{
  "FullStudy":{
    "Rank":217595,
    "Study":{
      "ProtocolSection":{
        "IdentificationModule":{
          "NCTId":"NCT01519349",
          "OrgStudyIdInfo":{
            "OrgStudyId":"NCH-696110"
          },
          "Organization":{
            "OrgFullName":"Nationwide Children's Hospital",
            "OrgClass":"OTHER"
          },
          "BriefTitle":"Follistatin Gene Transfer to Patients With Becker Muscular Dystrophy and Sporadic Inclusion Body Myositis",
          "OfficialTitle":"Phase I Clinical Intramuscular Gene Transfer of rAAV1.CMV.huFollistatin344 Trial to Patients With Becker Muscular Dystrophy and Sporadic Inclusion Body Myositis."
        },
        "StatusModule":{
          "StatusVerifiedDate":"November 2017",
          "OverallStatus":"Completed",
          "ExpandedAccessInfo":{
            "HasExpandedAccess":"No"
          },
          "StartDateStruct":{
            "StartDate":"January 2012"
          },
          "PrimaryCompletionDateStruct":{
            "PrimaryCompletionDate":"October 2017",
            "PrimaryCompletionDateType":"Actual"
          },
          "CompletionDateStruct":{
            "CompletionDate":"October 2017",
            "CompletionDateType":"Actual"
          },
          "StudyFirstSubmitDate":"January 23, 2012",
          "StudyFirstSubmitQCDate":"January 25, 2012",
          "StudyFirstPostDateStruct":{
            "StudyFirstPostDate":"January 26, 2012",
            "StudyFirstPostDateType":"Estimate"
          },
          "LastUpdateSubmitDate":"November 21, 2017",
          "LastUpdatePostDateStruct":{
            "LastUpdatePostDate":"November 24, 2017",
            "LastUpdatePostDateType":"Actual"
          }
        },
        "SponsorCollaboratorsModule":{
          "ResponsibleParty":{
            "ResponsiblePartyType":"Principal Investigator",
            "ResponsiblePartyInvestigatorFullName":"Jerry R. Mendell",
            "ResponsiblePartyInvestigatorTitle":"Director Center for Gene Therapy",
            "ResponsiblePartyInvestigatorAffiliation":"Nationwide Children's Hospital"
          },
          "LeadSponsor":{
            "LeadSponsorName":"Nationwide Children's Hospital",
            "LeadSponsorClass":"OTHER"
          },
          "CollaboratorList":{
            "Collaborator":[
              {
                "CollaboratorName":"Parent Project Muscular Dystrophy",
                "CollaboratorClass":"OTHER"
              },{
                "CollaboratorName":"The Myositis Association (Grant Sponsor)",
                "CollaboratorClass":"UNKNOWN"
              }
            ]
          }
        },
        "OversightModule":{
          "OversightHasDMC":"Yes"
        },
        "DescriptionModule":{
          "BriefSummary":"The investigators are performing a gene therapy clinical trial in Becker muscular dystrophy (BMD) and sporadic inclusion body myositis (sIBM) patients. Both of these conditions have an important common feature: loss of ability to walk because of weakness of the thigh muscles. The investigators plan to do a gene therapy trial to deliver a gene to muscle called follistatin (FS344) that can build muscle size and strength. If successful, the investigators can increase the size of the thigh muscle and potentially prolong a patient's ability to walk. The gene will be carried into the muscle by a virus called adeno-associated virus (AAV). This virus occurs naturally in muscle and does not cause any human disease, setting the stage for its safe use in a clinical trial.\n\nPresently there is no treatment that can reverse Becker muscular dystrophy or sporadic inclusion body myositis. Only supportive care is currently possible.\n\nIn this study, subjects with either of these diseases will have shots of the follistatin gene injected directly into thigh muscle on one (first cohort) or both legs (2nd and 3rd cohort). One hundred and eighty days following the gene delivery, the muscle will undergo biopsy to look closely at the muscle to see if the muscle fibers are bigger. Between the time of the gene transfer and the muscle biopsy, patients will be carefully monitored for any side effects of the treatment. This will include an MRI of the thigh muscle before treatment and at day 180 following treatment. Blood and urine tests, as well as physical examination will be done on the subjects during the screening visit and on days 0, 1, 2, 7, 14, 30, 60, 90, and 180 to make sure that there are no side effects from the gene injections. Sutures will be removed 2 weeks post-biopsy.\n\nAdditional blood samples will be collected at 9, 12, 18, and 24 months. Patients will be seen at the end of 1st and 2nd years for a physical exam, assessment of muscle strength and appropriate blood tests."
