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

NCT06100276 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: AMT-162-001
• Study Type: interventional
• Target: 20
• Locations: 2 countries
• Sites: 12

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.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

Gene Therapy; AAV (adeno-associated virus); ALS; SOD1

Outcome Measures

Primary Outcomes (1)

• To evaluate the safety and tolerability of ascending doses of intrathecally administered AMT-162 in Participants with SOD1-ALS

  Occurrence of TEAEs upon administration of ascending doses of AMT-162

  up to 5 years

Secondary Outcomes (2)

• Characterization of Immune Response to AMT-162 and Shedding of intrathecally administered AMT-162.

  up to 5 years

• Characterization of the Effect of intrathecally administered AMT-162

  up to 5 years

Study Arms (2)

3 single Ascending Dose Levels

EXPERIMENTAL

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.

Drug: AMT-162

EXPANSION COHORT

EXPERIMENTAL

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.

Drug: AMT-162

Interventions

AMT-162 DRUG

AMT-162, the investigational product (IP), is a nonreplicating, rep/cap-deleted, self-complementary Recombinant adeno-associated virus (rAAV) vector based on adeno-associated virus (AAV) serotype rh10 and contains complementary deoxyribonucleic acid (cDNA) encoding an artificial miRNA targeting the SOD1 gene.

3 single Ascending Dose Levels; EXPANSION COHORT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• ALSFRS-R score ≥ 25 at Screening.
• Slow vital capacity (SVC) ≥50% of predicted normal value.
• 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.

You may not qualify if:

• SOD1 pathogenic or likely pathogenic variants in amino acid regions 43-47.
• Pathogenic repeat expansion in the C9orf72 gene
• Any of the following prior or concomitant treatments:
• Any prior SOD1 suppression therapy with viral microRNA mediators
• 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.
• 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.
• Any prior administration of an AAV gene therapy.
• Participants must be willing to forego new ALS treatments through at least 6 months after infusion of AMT-162. After 6 months, Investigators and participants may decide to add new ALS medications or change existing ALS medications.

Sponsors & Collaborators

• UniQure Biopharma B.V.: lead

Study Sites (12)

Barrow Neurological Institute

Phoenix, Arizona, 85013, United States

Location

University of California Irvine

Irvine, California, 92697, United States

Location

California Pacific Medical Center

San Francisco, California, 94109, United States

Location

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

University of Kansas Medical Center

Fairway, Kansas, 66205, United States

Location

Massachusetts General Hospital, Sean M. Healey and AMG Center for ALS Research

Boston, Massachusetts, 02114, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

University of Pennsylvania School of Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

Norrlands Universitetssjukhus

Umeå, Vasterbottens Ian, Sweden

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

• Executive Director, Clinical Development

  UniQure Biopharma B.V.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 20, 2023
• First Posted: October 25, 2023
• Study Start: August 1, 2024
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): June 30, 2031
• Last Updated: October 22, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1); US (11)