Base-Edited Hematopoietic Stem/Progenitor Cell Gene Therapy for Treatment of CXCR4-WHIM

Part of paid clinical trials in Bethesda, Maryland.

Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Study ID
NCT07775313
Phase
PHASE1/PHASE2
Status
Enrolling By Invitation

Conditions

  • Hypogammaglobulinemia
  • Immunodeficiency
  • Myelokathexis
  • WHIM
  • Warts

Eligibility Criteria

Sex
ALL
Age
3 Years - 75 Years
Healthy Volunteers
Not accepted

Interventions

  • Busulfan — DRUG
    Myeloid conditioning agent, administered once daily x 2 days, targeting a total AUC of 9000 micromol\*min/L.
  • Palifermin — DRUG
    Mucositis prophylaxis agent, will be administered at 60 mcg/kg/day for 3 days before initiation of busulfan (days -6 to -4), as well as for the 3 days following study agent administration (days 1 to 3).
  • Plerixafor — DRUG
    Hematopoietic stem cell mobilizing agent necessary for the collection of the hematopoietic stem and progenitor cells (HSPCs) to create the study product.
  • Filgrastim — DRUG
    Hematopoietic stem cell mobilizing agent necessary for the collection of the hematopoietic stem and progenitor cells (HSPCs) to create the study product.
  • Base-edited hematopoietic stem and progenitor cells — BIOLOGICAL
    The study cell product is base edited autologous HSPCs which will be administered as a one-time infusion following myeloid conditioning.

Study Details

Background: Warts, hypogammaglobulinemia, infections and myelokathexis syndrome (WHIMs) is a rare disorder that affects the immune system. People with WHIMs can have severe infections all over their body. WHIMs is caused by a mutation in the CXCR4 gene. Treatment with drugs can help control the infections but does not cure the disorder. Researchers want to try a treatment where they collect stem cells from a person with WHIMS, use base-editing to replace the bad gene with a healthy version, and return the new cells to the person. This could cure WHIMs. Objective: To test a treatment using base-edited stem cells in people with WHIMs. Eligibility: People aged 3 years and older with WHIMs. Design: The study has 4 stages. Stage 1: Screening. Participants will be screened at 1 or more visits. They will have a physical exam with blood tests. A sample of tissue and fluid (biopsy) will be taken from the bone marrow in the hip. Stage 2: Apheresis. Blood will be taken from the body through a needle; the blood will pass through a machine that separates out the stem cells. The remaining blood will be returned to the body through a different needle. The collected stem cells will undergo gene editing. Stage 3: Treatment. Participants will stay in the hospital for about 4 weeks. They will receive 3 drugs to prepare their body for the procedure. Then the edited stem cells will be returned to their bloodstream. They will stay in the hospital until they recover. Stage 4: Follow-up. Participants will have 8 follow-up visits over 5 years. Long-term visits will continue for 15 years.

Key Dates

First listed
Aug 20, 2026
Start date
Sep 28, 2026
Status verified
Sep 2026
Primary completion
Dec 31, 2031
Completion
Dec 31, 2033

Study Design

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

Arms

  • Experimental: Single arm study
    The study cell product is base edited autologous HSPCs which will be administered as a one-time infusion following myeloid conditioning using busulfan.

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 ]

Locations (1)

FacilityCityStateZIPSite coordinators
National Institutes of Health Clinical CenterBethesdaMaryland20892-

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National Institutes of Health Clinical Center· Bethesda, MD

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