Limb Girdle Muscular Dystrophy Type 2CPhase 1NCT01344798
Clinical Study of AAV1-gamma-sarcoglycan Gene Therapy for Limb Girdle Muscular Dystrophy Type 2C
A Phase 1 study testing AAV1-gamma-sarcoglycan vector injection in people with Limb Girdle Muscular Dystrophy Type 2C and Gamma-sarcoglycanopathy, run by Genethon at 1 site in France.
Trial 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). Read more about this study
- Who is it for?
- Ages 15 years and older
- Conditions the study is for
- Limb Girdle Muscular Dystrophy Type 2C, Gamma-sarcoglycanopathy
- What is being tested?
- AAV1-gamma-sarcoglycan vector injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteFrance
- Study dates
- Nov 2006to Jun 2010
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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:
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I Clinical Study of AAV1-gamma-sarcoglycan Gene Therapy for Limb Girdle Muscular Dystrophy Type 2C
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).
- Being tested
- AAV1-gamma-sarcoglycan vector injection
- Keywords
- limb girdle muscular dystrophy type 2C, gamma-sarcoglycanopathy, gene therapy, AAV vector, neuromuscular disease, orphan disease
- Medical subject headings
- Limb-girdle muscular dystrophy, type 2C, Neuromuscular Diseases, Rare Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AAV1-gamma-sarcoglycan vector injectionBiological
Also called in vivo gene therapy - Intramuscular route
single intramuscular injection into carpi radialis muscle under open procedure
| Study group | Role | What they receive |
|---|---|---|
| Dose level 1 | Experimental | AAV1-gamma-sarcoglycan vector dose level: 3x10e9 vg/100µl Receives: Biological: AAV1-gamma-sarcoglycan vector injection |
| Dose level 2 | Experimental | AAV1-gamma-sarcoglycan vector dose level: 1.5x10e10 vg/100µl Receives: Biological: AAV1-gamma-sarcoglycan vector injection |
| Dose level 3 | Experimental | AAV1-gamma-sarcoglycan vector dose level: 4.5x10e10 vg/300µl Receives: Biological: AAV1-gamma-sarcoglycan vector injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months
Secondary outcomes (7)
Number of patients with modified biological values (blood count, standard biochemistry, viral serology)
Assessment of biological tolerance:
- blood count
- standard biochemistry
- CPK viral serology (hepatitis B \& C)
Measured: 6 months
number of patients with changed or increased humoral immunity to AAV
assessment of anti-AAV antibodies titers
Measured: 6 months
Number of patients with changed/increased humoral immunity to transgene
assessment of anti-gamma-sarcoglycan antibodies titers
Measured: 6 months
Number of patients with changed/increased cellular immunity to AAV
assessment cellular immunity against AAV (ELispot assay)
Measured: 6 months
Number of patients with changed/increased cellular immunity to transgene
assessment cellular immunity against gamma-sarcoglycan (ELispot assay)
Measured: 6 months
number of patients with positively stained muscular fibers to gamma-sarcoglycan protein
Muscular biopsy immunohistaining for the detection of gamma-sarcoglycan
Measured: 30 days
Number of patients with modified/decreased muscular force
functional testing of treated muscle through a specially designed ergometer
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2011 (estimated)
- Study startNov 2006
- Primary completionJun 2010
- Study completionJun 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Limb Girdle Muscular Dystrophy Type 2CStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genethon
- Sponsor type
- University, hospital or other
- Investigators
- Serge Herson, Prof, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01344798
- Sponsor's protocol ID
- GTG001.06
- Status last verified
- Apr 2011
- First submitted
- 17 Mar 2011
- Last updated
- 29 Apr 2011
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Clinical Study of AAV1-gamma-sarcoglycan Gene Therapy for Limb Girdle Muscular Dystrophy Type 2C
- ClinicalTrials.gov ID
- NCT01344798
- Acronym / sponsor ID
- GTG001.06
- Keywords
- limb girdle muscular dystrophy type 2C, gamma-sarcoglycanopathy, gene therapy, AAV vector, neuromuscular disease, orphan disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- GenethonUniversity, hospital or other
- Study start
- Nov 2006
- Primary completion
- Jun 2010 (actual)
- Study completion
- Jun 2010 (actual)
- First posted
- 29 Apr 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Dose level 1 | Experimental | Biological: AAV1-gamma-sarcoglycan vector injectionAAV1-gamma-sarcoglycan vector dose level: 3x10e9 vg/100µl |
| Dose level 2 | Experimental | Biological: AAV1-gamma-sarcoglycan vector injectionAAV1-gamma-sarcoglycan vector dose level: 1.5x10e10 vg/100µl |
| Dose level 3 | Experimental | Biological: AAV1-gamma-sarcoglycan vector injectionAAV1-gamma-sarcoglycan vector dose level: 4.5x10e10 vg/300µl |
Who may qualify
- Ages
- 15 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- Confirmed diagnosis of LGMD 2C including:
- 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
Key exclusion criteria (19 listed)
- Severity of disease and presence of ill-prognosis complications:
- Underlying conditions, diseases or active viral infections likely to increase risk of complications or to interfere with the investigational treatment:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AAV1-gamma-sarcoglycan vector injectionAlso: in vivo gene therapy - Intramuscular routesingle intramuscular injection into carpi radialis muscle under open procedure | Biological | Dose level 1, Dose level 2, Dose level 3 |
Primary outcome
Number of patients with adverse events or general or local signs as a measure of clinical safety
Time frame: 6 months
Standard general and local clinical examination as well as vital signs assessement, including pain, local inflammation, stiffness and fatigability.
7 secondary outcomes
Number of patients with modified biological values (blood count, standard biochemistry, viral serology)
Time frame: 6 months
number of patients with changed or increased humoral immunity to AAV
Time frame: 6 months
Number of patients with changed/increased humoral immunity to transgene
Time frame: 6 months
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 positively stained muscular fibers to gamma-sarcoglycan protein
Time frame: 30 days
Number of patients with modified/decreased muscular force
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2011.
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Limb-girdle Muscular Dystrophy
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Serge Herson, Prof principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AAV1-gamma-sarcoglycan vector injection in people with Limb Girdle Muscular Dystrophy Type 2C and Gamma-sarcoglycanopathy, run by Genethon at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Apr 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients with adverse events or general or local signs as a measure of clinical safety (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Apr 2011.