        },
        "ConditionsModule":{
          "ConditionList":{
            "Condition":[
              "Becker Muscular Dystrophy",
              "Sporadic Inclusion Body Myositis"
            ]
          },
          "KeywordList":{
            "Keyword":[
              "Becker muscular dystrophy",
              "BMD",
              "muscular dystrophy",
              "inclusion body myositis",
              "IBM",
              "Follistatin"
            ]
          }
        },
        "DesignModule":{
          "StudyType":"Interventional",
          "PhaseList":{
            "Phase":[
              "Phase 1"
            ]
          },
          "DesignInfo":{
            "DesignAllocation":"Non-Randomized",
            "DesignInterventionModel":"Single Group Assignment",
            "DesignPrimaryPurpose":"Other",
            "DesignMaskingInfo":{
              "DesignMasking":"None (Open Label)"
            }
          },
          "EnrollmentInfo":{
            "EnrollmentCount":"15",
            "EnrollmentType":"Actual"
          }
        },
        "ArmsInterventionsModule":{
          "ArmGroupList":{
            "ArmGroup":[
              {
                "ArmGroupLabel":"Cohort 1",
                "ArmGroupType":"Experimental",
                "ArmGroupDescription":"Low Dose: 2E11 vg/kg of rAAV1.CMV.huFollistatin344 administered via intramuscular injection unilaterally to single quadriceps muscle (n=3, sIBM only)",
                "ArmGroupInterventionList":{
                  "ArmGroupInterventionName":[
                    "Biological: rAAV1.CMV.huFollistatin344"
                  ]
                }
              },{
                "ArmGroupLabel":"Cohort 2",
                "ArmGroupType":"Experimental",
                "ArmGroupDescription":"Mid Dose: 3E11 vg/kg per quadriceps of rAAV1.CMV.huFollistatin344 administered via intramuscular injection bilaterally to both quadriceps muscles (n=6; 3 sIBM and 3 BMD)",
                "ArmGroupInterventionList":{
                  "ArmGroupInterventionName":[
                    "Biological: rAAV1.CMV.huFollistatin344"
                  ]
                }
              },{
                "ArmGroupLabel":"Cohort 3",
                "ArmGroupType":"Experimental",
                "ArmGroupDescription":"Low Dose: 6E11 vg/kg per quadriceps of rAAV1.CMV.huFollistatin344 administered via intramuscular injection bilaterally to both quadriceps muscles (n=6; 3 sIBM and 3 BMD)",
                "ArmGroupInterventionList":{
                  "ArmGroupInterventionName":[
                    "Biological: rAAV1.CMV.huFollistatin344"
                  ]
                }
              }
            ]
          },
          "InterventionList":{
            "Intervention":[
              {
                "InterventionType":"Biological",
                "InterventionName":"rAAV1.CMV.huFollistatin344",
                "InterventionDescription":"First cohort - Low Dose: 2E11 vg/kg with single leg injection (n=3 sIBM)\nSecond cohort: 3E11 vg/kg per quad (n=3 sIBM; 3 BMD)\nThird cohort: 6E11 vg/kg per quad (n=3 sIBM; 3 BMD)",
                "InterventionArmGroupLabelList":{
                  "InterventionArmGroupLabel":[
                    "Cohort 1",
                    "Cohort 2",
                    "Cohort 3"
                  ]
                }
              }
            ]
          }
        },
        "OutcomesModule":{
          "PrimaryOutcomeList":{
            "PrimaryOutcome":[
              {
                "PrimaryOutcomeMeasure":"Safety",
                "PrimaryOutcomeDescription":"Safety trial based on development of unacceptable toxicity defined as the occurrence of any Grade III or higher treatment-related toxicities.",
                "PrimaryOutcomeTimeFrame":"2 years"
              }
            ]
          },
          "SecondaryOutcomeList":{
            "SecondaryOutcome":[
              {
                "SecondaryOutcomeMeasure":"Muscle Function and Strength Testing",
                "SecondaryOutcomeDescription":"Muscle function and strength:\nMRI of quadriceps muscles (bilateral)\nMuscle biopsies on quadriceps muscles (a muscle biopsy on one leg at baseline screening visit - except for cohort 1 - and the post gene transfer biopsy on the opposite leg at day 180)\nThigh circumference measurement at baseline and post-gene transfer follow up visits up to day 180 (prior to second biopsy)",
