺🇸 Jacksonville, Florida, United States

Winship Cancer Institute of Emory University; 🇺🇸 Atlanta, Georgia, United States

Northwestern University Feinberg School of Medicine; 🇺🇸 Chicago, Illinois, United States

University of Kansas Medical Center; 🇺🇸 Fairway, Kansas, United States

Massachusetts General Hospital, Sean M. Healey and AMG Center for ALS Research; 🇺🇸 Boston, Massachusetts, United States

Mayo Clinic Rochester; 🇺🇸 Rochester, Minnesota, United States

Columbia University Irving Medical Center; 🇺🇸 New York, New York, United States

University of Pennsylvania School of Medicine; 🇺🇸 Philadelphia, Pennsylvania, United States