protocolSection identificationModule nctId: NCT06325709, orgStudyIdInfo id: 10001580, secondaryIdInfos id: 001580-I, briefTitle: Base Editing for Mutation Repair in Hematopoietic Stem & Progenitor Cells for X-Linked Chronic Granulomatous Disease, statusModule overallStatus: ENROLLING_BY_INVITATION, startDateStruct date: 2024-04-17, primaryCompletionDateStruct date: 2032-12-31, completionDateStruct date: 2032-12-31, studyFirstPostDateStruct date: 2024-03-22, lastUpdatePostDateStruct date: 2024-04-26, sponsorCollaboratorsModule leadSponsor name: National Institute of Allergy and Infectious Diseases (NIAID), class: NIH, descriptionModule briefSummary: Background:Chronic granulomatous disease (CGD) is a rare immune disorder caused by a mutation in the CYBB gene. People with CGD have white blood cells that do not work properly. This places them at risk of developing infections that may be life-threatening. Stem cell transplant can cure CGD but transplanting stem cells donated by other people can have serious complications. In addition, not everyone has a matched donor. Another approach is a type of gene therapy that involves base-editing to correct the mutation in a person s own stem cells. Researchers want to know if the base-edited stem cells can improve the white cells' functioning and result in fewer CGD-related infections.Objective:To learn if base-edited stem cells will improve white blood cells' ability to fight against infections in people with CGD.Eligibility:Males aged 18 years and older with X-linked CGD.Design:This is a non-randomized study. Participants with the specific mutation under study will be screened during the initial phase.During the development phase, participants will undergo apheresis to collect stem cells for base-editing correction of the mutation.During the treatment phase, participants will receive the base-edited cells after chemotherapy with busulfan. Participants will remain in the hospital until their immunity recovers.Follow-up visits will continue for 15 years., conditionsModule conditions: Chronic Granulomatous Disease (CGD), conditions: X-Linked Chronic Granulomatous Disease, designModule studyType: INTERVENTIONAL, phases: PHASE1, phases: PHASE2, designInfo allocation: NA, interventionModel: SINGLE_GROUP, primaryPurpose: TREATMENT, maskingInfo masking: NONE, enrollmentInfo count: 10, type: ESTIMATED, armsInterventionsModule interventions name: Base-edited hematopoietic stem and progenitor cells, interventions name: Busulfan, interventions name: Palifermin, interventions name: Filgrastim, interventions name: Plerixafor, outcomesModule primaryOutcomes measure: To evaluate the safety of base-edited autologous CD34+ cells, primaryOutcomes measure: To evaluate the efficacy of base-edited autologous CD34+ cells, secondaryOutcomes measure: Evaluate the efficiency of base-editing., secondaryOutcomes measure: Evaluate the engraftment capability of base-edited hematopoietic stem progenitor cells., secondaryOutcomes measure: Evaluate the efficiency in restoring gp91phox expression., secondaryOutcomes measure: Evaluate efficacy in restoring NADPH oxidase function., secondaryOutcomes measure: Evaluate clinical efficacy, secondaryOutcomes measure: Evaluate the stability of gene correction, eligibilityModule sex: MALE, minimumAge: 18 Years, maximumAge: 75 Years, stdAges: ADULT, stdAges: OLDER_ADULT, contactsLocationsModule locations facility: National Institutes of Health Clinical Center, city: Bethesda, state: Maryland, zip: 20892, country: United States, geoPoint lat: 38.98067, lon: -77.10026, hasResults: False