GNT0006 Gene Therapy Trial in Patients With LGMDR9
- Conditions
- LGMDR9
- Interventions
- Other: GNT0006
- Registration Number
- NCT05224505
- Lead Sponsor
- Atamyo Therapeutics
- Brief Summary
Phase 1-2 study including a dose escalation safety and proof of concept phase (Stage 1, open label), followed by a double-blind, randomized, placebo-controlled confirmatory phase (Stage 2)
- Detailed Description
Multicenter, Phase 1-2 study evaluating safety, pharmacodynamic, efficacy, and immunogenicity of GNT0006, an Adeno-Associated Virus (AAV) vector carrying the human FKRP transgene.
This study will consist of 2 phases: an open-label dose escalation phase (Stage 1) and a double-blind placebo controlled, randomized phase (Stage 2), both with long-term follow-up (LTFU) period.
Stage 1 Two dose cohorts will be enrolled sequentially and enrollment. An initial cohort of three (3) patients will receive a potentially effective dose, followed by a 2nd higher dose cohort of 3 patients.
Stage 2 After selection of the effective dose in Stage 1, thirty-three (33) ambulant patients will be randomized at the optimal selected dose and followed up to the primary efficacy timepoint, i.e., one year after investigational medicinal product (IMP) (or placebo) administration.
At one-year post-IMP administration (timepoint of primary interest for efficacy), patients enrolled in placebo group will receive active IMP while patients randomized in the active IMP group will receive a placebo infusion.
All subjects will be followed for up to 5 years after active IMP (GNT0006) administration.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 39
-
- Female and male ambulant patients
-
- Patients ≥ 16 years old
-
- Documented LGMDR9 diagnosis based on clinical presentation and genotyping confirming the FKRP gene mutations
-
- Moderate diaphragmatic muscle impairment
-
- Detectable serum neutralizing antibodies against AAV9
-
- Cardiomyopathy
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description GNT0006 - Stage 1 GNT0006 6 patients treated with GNT0006 in Stage 1 (open label) 2 dose cohorts : Cohort 1: single intravenous injection 9.0E+12 vg/Kg Cohort 2: single intravenous injection 2.7E+13 vg/Kg
- Primary Outcome Measures
Name Time Method Percent change from baseline in Forced Vital Capacity at one year Baseline through 12 months Primary endpoint
- Secondary Outcome Measures
Name Time Method Muscle Biopsy Baseline through 12 months Percentage of glycosylation
Patient reported outcome and quality of life assessment Baseline through 12 months ACTIVLIM, scale measuring level of limitation in performing daily activities (total score ranging from 0 to 44, with the lower score the highest limitation)
10-Meter Walk test (10MWT) Baseline through 12 months Secondary endpoint
Timed Up and Go (TUG) test Baseline through 12 months Secondary endpoint
Change from baseline in North Star Assessment for Neuromuscular Disorders (NSAD) scale (with a range from 0 to 54, the higher the score the better the ability) Baseline through 12 months Scale to assess patient's abilities necessary to remain functionally ambulant
2-minute walk distance test Baseline through 12 months Secondary endpoint
Muscle MRI Baseline through 12 months To measure change from baseline in fat repartition fraction in thigh and leg skeletal muscles
Cardiac MRI Baseline through 12 months To measure cardiac function (left ejection fraction)
Trial Locations
- Locations (3)
Institute of Myology Pitié-Salpêtrière Hospital 47 Bd de l'Hôpital
🇫🇷Paris, France
Royal Victoria Infirmary Queen Victoria Road Level 6 Leazes Wing
🇬🇧Newcastle Upon Tyne, United Kingdom
Rigshospitalet, University of Copenhagen Blegdamsvej 9
🇩🇰Copenhagen, Denmark