                "SecondaryOutcomeTimeFrame":"2 years"
              }
            ]
          }
        },
        "EligibilityModule":{
          "EligibilityCriteria":"Inclusion Criteria:\n\nAll subjects [sIBM and BMD must be ambulatory and have identifiable atrophy of the quadriceps muscle with muscle weakness ≥2 standard deviations below predicted using quantitative muscle testing (maximum voluntary isometric strength testing), and difficulty getting out of chairs, climbing stairs, and getting up from the floor.\nsIBM patients include males and post-menopause females of any ethnic or racial group. Diagnosis of sIBM is based on previously published criteria that include distribution of weakness (knee extensor weakness, finger flexor weakness) and histological presence of inflammation and vacuolar myopathy. Patients with inflammation, vacuolar changes and intracellular amyloid deposits or 15/18nm filaments fulfill criteria irrespective of clinical features.\nBMD patients include adult males (>18yo) of any ethnic or racial group with proven mutation of dystrophin gene and continued ambulation after age 15 years old.\nAbility to cooperate for muscle testing\nDeficit in muscle strength greater than 2 standard deviation below age expectations\nWillingness of sexually active subjects with reproductive capacity (only male population) to practice reliable method of contraception until two negative sperm samples are obtained post gene transfer\n\nExclusion Criteria:\n\nActive viral infection\nHistory or evidence of active infection with hepatitis C, hepatitis A or B, or HIV\nPatients with any other cause of muscle weakness based on medical history and screening physical exam including: myopathy (other dystrophies, polymyositis, and dermatomyositis), neuropathy (from any cause), myasthenia gravis, and weakness related to degenerative joint disease of the spine.\nOngoing immunosuppressive therapy or immunosuppressive therapy within 3 months of starting the trial (e.g. corticosteroids, cyclosporine, tacrolimus, methotrexate, cyclophosphamide, intravenous immunoglobulin, rituximab)\nConcomitant illness or requirement for chronic drug treatment that in the opinion of the PI creates unnecessary risks for gene transfer. Patients taking any of the following drugs will be excluded: drugs for treatment of myopathy or neuropathy or agents used to treat diabetes mellitus\nKnee or ankle contractures preventing proper muscle strength testing\nPatients with AAV1 neutralizing antibody titers ≥ 1:1600 as determined by ELISA immunoassay\nPatients with history of angina and patients with past history of myocardial infarction in the past 6 months",
          "HealthyVolunteers":"No",
          "Gender":"All",
          "MinimumAge":"18 Years",
          "StdAgeList":{
            "StdAge":[
              "Adult",
              "Older Adult"
            ]
          }
        },
        "ContactsLocationsModule":{
          "OverallOfficialList":{
            "OverallOfficial":[
              {
                "OverallOfficialName":"Jerry R Mendell, M.D.",
                "OverallOfficialAffiliation":"Nationwide Children's Hospital",
                "OverallOfficialRole":"Principal Investigator"
              }
            ]
          },
          "LocationList":{
            "Location":[
              {
                "LocationFacility":"Nationwide Children's Hospital",
                "LocationCity":"Columbus",
                "LocationState":"Ohio",
                "LocationZip":"43205",
                "LocationCountry":"United States"
              }
            ]
          }
        },
        "ReferencesModule":{
          "ReferenceList":{
            "Reference":[
              {
                "ReferencePMID":"20368179",
                "ReferenceType":"background",
                "ReferenceCitation":"Kota J, Handy CR, Haidet AM, Montgomery CL, Eagle A, Rodino-Klapac LR, Tucker D, Shilling CJ, Therlfall WR, Walker CM, Weisbrode SE, Janssen PM, Clark KR, Sahenk Z, Mendell JR, Kaspar BK. Follistatin gene delivery enhances muscle growth and strength in nonhuman primates. Sci Transl Med. 2009 Nov 11;1(6):6ra15. doi: 10.1126/scitranslmed.3000112."
