EPISOD1

 

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

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 cytosolic SOD1 and thereby ameliorate the course of ALS caused by this mutant gene.

Study design

Description of study design:

• Phase I-II
• Open Label, Single Ascending Dose
• 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.
  • EXPANSION COHORT: will further test selected dose from the initial single ascending does cohort in approximately 6 to 8 participants
• Intrathecally administered
• 5 Years
• 19 Visits if study is completed over 5 Years
• Open Label
• 10 sites in the US

Can I participate in the study?

The main criteria to participate in this study are:

• 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.

Note: This list is not exhaustive, but these are the main criteria. Please visit clinicaltrials.gov using the NTC number NCT06100276 

Registration and more information

The study is only being performed at sites within the United States.  The study sites are listed on the clincialtrials.gov website.  Search for NCT06100276. This list will change, as we are in the process of activating additional sites. The ct.gov page is updated regularly.

If you are interested in participating in the EPISOD1 study and fit the above profile, please visit clinicaltrials.gov to access contact details.

For non-US residents

If you are not a US resident but you are interested in participating, please get in touch to discuss how to move forward. Inclusion in the EPISOD1 Study for non-US residents may be possible; provided, that all study inclusion criteria are met, that appropriate arrangements for insurance, travel, etc. can be made and only if a study site can be arranged in the country of residency to conduct the follow up visits.  Such inclusion would require an initial stay in the United States for approximately 6-9 months.  Approximately six months after receiving AMT-162, participants would need to return to their home country to continue the long-term safety follow up visit. Certain expenses may be able to be reimbursed for potential participants, as well as their caregivers. However, uniQure may limit the types of expenses and amounts being reimbursed and may also allow for this option at their sole discretion. Serious consideration should be given to understanding the requirements of the study before taking the next steps to participate.  Participants will be asked to be in the study for 5 years total. There are many study visits which are several hours long and require many tests to be performed.