NCT05243017

Safety and Efficacy of AMT-130 in European Adults With Early Manifest Huntington's Disease

A Phase Ib/II Randomized, Double-Blind Study to Explore Safety, Tolerability, and Efficacy Signals of Multiple Doses of Striatally-Administered rAAV5-miHTT Total Huntingtin Gene (HTT) Lowering Therapy (AMT 130) in Early Manifest Huntington's Disease

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 14 (actual)
• Sponsor: UniQure Biopharma B.V. · Industry
• Sex: All
• Age: 25 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

This is the second study of AMT-130 in patients with early manifest HD and is designed as part of an integrated two-study phase I/II program under a single data safety monitoring board (DSMB) with staggered enrollment based upon continued demonstration of safety of AMT-130 administration. Cohort 3 participants will receive either high or low dose (1:1 randomization). Participants enrolled in Cohort 3 will also receive an immunosuppression regimen consisting of dexamethasone, sirolimus, and rituximab.

Detailed description

The aim of the European study is to build upon the safety demonstrated in the first human dose (FHD) randomized, double blind, sham-controlled sequential dose escalation study (CT-AMT-130-01; clinicaltrials.gov NCT04120493) being conducted in the US and expand the number of patients exposed to the two doses to provide sufficient sample size for comparisons of safety and efficacy. CT-AMT-130-02 is a Phase Ib/II open-label (Cohorts 1 \& 2), randomized (Cohort 3 only) sequential multiple dose study that will be conducted in approximately 5 to 8 European HD centers; 2 of these centers will serve as surgical sites. Both studies will share a common set of clinical, safety, imaging, and biomarker evaluations over 5 years of follow-up. The DSMB will evaluate safety and other parameters to enable the staggered treatment of patients within each of the dosing cohorts Cohort 3 participants will receive either high or low dose AMT-130. Following completion of the Month 36 visit, they will be unblinded to their treatment arm. Cohort 3 will further evaluate the safety and exploratory efficacy data of low or high dose AMT-130. Cohort 3 participants will also receive pre and post-operative immunosuppressant therapies composed of dexamethasone, sirolimus, and rituximab.

Conditions

• Huntington Disease

Interventions

Type	Name	Description
GENETIC	intra-striatal rAAV5-miHTT	One time MRI-guided stereotaxic infusion of rAAV5-miHTT into the brain

Timeline

• Start date: 2021-10-07
• Primary completion: 2029-03-01
• Completion: 2029-10-07
• First posted: 2022-02-16
• Last updated: 2025-03-10

Locations

4 sites across 2 countries: Poland, United Kingdom