              },{
                "ReferencePMID":"19208403",
                "ReferenceType":"background",
                "ReferenceCitation":"Rodino-Klapac LR, Haidet AM, Kota J, Handy C, Kaspar BK, Mendell JR. Inhibition of myostatin with emphasis on follistatin as a therapy for muscle disease. Muscle Nerve. 2009 Mar;39(3):283-96. doi: 10.1002/mus.21244. Review."
              },{
                "ReferencePMID":"17164329",
                "ReferenceType":"background",
                "ReferenceCitation":"Miller TM, Kim SH, Yamanaka K, Hester M, Umapathi P, Arnson H, Rizo L, Mendell JR, Gage FH, Cleveland DW, Kaspar BK. Gene transfer demonstrates that muscle is not a primary target for non-cell-autonomous toxicity in familial amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A. 2006 Dec 19;103(51):19546-51. Epub 2006 Dec 12."
              },{
                "ReferencePMID":"25322757",
                "ReferenceType":"result",
                "ReferenceCitation":"Mendell JR, Sahenk Z, Malik V, Gomez AM, Flanigan KM, Lowes LP, Alfano LN, Berry K, Meadows E, Lewis S, Braun L, Shontz K, Rouhana M, Clark KR, Rosales XQ, Al-Zaidy S, Govoni A, Rodino-Klapac LR, Hogan MJ, Kaspar BK. A phase 1/2a follistatin gene therapy trial for becker muscular dystrophy. Mol Ther. 2015 Jan;23(1):192-201. doi: 10.1038/mt.2014.200. Epub 2014 Oct 17."
              }
            ]
          },
          "SeeAlsoLinkList":{
            "SeeAlsoLink":[
              {
                "SeeAlsoLinkLabel":"Click here for Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital",
                "SeeAlsoLinkURL":"http://www.nationwidechildrens.org/center-for-gene-therapy"
              },{
                "SeeAlsoLinkLabel":"Click here for Parent Project Muscular Dystrophy",
                "SeeAlsoLinkURL":"http://www.parentprojectmd.org"
              },{
                "SeeAlsoLinkLabel":"Click here for The Myositis Association",
                "SeeAlsoLinkURL":"http://www.myositis.org/"
              }
            ]
          }
        }
      },
      "DerivedSection":{
        "MiscInfoModule":{
          "VersionHolder":"April 22, 2020"
        },
        "ConditionBrowseModule":{
          "ConditionMeshList":{
            "ConditionMesh":[
              {
                "ConditionMeshId":"D000009136",
                "ConditionMeshTerm":"Muscular Dystrophies"
              },{
                "ConditionMeshId":"D000009220",
                "ConditionMeshTerm":"Myositis"
              },{
                "ConditionMeshId":"D000020388",
                "ConditionMeshTerm":"Muscular Dystrophy, Duchenne"
              },{
                "ConditionMeshId":"D000018979",
                "ConditionMeshTerm":"Myositis, Inclusion Body"
              }
            ]
          },
          "ConditionAncestorList":{
            "ConditionAncestor":[
              {
                "ConditionAncestorId":"D000020966",
                "ConditionAncestorTerm":"Muscular Disorders, Atrophic"
              },{
                "ConditionAncestorId":"D000009135",
                "ConditionAncestorTerm":"Muscular Diseases"
              },{
                "ConditionAncestorId":"D000009140",
                "ConditionAncestorTerm":"Musculoskeletal Diseases"
              },{
                "ConditionAncestorId":"D000009468",
                "ConditionAncestorTerm":"Neuromuscular Diseases"
              },{
                "ConditionAncestorId":"D000009422",
                "ConditionAncestorTerm":"Nervous System Diseases"
              },{
                "ConditionAncestorId":"D000030342",
                "ConditionAncestorTerm":"Genetic Diseases, Inborn"
              },{
                "ConditionAncestorId":"D000040181",
                "ConditionAncestorTerm":"Genetic Diseases, X-Linked"
              }
            ]
          },
          "ConditionBrowseLeafList":{
            "ConditionBrowseLeaf":[
              {
                "ConditionBrowseLeafId":"M10676",
                "ConditionBrowseLeafName":"Muscular Dystrophies",
                "ConditionBrowseLeafAsFound":"Muscular Dystrophy",
                "ConditionBrowseLeafRelevance":"high"
              },{
                "ConditionBrowseLeafId":"M20769",
                "ConditionBrowseLeafName":"Muscular Dystrophy, Duchenne",
