protocolSection identificationModule nctId: NCT06297486, orgStudyIdInfo id: SPK-8011-302, secondaryIdInfos id: 2023-504537-46, type: EUDRACT_NUMBER, briefTitle: Study of a Gene Therapy Treatment for Hemophilia A, acronym: KEYSTONE 1, statusModule overallStatus: RECRUITING, startDateStruct date: 2024-03-13, primaryCompletionDateStruct date: 2027-05, completionDateStruct date: 2035-09-04, studyFirstPostDateStruct date: 2024-03-07, lastUpdatePostDateStruct date: 2024-04-18, sponsorCollaboratorsModule leadSponsor name: Spark Therapeutics, Inc., class: INDUSTRY, descriptionModule briefSummary: The purpose of this study is to evaluate the efficacy of SPK-8011 in preventing bleed episodes compared with FVIII prophylaxis in participants with hemophilia A without FVIII inhibitors on routine FVIII prophylaxis., conditionsModule conditions: Hemophilia A, designModule studyType: INTERVENTIONAL, phases: PHASE3, designInfo allocation: NON_RANDOMIZED, interventionModel: PARALLEL, interventionModelDescription: Participants will be assigned into one of three cohorts, each receiving the same study treatment., primaryPurpose: TREATMENT, maskingInfo masking: NONE, enrollmentInfo count: 85, type: ESTIMATED, armsInterventionsModule interventions name: SPK-8011, outcomesModule primaryOutcomes measure: Annualized Bleed Rate (ABR) for All Bleeds [Cohort A], secondaryOutcomes measure: Median FVIII: C levels [Cohort A], secondaryOutcomes measure: ABR for treated bleeds [Cohort A], secondaryOutcomes measure: Percentage of Participants with ABR=0 for all bleeds; treated bleeds; treated spontaneous bleeds; and treated joint and target joint bleeds [Cohort A], secondaryOutcomes measure: ABR for treated spontaneous, joint, and target joint bleeds [Cohort A], secondaryOutcomes measure: Annualized FVIII dosage [Cohort A], secondaryOutcomes measure: Proportion of Resolved Target Joints [Cohort A], secondaryOutcomes measure: Mean Change of Total Hemophilia Joint Health Score [Cohort A], secondaryOutcomes measure: FVIII:C levels over time [Cohort A], secondaryOutcomes measure: Mean ABR for all bleeds and treated bleeds [Cohort C], secondaryOutcomes measure: FVIII: C levels over time from Week 26 [Cohort C], secondaryOutcomes measure: Proportion of Participants Who Receive IV Methylprednisolone (IVMP) Prior to Week 8 (Early IVMP) [Cohorts A, B, C], secondaryOutcomes measure: Proportion of Participants Who Receive Secondary Oral Immunomodulation [Cohorts A, B, C], secondaryOutcomes measure: Median Time to First Immunomodulation-related Corticosteroid Dose [Cohorts A, B, C], secondaryOutcomes measure: Median Duration of Secondary Oral Immunomodulation [Cohorts A, B, C], secondaryOutcomes measure: Proportion of Participants with FVIII Inhibitor Development [Cohorts A, B, C], secondaryOutcomes measure: Proportion of participants with Treatment-related AEs of ALT Elevation [Cohorts A, B, C], secondaryOutcomes measure: Proportion of participants with treatment-related AEs of Infusion Reaction [Cohorts A, B, C], secondaryOutcomes measure: Number of participants with abnormal physical exam findings, abnormal vital signs, and abnormal selected clinical laboratory test results [Cohorts A, B, C], secondaryOutcomes measure: Proportion of participants with AEs and SAEs [Cohorts A, B, C], secondaryOutcomes measure: Proportion of participants with AESIs [Cohorts A, B, C], eligibilityModule sex: MALE, minimumAge: 18 Years, stdAges: ADULT, stdAges: OLDER_ADULT, contactsLocationsModule locations facility: Orthopaedic Institute for Children/Orthopaedic Hemophilia Treatment Center, status: RECRUITING, city: Los Angeles, state: California, zip: 90007, country: United States, contacts name: Doris Quon, MD, PhD, role: CONTACT, geoPoint lat: 34.05223, lon: -118.24368, locations facility: Kaiser Permanente-Oakland Medical Center, status: RECRUITING, city: Oakland, state: California, zip: 94611, country: United States, contacts name: Tatjana Kolevska, MD, role: CONTACT, geoPoint lat: 37.80437, lon: -122.2708, locations facility: Kaiser Permanente-Roseville Medical Center, status: RECRUITING, city: Roseville, state: California, zip: 95661, country: United States, contacts name: Tatjana Kolevska, MD, role: CONTACT, geoPoint lat: 38.75212, lon: -121.28801, locations facility: Kaiser Permanente -Sacramento Medical Center, status: RECRUITING, city: Sacramento, state: California, zip: 95814, country: United States, contacts name: Tatjana Kolevska, MD, role: CONTACT, geoPoint lat: 38.58157, lon: -121.4944, locations facility: Kaiser Permanente -San Francisco Medical Center, status: RECRUITING, city: San Francisco, state: California, zip: 94115, country: United States, contacts name: Tatjana Kolevska, MD, role: CONTACT, geoPoint lat: 37.77493, lon: -122.41942, locations facility: University of California - San Francisco, status: RECRUITING, city: San Francisco, state: California, zip: 94143, country: United States, contacts name: Andrew Leavitt, MD, role: CONTACT, geoPoint lat: 37.77493, lon: -122.41942, locations facility: Kaiser Permanente- Santa Clara Medical Center, status: RECRUITING, city: Santa Clara, state: California, zip: 94115, country: United States, contacts name: Tatjana Kolevska, MD, role: CONTACT, geoPoint lat: 37.35411, lon: -121.95524, locations facility: Kaiser Permanente-Vallejo Medical Center, status: RECRUITING, city: Vallejo, state: California, zip: 94589, country: United States, contacts name: Tatjana Kolevska, MD, role: CONTACT, geoPoint lat: 38.10409, lon: -122.25664, locations facility: Kaiser Permanente -Walnut Creek Medical Center, status: RECRUITING, city: Walnut Creek, state: California, zip: 94596, country: United States, contacts name: Tatjana Kolevska, MD, role: CONTACT, geoPoint lat: 37.90631, lon: -122.06496, hasResults: False