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

NCT01344798 | Completed Phase 1 DMC

• 1 other identifier: GTG001.06
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this trial is to study the evaluation of clinical safety and feasibility of gene therapy in patients with limb girdle muscular dystrophy type 2C (gamma-sarcoglycanopathy).

Conditions

Limb Girdle Muscular Dystrophy Type 2C; Gamma-sarcoglycanopathy

Keywords

limb girdle muscular dystrophy type 2C; gamma-sarcoglycanopathy; gene therapy; AAV vector; neuromuscular disease; orphan disease

Outcome Measures

Primary Outcomes (1)

• Number of patients with adverse events or general or local signs as a measure of clinical safety

  Standard general and local clinical examination as well as vital signs assessement, including pain, local inflammation, stiffness and fatigability.

  6 months

Secondary Outcomes (7)

• Number of patients with modified biological values (blood count, standard biochemistry, viral serology)

  6 months

• number of patients with changed or increased humoral immunity to AAV

  6 months

• Number of patients with changed/increased humoral immunity to transgene

  6 months

• Number of patients with changed/increased cellular immunity to AAV

  6 months

• Number of patients with changed/increased cellular immunity to transgene

  6 months

Study Arms (3)

Dose level 1

EXPERIMENTAL

AAV1-gamma-sarcoglycan vector dose level: 3x10e9 vg/100µl

Biological: AAV1-gamma-sarcoglycan vector injection

Dose level 2

EXPERIMENTAL

AAV1-gamma-sarcoglycan vector dose level: 1.5x10e10 vg/100µl

Biological: AAV1-gamma-sarcoglycan vector injection

Dose level 3

EXPERIMENTAL

AAV1-gamma-sarcoglycan vector dose level: 4.5x10e10 vg/300µl

Biological: AAV1-gamma-sarcoglycan vector injection

Interventions

AAV1-gamma-sarcoglycan vector injection BIOLOGICAL

single intramuscular injection into carpi radialis muscle under open procedure

Also known as: in vivo gene therapy - Intramuscular route

Dose level 1; Dose level 2; Dose level 3

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed diagnosis of LGMD 2C including:
• Molecular analysis proving del525T mutation on γ-sarcoglycan gene (chromosome 13) at homozygous state
• Muscle biopsy with immunohistochemical and/or Western blot analyses 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-enrollment period
• Lower age limit of 15 years
• Males and females may be equally enrolled
• 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
• Subjects should be able and willing to return for follow up
• 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
• Eligible subjects belonging to a multiplex family should not be enrolled in the same cohort.

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Genethon: lead

Study Sites (1)

Hôpital Pitié-Salpêtrière

Paris, 75013, France

Location

MeSH Terms

Conditions

Limb-girdle muscular dystrophy, type 2C; Neuromuscular Diseases; Rare Diseases

Condition Hierarchy (Ancestors)

Nervous System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Serge Herson, Prof

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: March 17, 2011
• First Posted: April 29, 2011
• Study Start: November 1, 2006
• Primary Completion: June 1, 2010
• Study Completion: June 1, 2010
• Last Updated: April 29, 2011

Record last verified: 2011-04

Locations

FR (1)