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

A Phase 1/2, Multicenter, Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Exploratory Efficacy of Intrathecally Administered Gene Therapy AMT-162 in Adult Participants With SOD1 Amyotrophic Lateral Sclerosis (SOD1-ALS).

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: AMT-162

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 Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Sweden
  • Vasterbottens Ian
    • Umeå, Vasterbottens Ian, Sweden
      • Norrlands universitetssjukhus
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Barrow Neurological Institute
  • California
    • Irvine, California, United States, 92697
      • University of California Irvine
    • San Francisco, California, United States, 94109
      • California Pacific Medical Center
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Florida
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute of Emory University
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University Feinberg School of Medicine
  • Kansas
    • Fairway, Kansas, United States, 66205
      • University of Kansas Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital, Sean M. Healey and AMG Center for ALS Research
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester
  • New York
    • New York, New York, United States, 10032
      • Columbia University Irving Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: 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.
Experimental: 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.	Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterization of Immune Response to AMT-162 and Shedding of intrathecally administered AMT-162.	Any positive results in shedding samples will be summarized at each timepoint. Immunogenicity parameters will be summarized for each visit.	up to 5 years
Characterization of the Effect of intrathecally administered AMT-162	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.	up to 5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of AMT-162	Change from Baseline in Cerebrospinal fluid (CSF) SOD1 Levels, Change from Baseline from other CSF and blood biomarkers, Change from Baselines in Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) score and at 6, 9, 12 months and up to 5 years. The ALSAQ-40 is disease specific patient reported outcome. It contains 40 questions for subjects to answer about their perceived well-being with 5 discrete scales: Physical mobility (10 items), Activities of daily living and independence (10 items), Eating and drinking (3 items), Communication (7 items) and Emotional reactions (10 items).Subjects are asked to think about the difficulties they may have experienced during the last 2 weeks and to indicate the frequency of each event by selecting one of 5 options: never/rarely/sometimes/often/always or cannot do at all.	5 years

Collaborators and Investigators

• Sponsor: UniQure Biopharma B.V.
• Investigators: Study Director: Executive Director, Clinical Development, UniQure Biopharma B.V.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2024
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): June 30, 2031

Study Registration Dates

• First Submitted: October 20, 2023
• First Submitted That Met QC Criteria: October 20, 2023
• First Posted (Actual): October 25, 2023

Study Record Updates

• Last Update Posted (Estimated): October 22, 2025
• Last Update Submitted That Met QC Criteria: October 20, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: ALS; Gene Therapy; AAV (adeno-associated virus); SOD1
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Metabolic Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Motor Neuron Disease; Nutritional and Metabolic Diseases; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: AMT-162-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No