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)
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.
Percent change from baseline in Forced Vital Capacity at one year [ Time Frame: Baseline through 12 months ]
Primary endpoint
10-Meter Walk test (10MWT) [ Time Frame: Baseline through 12 months ]
Secondary endpoint
Timed Up and Go (TUG) test [ Time Frame: 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) [ Time Frame: Baseline through 12 months ]
Scale to assess patient's abilities necessary to remain functionally ambulant
2-minute walk distance test [ Time Frame: Baseline through 12 months ]
Secondary endpoint
Cardiac MRI [ Time Frame: Baseline through 12 months ]
To measure cardiac function (left ejection fraction)
Muscle MRI [ Time Frame: Baseline through 12 months ]
To measure change from baseline in fat repartition fraction in thigh and leg skeletal muscles
Muscle Biopsy [ Time Frame: Baseline through 12 months ]
Quantification of FKRP positive muscle fibers
Muscle Biopsy [ Time Frame: Baseline through 12 months ]
Percentage of glycosylation
Patient reported outcome and quality of life assessment [ Time Frame: Baseline through 12 months ]
Quality of Life in genetic Neuromuscular Disease (QoL-gNMD), with a range from 0 to 78, the higher the score the worse the quality of life
Patient reported outcome and quality of life assessment [ Time Frame: 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)
Ages Eligible for Study: 16 Years to 99 Years (Child, Adult, Older Adult)
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No
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
1. Detectable serum neutralizing antibodies against AAV9
2. Cardiomyopathy
Denmark
Rigshospitalet, University of Copenhagen Blegdamsvej 9 Recruiting
Copenhagen, Denmark, 2100
Contact: John Vissing, Pr +45 35452562 john.vissing@regionh.dk
France
Institute of Myology Pitié-Salpêtrière Hospital 47 Bd de l'Hôpital Recruiting
Paris, France, 75013
Contact: Tanya Stojkovic, Dr +33 (0) 1 42 16 58 70 essais-adultes@institut-myologie.org
United Kingdom
Royal Victoria Infirmary Queen Victoria Road Level 6 Leazes Wing Not yet recruiting
Newcastle Upon Tyne, United Kingdom, NE1 4LP
Contact: Volker Straub, Pr +44 (0) 191 241 8762 volker.straub@newcastle.ac.uk
Atamyo Therapeutics
N/A
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