Clinical Intramuscular Gene Transfer of rAAV1.CMV.huFollistatin344 Trial to Patients With Duchenne Muscular Dystrophy
|ClinicalTrials.gov Identifier: NCT02354781|
Recruitment Status : Completed
First Posted : February 3, 2015
Results First Posted : April 15, 2020
Last Update Posted : April 15, 2020
|Condition or disease||Intervention/treatment||Phase|
|Duchenne Muscular Dystrophy||Biological: rAAV1.CMV.huFollistin344||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||3 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I/II Clinical Intramuscular Gene Transfer of rAAV1.CMV.huFollistatin344 Trial to Patients With Duchenne Muscular Dystrophy|
|Study Start Date :||January 2015|
|Actual Primary Completion Date :||November 2017|
|Actual Study Completion Date :||November 2017|
The vector will be delivered to both limbs via multiple, direct intramuscular injections of rAAV1.CMV.huFollistin344; the number of injections per muscle will depend on the size of the patient. A total dose of 2.4E12 vg/kg (1.2E12vg/kg/limb) will be delivered to the lower limbs of 6 DMD subjects
Six DMD patients will receive rAAV1.CMV.huFollistatin344 to both limbs by multiple injections to gluteal muscles, quadriceps and tibialis anterior muscles.
- Number of Dose Limiting Toxicity (DLT) Adverse Events as Assessed by 21 CFR 312.32. [ Time Frame: DLT Adverse events will be recorded from the date of dosing and through the time of the subject's last study visit. Serious adverse events will be recorded from the date of dosing and for up to 2 years after gene therapy administration. ]
Dose limiting toxicity (DLT) is defined as any adverse event that is possibly, probably, or definitely related to the study agent. This would include any grade 3 according to the classification given above. Study enrollment will be halted by the investigators when any subject experiences a Grade 3, or higher adverse event toxicity that is possibly, probably, or definitely related to the study drug. Only those adverse events requiring treatment will qualify as DLT.
The classification for adverse events to be used is the following:
- Mild adverse event; did not require treatment
- Moderate adverse event; resolved with treatment
- Severe adverse event; inability to carry on normal activities; required professional medical attention
- Life-threatening or permanently disabling adverse event
- Fatal adverse event In this grading system, "severe" is not equivalent to seriousness.
- Muscle Function Measured by Six-minute Walk Test (6MWT) [ Time Frame: 2 years ]Number of subjects with increased distance walked in meters on the Six Minute Walk Test The participant was asked to walk a set course of 25 meters for 6 minutes (timed) and the distance walked in meters was recorded. Increases from baseline in 6MWT distance are indicative of improvement and decreases from baseline indicate worsening.
- Expression of Viral DNA (qPCR), and Follistatin Transgene in Muscle Tissue [ Time Frame: 180.days ]
Muscle biopsies on quadriceps muscles a muscle biopsy on one leg at baseline screening visit and the post gene transfer biopsy on the opposite leg at day 180. Muscle tissue obtained at biopsy will also be assessed for viral DNA (qPCR), and follistatin transgene expression.
Measured in CMV.FS344 Gene Copy Number in Genomic DNA (Copies/ug DNA)
- Muscle Function Measured by North Star Ambulatory Assessment (NSAA) [ Time Frame: 2 years ]
Overall Improvement in North Star Ambulatory Assessment
The activities are graded as follows:
2 - "Normal" - no obvious modification of activity
1 - Modified method but achieves goal independent of physical assistance from another 0 - Unable to achieve independently This scale is ordinal with 34 as the maximum score indicating fully-independent function.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02354781
|United States, Ohio|
|Nationwide Children's Hospital|
|Columbus, Ohio, United States, 43205|
|Principal Investigator:||Jerry R Mendell, MD||Director, Center for Gene Therapy, Nationwide Children's Hospital|