The classic website will no longer be available as of June 25, 2024. Please use the modernized
Working… Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT06100276
Recruitment Status : Not yet recruiting
First Posted : October 25, 2023
Last Update Posted : May 23, 2024
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Amyotrophic Lateral Sclerosis Drug: AMT-162 Phase 1 Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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).
Estimated Study Start Date : May 30, 2024
Estimated Primary Completion Date : September 30, 2026
Estimated Study Completion Date : March 30, 2031

Arm Intervention/treatment
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.

Primary Outcome Measures :
  1. To evaluate the safety and tolerability of ascending doses of intrathecally administered AMT-162 in Participants with SOD1-ALS [ Time Frame: up to 5 years ]
    Occurrence of TEAEs upon administration of ascending doses of AMT-162

Secondary Outcome Measures :
  1. Characterization of Immune Response to AMT-162 and Shedding of intrathecally administered AMT-162. [ Time Frame: up to 5 years ]
    Any positive results in shedding samples will be summarized at each timepoint. Immunogenicity parameters will be summarized for each visit.

  2. Characterization of the Effect of intrathecally administered AMT-162 [ Time Frame: 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.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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) ≥65% 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: Patient 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 serious adverse events or ongoing tofersen-related adverse events
    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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT06100276

Layout table for location contacts
Contact: Director, Clinical Operations +1 339 970 7000

Layout table for location information
United States, California
University of California Irvine
Irvine, California, United States, 92697
California Pacific Medical Center
San Francisco, California, United States, 94109
Contact: Daniela Sanchez    415-600-1764   
Contact: Mackenzie Kenneally    415-600-0484   
Principal Investigator: Jonathan S Katz, MD         
Sub-Investigator: Liberty Jenkins, MD         
United States, Illinois
Northwestern University Feinberg School of Medicine
Chicago, Illinois, United States, 60611
United States, Massachusetts
Massachusetts General Hospital, Sean M. Healey and AMG Center for ALS Research
Boston, Massachusetts, United States, 02114
United States, New York
Columbia University Irving Medical Center
New York, New York, United States, 10032
United States, Pennsylvania
University of Pensylvania School of Medicine
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
UniQure Biopharma B.V.
Layout table for investigator information
Study Director: Executive Director, Clinical Development UniQure Biopharma B.V.
Layout table for additonal information
Responsible Party: UniQure Biopharma B.V. Identifier: NCT06100276    
Other Study ID Numbers: AMT-162-001
First Posted: October 25, 2023    Key Record Dates
Last Update Posted: May 23, 2024
Last Verified: May 2024

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by UniQure Biopharma B.V.:
Gene Therapy
AAV (adeno-associated virus)
Additional relevant MeSH terms:
Layout table for MeSH terms
Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Pathologic Processes
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases