Base Editing for Mutation Repair in Hematopoietic Stem & Progenitor Cells for X-Linked Chronic Granulomatous Disease

Part of paid clinical trials in Bethesda, Maryland.

Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Study ID
NCT06325709
Phase
PHASE1/PHASE2
Status
Recruiting
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Conditions

  • Chronic Granulomatous Disease (CGD)
  • X-Linked Chronic Granulomatous Disease

Eligibility Criteria

Sex
MALE
Age
18 Years - 75 Years
Healthy Volunteers
Not accepted

Interventions

  • Plerixafor — DRUG
    Stem Cell Mobilizing Agent: Subcutaneous administration for 2 consecutive days to improve stem cell collection.
  • Filgrastim — DRUG
    Stem Cell Mobilizing Agent: Subcutaneous administration for 6 consecutive days. It is necessary to mobilize stem cells for collection.
  • Palifermin — DRUG
    Mucositis Prophylaxis Agent: Intravenous infusion of keratinocyte growth factor (Palifermin) at 60 mcg/kg/day before (Days -7 to Day -5 administration of busulfan and (Days 1 to 3) post-busulfan administration to prevent oral mucositis.
  • Busulfan — DRUG
    Transplant Conditioning Agent: An alkylating chemotherapy drug to enhance engraftment of the study agent (base-edited stem cells). Conditioning will be given intravenously over 3 days with an approximate total dose of 12mg/kg. Drug levels obtained will be obtained to achieve the targeted total busulfan AUC of 65,000 ng/mL x hr.
  • Base-edited hematopoietic stem and progenitor cells — BIOLOGICAL
    Investigational/Study Agent: Base-edited autologous CD34 plus hematopoietic stem and progenitor cell product. The product is administered intravenously as a single infusion. This product is under an IND.
  • Sirolimus — DRUG
    Immunomodulating agent: Daily oral dosing beginning Day -1 for approximately 3 to 6 months to prevent an immune response to the protein expressed by the BE HSPCs.

Study Details

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 and are at greater risk of getting infections. Gene therapy using lentivector has helped people with CGD. 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 correct the white blood cells 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. Participants will be maintained on sirolimus to prevent an immune response to the new protein expressed by the base-edited cells. Follow-up visits will continue for 15 years.

Key Dates

Start date
Apr 17, 2024
Status verified
Jan 2026
Primary completion
Dec 31, 2032
Completion
Dec 31, 2032

Study Design

Enrollment
10 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Single Arm Study

Primary Outcome Measure

To evaluate the safety of base-edited autologous CD34+ cells [ Time Frame: Initiated from the time of the infusion of base-edited cells through 2 years post-infusion ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
National Institutes of Health Clinical CenterBethesdaMaryland20892
NIH Clinical Center Office of Patient Recruitment (OPR)
[email protected]
800-411-1222
Suk See De Ravin, MD
[email protected]
(301) 496-6772

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