Clinical Study of AAV1-gamma-sarcoglycan Gene Therapy for Limb Girdle Muscular Dystrophy Type 2C

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT01344798
• Date of registration: 17/03/2011
• Prospective Registration: No
• Primary sponsor: Genethon
• Public title: Clinical Study of AAV1-gamma-sarcoglycan Gene Therapy for Limb Girdle Muscular Dystrophy Type 2C
• Scientific title: Phase I Clinical Study of AAV1-gamma-sarcoglycan Gene Therapy for Limb Girdle Muscular Dystrophy Type 2C
• Date of first enrolment: November 2006
• Target sample size: 9
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT01344798
• Study type: Interventional
• Study design: Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
• Phase: Phase 1

Countries of recruitment

France

Contacts

• Name: Serge Herson, Prof
• Affiliation: AP-HP

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Confirmed diagnosis of LGMD 2C including:

- Molecular analysis proving del525T mutation on ?-sarcoglycan gene (chromosome
13) at homozygous state

- Muscle biopsy with immunohistochemical and/or Western blot analyses showing
marked decrease or absence of ?-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-enrollment period

2. Lower age limit of 15 years

3. Males and females may be equally enrolled

4. Adequate carpi radialis muscle bulk for muscle biopsy as assessed by examination.
Subjects should be able to communicate with the investigation staff. They should be
able to understand, to comply with and to perform all needed evaluations during the
trial period, including muscle strength tests. Forearm muscle strength should be of
at least 3+ as assessed through the British Medical Research Council (MRC) Manual
Muscle Testing (MMT) scale.

Subjects should also have already lost ambulation

5. Subjects should be able and willing to return for follow up

6. Subjects should be able and willing to give signed informed consent. For minor
subjects, a signed informed consent will be given by legally authorized
representative

7. Eligible subjects belonging to a multiplex family should not be enrolled in the same
cohort.

Exclusion Criteria:

1. Severity of disease and presence of ill-prognosis complications:

- Severe respiratory dysfunction such as subjects with tracheostomy or forced
vital capacity (FVC) < 1000 ml and/or < 30%;

- Uncompensated heart failure;

- An ejection fraction (EF) < 30% as measured on either echocardiography or
scintigraphy;

- 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:

- contraindications for injections and muscle biopsies

- Platelet count < 100,000 / mm3

- Total bilirubin > 10 mg/l (> 17 µmol/l)

- Serum creatinin > 110 µmol/l

- Lymphocytes CD4+ < 250/mm3 (< 15%)

- History of diabetes mellitus

- Current infectious diseases, including known positive HIV serology, hepatitis B
and C

- Abnormal profile on protein immunoelectrophoresis

- Immunizations of any kind within the past month

- receipt of another investigational agent within 4 weeks of study enrollment

- History of or current steroid medication for indications other than muscular
dystrophy, chemotherapy, radiotherapy or other immunosuppressive therapy.
Steroid medication, if any, should be discontinued at least 3 months before
entering the protocol and not received during the study

- Pregnant or lactating women. 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

- Pre-injection neutralizing anti-AAV1 antibodies titer (on pre-enrollment / D-30
visit) superior or equal to 1/800.



Age minimum: 15 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Gamma-sarcoglycanopathy

Limb Girdle Muscular Dystrophy Type 2C

Intervention(s)

Biological: AAV1-gamma-sarcoglycan vector injection

Primary Outcome(s)

Number of patients with adverse events or general or local signs as a measure of clinical safety [Time Frame: 6 months]

Secondary Outcome(s)

Number of patients with changed/increased cellular immunity to AAV [Time Frame: 6 months]

Number of patients with changed/increased cellular immunity to transgene [Time Frame: 6 months]

Number of patients with changed/increased humoral immunity to transgene [Time Frame: 6 months]

Number of patients with modified biological values (blood count, standard biochemistry, viral serology) [Time Frame: 6 months]

Number of patients with modified/decreased muscular force [Time Frame: 6 months]

number of patients with changed or increased humoral immunity to AAV [Time Frame: 6 months]

number of patients with positively stained muscular fibers to gamma-sarcoglycan protein [Time Frame: 30 days]

Secondary ID(s)

GTG001.06

Source(s) of Monetary Support

Please refer to primary and secondary sponsors