Clinical trial NCT06100276: Safety, Tolerability, and Exploratory Efficacy Study of Intrathecally Administered Gene Therapy AMT-162 in Adult Participants with SOD1 Amyotrophic Lateral Sclerosis (SOD1-ALS)
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).
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Amyotrophic Lateral Sclerosis
Keywords: Gene Therapy
AAV (adeno-associated virus)
ALS
SOD1
Lead sponsor: UniQure Biopharma B.V.
Sponsor class: INDUSTRY
First posted: 2023-10-25
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: To evaluate the safety and tolerability of ascending doses of intrathecally administered AMT-162 in Participants with SOD1-ALS
timeFrame: up to 5 years
Secondary outcomes:
measure: Characterization of Immune Response to AMT-162 and Shedding of intrathecally administered AMT-162.
timeFrame: up to 5 years
measure: Characterization of the Effect of intrathecally administered AMT-162
timeFrame: up to 5 years
Other outcomes:
Locations:
city: Irvine
country: United States
facility: University of California Irvine
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine
state: Illinois
city: Fairway
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Boston
country: United States
facility: Massachusetts General Hospital, Sean M. Healey and AMG Center for ALS Research
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: Philadelphia
country: United States
facility: University of Pennsylvania School of Medicine
state: Pennsylvania
Study officials:
affiliation: UniQure Biopharma B.V.
name: Executive Director, Clinical Development
role: STUDY_DIRECTOR
References: