Studying the feasibility and safety of gene therapy to treat limb girdle muscular dystrophy (LGMD) type 2C
| ISRCTN | ISRCTN22225367 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN22225367 |
| Secondary identifying numbers | GTG001.06 |
- Submission date
- 17/03/2011
- Registration date
- 08/04/2011
- Last edited
- 08/04/2011
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Musculoskeletal Diseases
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English summary of protocol
Not provided at time of registration
Contact information
Prof Serge Herson
Scientific
Scientific
Service de Médecine Interne
Groupe Hospitalier Pitié-Salpêtrière
47 boulevard de l'Hôpital
Paris
75013
France
Study information
| Study design | Phase I open-label dose escalation three cohort single institutional clinical trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Cohort study |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | Phase I clinical study of AAV1-gamma-sarcoglycan gene therapy for limb girdle muscular dystrophy type 2C |
| Study objectives | Evaluation of clinical safety and feasibility of gene therapy in patients with limb girdle muscular dystrophy type 2C (gamma-sarcoglycanopathy) |
| Ethics approval(s) | Committee for the Protection of Persons (CPP) Ile de France VI [Comité de Protection des Personnes (CPP) Ile de France VI] approved on 10/10/2006 |
| Health condition(s) or problem(s) studied | Limb girdle muscular dystrophy (LGMD), type 2C (gamma-sarcoglycanopathy) |
| Intervention | 1. No placebo arm 2. Six month follow-up on AAV1 γ-sarcoglycan, AAV1 replication-defective vector expressing the human γ-sarcoglycan gene under the control of the desmin promoter, prepared for clinical use under cGMP conditions for biologics to be used in clinical trials 3. Three dose levels: 3x109 vg/100µl, 1,5x1010 vg/100µl and three concomitant injections of 1.5x1010 vg/100µl into the same site (i.e. a dose of 4.5x1010 vg/300µl) 4. Single intramuscular injection of product into carpi radialis muscle under open procedure 5. Enrolment of subjects on a sequential mode 6. Muscular evaluation is made periodically during the 6 following months after enrolment 7. Muscular biopsy is made on day 30 after enrolment |
| Intervention type | Other |
| Primary outcome measure | Assessment of clinical tolerance by standard clinical examination |
| Secondary outcome measures | 1. Assessment of biological, immunological, histological and functional tolerance by laboratory monitoring, evaluation of humoral and cellular immune response to both transgene and vector as well as non-specific immune response, evaluation of histological changes on muscle biopsy and evaluation of changes in muscle function 2. Assessment of efficacy through studies of transduction efficiency, distribution, expression and fiber type specificity and muscle biopsy histological changes (based on immunohistochemistry and Western blot studies and analysis of sarcoglycan labelling) |
| Overall study start date | 21/11/2006 |
| Completion date | 01/06/2010 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 9 |
| Key inclusion criteria | 1. Confirmed diagnosis of LGMD 2C including: 1.1. Molecular analysis proving del525T mutation on γ-sarcoglycan gene (chromosome 13) at homozygous state 1.2. Muscle biopsy with immunohistochemical and/or Western blot analysis showing marked decrease or absence of γ-sarcoglycan staining in muscle, as well as a fibrosis assessment should be available. If not, an initial muscular biopsy may be performed during the pre-enrolment period 2. Minimum age of 15 years 3. Males and females may be equally enrolled 4. Adequate carpi radialis muscle bulk for muscle biopsy as assessed by examination 5. Subjects should be able to communicate with the investigation staff 6. Subjects should be able to understand, to comply with and to perform all needed evaluations during the trial period including muscle strength tests 7. Forearm muscle strength should be of at least 3+ as assessed through the British Medical Research Council (MRC) Manual Muscle Testing (MMT) scale 8. Subjects should also have already lost ambulation 9. Subjects should be able and willing to return for follow up 10. Subjects should be able and willing to give signed informed consent 11. For minor subjects, a signed informed consent will be given by a legally authorised representative 12. Eligible subjects belonging to a multiplex family should not be enrolled in the same cohort |
| Key exclusion criteria | 1. Severity of disease and presence of ill-prognosis complications: 1.1. Severe respiratory dysfunction such as subjects with tracheostomy or forced vital capacity (FVC) < 1000ml and/or < 30% 1.2. Uncompensated heart failure 1.3. An ejection fraction (EF) < 30% as measured on either echocardiography or scintigraphy 1.4. Severe rhythm disturbances and/or high degree conduction defect in the absence of a pacemaker insertion 2. Underlying conditions, diseases or active viral infections likely to increase risk of complications or to interfere with the investigational treatment: 2.1. Contraindications for injections and muscle biopsies 2.2. Platelet count < 100,000/mm3 2.3. Total bilirubin > 10 mg/l (> 17 µmol/l) 2.4. Serum creatinine > 110 µmol/l 2.5. Lymphocytes CD4+ < 250/mm3 (< 15%) 2.6. History of diabetes mellitus 2.7. Current infectious diseases, including known positive human immunodeficiency virus (HIV) serology, hepatitis B and C 2.8. Abnormal profile on protein immunoelectrophoresis 2.9. Immunisations of any kind within the past month 2.10. Receipt of another investigational agent within 4 weeks of study enrolment 2.11. History of or current steroid medication for indications other than muscular dystrophy, chemotherapy, radiotherapy or other immunosuppressive therapy 2.12. Steroid medication, if any, should be discontinued at least 3 months before entering the protocol and not received during the study 2.13. Pregnant or lactating women 2.14. Females or males of childbearing age must be willing to employ adequate contraception, that is to use condoms during the 3 months following the administration of the product 2.15. Pre-injection neutralising anti-AAV1 antibodies titer (on pre-enrolment / D-30 visit) superior or equal to 1/800 |
| Date of first enrolment | 21/11/2006 |
| Date of final enrolment | 01/06/2010 |
Locations
Countries of recruitment
- France
Study participating centre
Service de Médecine Interne
Paris
75013
France
75013
France
Sponsor information
Genethon (France)
Research organisation
Research organisation
1 Bis Rue de L'Internationale
Evry
91000
France
| Website | http://www.genethon.fr |
|---|---|
"ROR" |
https://ror.org/03fj96t64 |
Funders
Funder type
Research organisation
Genethon (France)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
