Clinical trial

Phase I/II Clinical Intramuscular Gene Transfer of rAAV1.CMV.huFollistatin344 Trial to Patients With Duchenne Muscular Dystrophy

Name

14-00630

Description

The proposed clinical trial is an outgrowth of the safety record and functional improvement seen in the BMD follistatin gene therapy trial. In this study the investigators propose to inject AAV1.CMV.huFS344 at a total dose of 2.4E12 vg/kg to six DMD patients. This dose will be divided between gluteal muscles, quadriceps and tibialis anterior. This is a wider distribution of vector than given to BMD patients, who overall improved the distance walked on the 6MWT without adverse events related to viral transduction into a single muscle.

Trial arms

Trial start

2015-01-01

Estimated PCD

2017-11-01

Trial end

2017-11-01

Status

Completed

Phase

Early phase I

Treatment

rAAV1.CMV.huFollistin344

Six DMD patients will receive rAAV1.CMV.huFollistatin344 to both limbs by multiple injections to gluteal muscles, quadriceps and tibialis anterior muscles.

Arms:

Experimental

Size

Primary endpoint

Number of Dose Limiting Toxicity (DLT) Adverse Events as Assessed by 21 CFR 312.32.

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.

Eligibility criteria

Inclusion Criteria: * Age 7 or older * Confirmed DMD gene mutations * Impaired muscle function based on clinical evidence including difficulty climbing stairs, getting from the floor (Gowers' sign), and weakness of individual muscles of extremities * Males of any ethnic group will be eligible * Ability to cooperate with study procedures including muscle testing. * Willingness of sexually active subjects with reproductive capacity to practice reliable method of contraception * Subjects must be on stable dose of prednisone for three months at time of enrollment or be started on oral dose of daily prednisone regimen for 30 days prior to gene transfer. Study participants will continue prednisone post gene transfer unless there is adverse event that warrants prednisone taper or withdrawal. Exclusion Criteria: * Active viral infection based on clinical observations. * The presence of a DMD gene mutation without weakness or loss of function * Symptoms or signs of cardiomyopathy, including: * Dyspnea on exertion, pedal edema, shortness of breath upon lying flat, or rales at the base of the lungs * Echocardiogram with ejection fraction below 40% * Serological evidence of HIV infection, or Hepatitis A, B or C infection * Diagnosis of (or ongoing treatment for) an autoimmune disease * Concomitant illness or requirement for chronic drug treatment that in the opinion of the PI creates unnecessary risks for gene transfer * Subjects with rAAV1 binding antibody titers \> 1:50 as determined by ELISA immunoassay * Abnormal laboratory values for liver, kidney, CBC, in the clinically significant range, based upon normal values in the Nationwide Children's Hospital Laboratory

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1', 'PHASE2'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'OTHER', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 3, 'type': 'ACTUAL'}}

Updated at

2023-10-11

1 organization

1 product

1 indication

Organization

Jerry R. Mendell

Product

rAAV1.CMV.huFollistin344

Indication

Duchenne muscular dystrophy