Clinical trial NCT05224505: GNT0006 Gene Therapy Trial in Patients With LGMDR9
Official title: A Phase 1-2 Multicenter Study (2-stages) to Evaluate the Safety and Efficacy of Intravenous GNT0006, Adeno-associated Viral Vector Carrying the FKRP Gene, in Patients With FKRP-related Limb-girdle Muscular Dystrophy (LGMDR9, Formerly LGMD2I)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: LGMDR9
Lead sponsor: Atamyo Therapeutics
Sponsor class: INDUSTRY
First posted: 2022-02-04
Enrollment: 39
Sex: ALL
Minimum age (years): 16
Maximum age (years): 99
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Stage 1: single administration of GNT0006, open label Stage 2: randomized, placebo-controlled, double blind. One cohort will receive single administration of GNT0006 followed by a single administration of placebo one year after. The second cohort will receive single administration of placebo followed by a single administration of GNT0006 one year after
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 1. Female and male ambulant patients
* 2. Patients ≥ 16 years old
* 3. Documented LGMDR9 diagnosis based on clinical presentation and genotyping confirming the FKRP gene mutations
* 4. Moderate diaphragmatic muscle impairment

Exclusion Criteria:

* 1. Detectable serum neutralizing antibodies against AAV9
* 2. Cardiomyopathy

Primary outcomes:
measure: Percent change from baseline in Forced Vital Capacity at one year
timeFrame: Baseline through 12 months
Secondary outcomes:
measure: 10-Meter Walk test (10MWT)
timeFrame: Baseline through 12 months
measure: Timed Up and Go (TUG) test
timeFrame: Baseline through 12 months
measure: 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)
timeFrame: Baseline through 12 months
measure: 2-minute walk distance test
timeFrame: Baseline through 12 months
measure: Cardiac MRI
timeFrame: Baseline through 12 months
measure: Muscle MRI
timeFrame: Baseline through 12 months
measure: Muscle Biopsy
timeFrame: Baseline through 12 months
measure: Muscle Biopsy
timeFrame: Baseline through 12 months
measure: Patient reported outcome and quality of life assessment
timeFrame: Baseline through 12 months
measure: Patient reported outcome and quality of life assessment
timeFrame: Baseline through 12 months
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Rigshospitalet, University of Copenhagen Blegdamsvej 9
city: Paris
country: France
facility: Institute of Myology Pitié-Salpêtrière Hospital 47 Bd de l'Hôpital
city: Newcastle Upon Tyne
country: United Kingdom
facility: Royal Victoria Infirmary Queen Victoria Road Level 6 Leazes Wing
Study officials:
References: