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.
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.
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) ≥50% 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: 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.
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.