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

Amyotrophic Lateral Sclerosis Clinical Trial

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).

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06100276
• Other study ID #: AMT-162-001
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: May 30, 2024
• Est. completion date: March 30, 2031

Study information

• Verified date: May 2024
• Source: UniQure Biopharma B.V.
• Contact: Director, Clinical Operations
• Phone: +1 339 970 7000
• Email: amt162_clinical_trials[@]uniqure.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 12
• Est. completion date: March 30, 2031
• Est. primary completion date: September 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

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.

Locations

Country	Name	City	State
United States	Massachusetts General Hospital, Sean M. Healey and AMG Center for ALS Research	Boston	Massachusetts
United States	Northwestern University Feinberg School of Medicine	Chicago	Illinois
United States	University of California Irvine	Irvine	California
United States	Columbia University Irving Medical Center	New York	New York
United States	University of Pensylvania School of Medicine	Philadelphia	Pennsylvania
United States	California Pacific Medical Center	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
UniQure Biopharma B.V.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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