FKRP-related limb-girdle muscular dystrophy (LGMD R9) MedDRA version: 20.0 Level: PT Classification code 10028356 Term: Muscular dystrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: rAAV9-hFKRPco_miR-208a
Product Code: GNT0006
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: not yet available
Current Sponsor code: GNT0006
Other descrip
Sponsors
Atamyo Therapeutics
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Ambulant male or female patients at least 16 years old 2. Documented LGMDR9 diagnosis based on clinical presentation and genotyping confirming the FKRP gene mutations 3. Able to: • Perform the 10-meter walk test (10MWT) within 30 sec with unilateral help, such as cane, or bilateral help, such as elbow crutches or orthotic devices below the knees • Rise from a standard-height chair with or without arm support 4. Diaphragmatic muscle impairment defined as forced vital capacity (FVC) between 40 and 80% (inclusive) of the expected value 5. Effective contraception • If sexually active male patients, commitment to use barrier contraception such as condom from the day of IMP administration and up to 12 month-visit after IMP administration. In addition, the female partner of childbearing potential is encouraged to use effective contraception up to the 12-month visit after IMP administration. • If female patients of childbearing potential, commitment to use highly effective methods of contraception from signature of informed consent to participate to this trial and up to 12 month-visit after IMP administration with negative blood pregnancy test at screening visit 6. Signed written informed consent before any study related procedure is performed 7. Patient medical status sufficiently stable and ability of patient and parents/legal guardian, in the opinion of the Investigator, to adhere to the study visit schedule and other protocol requirements. Are the trial subjects under 18? yes Number of subjects for this age range: 5 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 32 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
Exclusion criteria: 1. Detectable serum neutralizing antibodies against AAV9 2. Known hypersensitivity to IMP excipients, to eculizumab, murine proteins, or any excipients in eculizumab formulation 3. Cardiomyopathy based on physical and cardiological examination and echocardiography with Left Ventricular Ejection Fraction (LVEF) below 50% 4. Any respiratory assistance, including non-invasive daytime or nocturnal ventilation 5. Inability to cooperate with muscle testing or to perform respiratory function tests 6. Presence or history of concomitant muscular or other medical condition that might interfere with LGMDR9 evolution or that would confound scientific rigor or interpretation of results, e.g., current infectious episode (pulmonary, ENT,...), abnormal laboratory test if clinically significant 7. Acute illness within 4 weeks of the anticipated IMP administration which may interfere with study assessments 8. Recent immunosuppressive treatment within 3 months prior to screening 9. Current or history of significant heart, lung, hepato-biliary or renal disease or impairment that jeopardize the safety of the subject according to the investigator 10. Current participation in a clinical trial of another investigational medicinal product 11. Previous participation in gene and cell therapy trials 12. Any condition that would contraindicate treatment with immunosuppressant therapy 13. Presence of any permanent items (e.g., metal braces) precluding undergoing MRI 14. Any vaccination 1 month prior to the planned IMP administration 15. Serology consistent with HIV exposure or active hepatitis B or C infection 16. Grade 2 or higher lab abnormalities for LFT, bilirubin, creatinine, hemoglobin, WBC count, platelet count, PT, and a PTT, according to current version of CTCAE.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Stage 1 : To assess the safety and tolerability of intravenous administration of GNT0006 in ambulant patients with LGMDR9 at two different dosage levels and to select the recommended dose for stage 2 Stage 2 : To demonstrate efficacy of intravenous administration of GNT0006 in ambulant patients with LGMDR9 one year post IMP administration;Secondary Objective: Stage 1 : To collect preliminary efficacy data Stage 2 : To assess the safety and tolerability of GNT0006 in ambulant patients with LGMDR9;Primary end point(s): The change from baseline in FVC% in sitting position (expressed as percentage of the expected value based on age, gender, weight, and height-adjusted norms) at one year post-IMP administration in the treated group as compared to the placebo group (Stage 2);Timepoint(s) of evaluation of this end point: One year post-IMP administration in Stage 2 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Muscular functional tests - Imaging assessments - Respiratory assessments - Muscular Biopsy - Patient reported outcome and quality-of-life assessment - Biomarkers ;Timepoint(s) of evaluation of this end point: 12-month | — |
Countries
Canada, Denmark, France, Germany, Norway, Sweden, United Kingdom, United States
Contacts
Public ContactSophie Olivier
Atamyo Therapeutics
Outcome results
None listed