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

NCT ID: NCT06100276

Last Updated: 2025-10-22

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-08-01
• Study Completion Date: 2031-06-30

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.

Conditions

Amyotrophic Lateral Sclerosis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

3 single Ascending Dose Levels

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.

Group Type: EXPERIMENTAL

AMT-162

Intervention Type: 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.

EXPANSION COHORT

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.

Group Type: EXPERIMENTAL

AMT-162

Intervention Type: 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.

Interventions

AMT-162

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

UniQure Biopharma B.V.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Executive Director, Clinical Development

Role: STUDY_DIRECTOR

UniQure Biopharma B.V.

Locations

Barrow Neurological Institute

Phoenix, Arizona, United States

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

Norrlands Universitetssjukhus

Umeå, Vasterbottens Ian, Sweden

Countries

United States; Sweden

Other Identifiers

AMT-162-001

Identifier Type: -

Identifier Source: org_study_id