                "ConditionBrowseLeafAsFound":"Becker Muscular Dystrophy",
                "ConditionBrowseLeafRelevance":"high"
              },{
                "ConditionBrowseLeafId":"M10755",
                "ConditionBrowseLeafName":"Myositis",
                "ConditionBrowseLeafAsFound":"Myositis",
                "ConditionBrowseLeafRelevance":"high"
              },{
                "ConditionBrowseLeafId":"M19595",
                "ConditionBrowseLeafName":"Myositis, Inclusion Body",
                "ConditionBrowseLeafAsFound":"Sporadic Inclusion Body Myositis",
                "ConditionBrowseLeafRelevance":"high"
              },{
                "ConditionBrowseLeafId":"M3170",
                "ConditionBrowseLeafName":"Atrophy",
                "ConditionBrowseLeafRelevance":"low"
              },{
                "ConditionBrowseLeafId":"M10675",
                "ConditionBrowseLeafName":"Muscular Diseases",
                "ConditionBrowseLeafRelevance":"low"
              },{
                "ConditionBrowseLeafId":"M21281",
                "ConditionBrowseLeafName":"Muscular Disorders, Atrophic",
                "ConditionBrowseLeafRelevance":"low"
              },{
                "ConditionBrowseLeafId":"M10680",
                "ConditionBrowseLeafName":"Musculoskeletal Diseases",
                "ConditionBrowseLeafRelevance":"low"
              },{
                "ConditionBrowseLeafId":"M10994",
                "ConditionBrowseLeafName":"Neuromuscular Diseases",
                "ConditionBrowseLeafRelevance":"low"
              },{
                "ConditionBrowseLeafId":"M22270",
                "ConditionBrowseLeafName":"Genetic Diseases, Inborn",
                "ConditionBrowseLeafRelevance":"low"
              },{
                "ConditionBrowseLeafId":"M23464",
                "ConditionBrowseLeafName":"Genetic Diseases, X-Linked",
                "ConditionBrowseLeafRelevance":"low"
              },{
                "ConditionBrowseLeafId":"T3988",
                "ConditionBrowseLeafName":"Muscular Dystrophy",
                "ConditionBrowseLeafAsFound":"Muscular Dystrophy",
                "ConditionBrowseLeafRelevance":"high"
              },{
                "ConditionBrowseLeafId":"T700",
                "ConditionBrowseLeafName":"Becker Muscular Dystrophy",
                "ConditionBrowseLeafAsFound":"Becker Muscular Dystrophy",
                "ConditionBrowseLeafRelevance":"high"
              },{
                "ConditionBrowseLeafId":"T1956",
                "ConditionBrowseLeafName":"Duchenne Muscular Dystrophy",
                "ConditionBrowseLeafAsFound":"Becker Muscular Dystrophy",
                "ConditionBrowseLeafRelevance":"high"
              },{
                "ConditionBrowseLeafId":"T3012",
                "ConditionBrowseLeafName":"Idiopathic Inflammatory Myopathy",
                "ConditionBrowseLeafAsFound":"Myositis",
                "ConditionBrowseLeafRelevance":"high"
              },{
                "ConditionBrowseLeafId":"T3051",
                "ConditionBrowseLeafName":"Inclusion Body Myositis",
                "ConditionBrowseLeafAsFound":"Inclusion Body Myositis",
                "ConditionBrowseLeafRelevance":"high"
              }
            ]
          },
          "ConditionBrowseBranchList":{
            "ConditionBrowseBranch":[
              {
                "ConditionBrowseBranchAbbrev":"BC05",
                "ConditionBrowseBranchName":"Muscle, Bone, and Cartilage Diseases"
              },{
                "ConditionBrowseBranchAbbrev":"BC10",
                "ConditionBrowseBranchName":"Nervous System Diseases"
              },{
                "ConditionBrowseBranchAbbrev":"BC16",
                "ConditionBrowseBranchName":"Diseases and Abnormalities at or Before Birth"
              },{
                "ConditionBrowseBranchAbbrev":"All",
                "ConditionBrowseBranchName":"All Conditions"
              },{
                "ConditionBrowseBranchAbbrev":"BC23",
                "ConditionBrowseBranchName":"Symptoms and General Pathology"
              },{
                "ConditionBrowseBranchAbbrev":"Rare",
                "ConditionBrowseBranchName":"Rare Diseases"
              }
            ]
          }
        }
      }
    }
  }
}