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Trial record 21 of 386 for:    "Muscular Dystrophies"

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

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ClinicalTrials.gov Identifier: NCT02354781
Recruitment Status : Completed
First Posted : February 3, 2015
Last Update Posted : December 2, 2017
Sponsor:
Collaborators:
Duchenne Alliance
Milo Therapeutics
Information provided by (Responsible Party):
Jerry R. Mendell, Nationwide Children's Hospital

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Duchenne Muscular Dystrophy Biological: rAAV1.CMV.huFollistin344 Phase 1 Phase 2

Detailed Description:
The primary objective of this study is safety and endpoints will include hematology, serum chemistry, urinalysis, immunologic response to rAAV1 and follistatin, and reported history and observations of symptoms. Efficacy measures will be used as secondary outcomes and include the distance walked on the 6MWT, functional tests by PT, life quality questionnaire, MRI, EIM, and muscle biopsy. Subject will have follow up visits on days 7, 14, 30, 45, 60, 90, 180 and 9,12, 18 and 24 months post-gene transfer.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
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


Arm Intervention/treatment
Experimental: Experimental
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
Biological: 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.




Primary Outcome Measures :
  1. Organ system toxicity based on blood chemistries and immune studies [ Time Frame: 2 years ]
    The blood chemistries and immune studies to monitor organs system abnormalities and T cell response measured by ELISpots.


Secondary Outcome Measures :
  1. Muscle Function [ Time Frame: 2 years ]
    The distance walked on the 6MWT is the major functional outcome to be evaluated.

  2. Size of muscle fibers with lack of toxicity of follistatin following gene transfer [ Time Frame: 2 years ]
    • 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.



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Ages Eligible for Study:   7 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02354781


Locations
United States, Ohio
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
Sponsors and Collaborators
Jerry R. Mendell
Duchenne Alliance
Milo Therapeutics
Investigators
Principal Investigator: Jerry R Mendell, MD Director, Center for Gene Therapy, Nationwide Children's Hospital

Additional Information:
Publications:
Responsible Party: Jerry R. Mendell, Center Director for Gene Therapy, Nationwide Children's Hospital
ClinicalTrials.gov Identifier: NCT02354781     History of Changes
Other Study ID Numbers: 14-00630
First Posted: February 3, 2015    Key Record Dates
Last Update Posted: December 2, 2017
Last Verified: November 2017

Keywords provided by Jerry R. Mendell, Nationwide Children's Hospital:
DMD
muscular dystrophy
Follistatin

Additional relevant MeSH terms:
Muscular Dystrophies
Muscular Dystrophy, Duchenne
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked