Base-Edited Hematopoietic Stem/Progenitor Cell X-Linked Severe Combined Immunodeficiency Gene Therapy

Conditions

• X-SCID
• X-linked Severe Combined Immunodeficiency
• XSCID

Eligibility Criteria

Sex

MALE

Age

3 Years - 99 Years

Healthy Volunteers

Not accepted

Interventions

• Plerixafor — GENETIC
  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: As is standard practice prior to busulfan conditioning, IV infusion of keratinocyte growth factor (palifermin) will be administered at 60 micrograms/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).
• Busulfan — DRUG
  Transplant Conditioning Agent: An alkylating chemotherapy drug to enhance engraftment of the study agent (base-edited stem cells). For this study, busulfan is administered once daily (3 mg/kg) x 2 days, targeting a daily busulfan AUC of 4500-6500 micromol\*min/L or a cumulative AUC of 9000 micromol\*min/L (for the 2 days of therapy if levels are available. Busulfan will be infused over 3 hours each day as per standard clinical practice.
• Base-edited hematopoietic stem and progenitor cells — BIOLOGICAL
  Investigational/Study Agent: Base-edited autologous CD34 plus hematopoietic stem and progenitor cell product. A one-time dose \>5(SqrRoot) 10\^6 base-edited cells/kg body weight will be administered to each participant. The exact dosage depends on the number of viable cells that are repaired, cryopreserved, and thawed. The study agent will be administered by IV infusion in a volume of approximately 50 mL over about 15-30 minutes, in accordance with NIH CC DTM infusion policy.

Study Details

Background: X-linked severe combined immunodeficiency (XSCID) is a rare inherited disorder that affects the immune system. It is caused by a change in the IL2RG gene. Researchers are investigating a new type of gene therapy for people with XSCID. This technique, called base-edited stem cell transplants, involves collecting a person s own stem cells, editing the genes to repair IL2RG gene, and returning the edited cells to the person. Objective: To test base-edited stem cell transplants in people with XSCID. Eligibility: People aged 3 years and older with XSCID. Design: Participants will be screened. They will have a physical exam. They may give blood, urine, and stool samples. They may have tests of their heart and lung function. They may have fluid and cells drawn from their bone marrow. Participants will undergo apheresis. Blood will be taken from the body through a needle inserted into 1 arm. 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. Participants will be admitted to the hospital 1 week before treatment. They will receive a central line: A flexible tube will be inserted into a large vein. This tube will be used to administer drugs and draw blood during their stay. They will receive drugs to prepare their bodies for the treatment. The base-edited stem cells will be infused through the central line. Participants will remain in the hospital for at least 3 weeks while they recover. Follow-up visits will continue for 15 years.

Key Dates

Start date

May 9, 2025

Status verified

May 2026

Primary completion

Dec 31, 2034

Completion

Dec 31, 2034

Study Design

Enrollment

18 participants (estimated)

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Arms

• Experimental: Single Arm Study

Primary Outcome Measure

Quantify frequency and severity of adverse events (AEs) related to study agent from infusion to 12 months after infusion. [ Time Frame: 12 months ]

Locations (1)

Find similar trials in Bethesda, MD

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• Natural History Study of SCID Disorders
  Enrolling By Invitation · National Institute of Allergy and Infectious Diseases (NIAID) · Birmingham, Alabama