Condition category
Musculoskeletal Diseases
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting
Publication status
Results overdue

Plain English Summary

Not provided at time of registration

Trial website

Contact information



Primary contact

Prof Serge Herson


Contact details

Service de Médecine Interne
Groupe Hospitalier Pitié-Salpêtrière
47 boulevard de l'Hôpital

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

Scientific title

Phase I clinical study of AAV1-gamma-sarcoglycan gene therapy for limb girdle muscular dystrophy type 2C


Study hypothesis

Evaluation of clinical safety and feasibility of gene therapy in patients with limb girdle muscular dystrophy type 2C (gamma-sarcoglycanopathy)

Ethics approval

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

Study design

Phase I open-label dose escalation three cohort single institutional clinical trial

Primary study design


Secondary study design

Cohort study

Trial setting


Trial type


Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet


Limb girdle muscular dystrophy (LGMD), type 2C (gamma-sarcoglycanopathy)


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



Phase I

Drug names

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 trial start date


Overall trial end date


Reason abandoned (if study stopped)


Participant 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

Participant type


Age group




Target number of participants


Participant 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

Recruitment start date


Recruitment end date



Countries of recruitment


Trial participating centre

Service de Médecine Interne

Sponsor information


Genethon (France)

Sponsor details

1 Bis Rue de L'Internationale

Sponsor type

Research organisation



Funder type

Research organisation

Funder name

Genethon (France)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes