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

Summary

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.

Conditions

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

Interventions

GENETIC

Plerixafor

Stem Cell Mobilizing Agent: Subcutaneous administration for 2 consecutive days to improve stem cell collection.

DRUG

Filgrastim

Stem Cell Mobilizing Agent: Subcutaneous administration for 6 consecutive days. It is necessary to mobilize stem cells for collection.

DRUG

Palifermin

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).

DRUG

Busulfan

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.

BIOLOGICAL

Base-edited hematopoietic stem and progenitor cells

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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)

  lead NIH

Principal Investigators

• Suk S De Ravin, M.D. · National Institute of Allergy and Infectious Diseases (NIAID)

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

3 Years

Max Age

99 Years

Sex

MALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-05-09

Primary Completion

2034-12-31

Completion

2034-12-31

FDA Drug

Yes

Countries

• United States

Study Locations