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

Recruiting now · Phase 1/Phase 2

Conditions studied: Chronic Granulomatous Disease (CGD), X-Linked Chronic Granulomatous Disease

In brief

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. Researchers want to know if gene therapy using the patient's own 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 first receive Campath (alemtuzumab) to reduce the risk of an immune response to the new protein expressed by the base-edited cells. This will be followed by conditioning chemotherapy with busulfan and subsequent infusion of the base-edited stem cells. Participants will be maintained on sirolimus to further reduce the risk of an immune response to the new protein expressed by the base-edited cells. Follow-up visits will continue for 15 years....

Key facts

Study ID

NCT06325709

Run by

National Institute of Allergy and Infectious Diseases (NIAID)

People needed

15

Starts

2024-04-17

Expected to finish

2032-12-31

Last updated by the study team

2026-08-07

Who can join

Age: 18 and older, up to 75. Sex: male. Healthy volunteers: not accepted.

You may not qualify if…

• Individuals meeting any of the following criteria will be excluded from study participation:
• Untreated, acute infection.
• Elevated anti-gp91 specific autoantibodies >2 x ULN
• Elevated anti-gp91 specific T cells (>10 fold)
• Anti-platelet antibody screening with >1 anti-platelet antibody positive in the presence of an ongoing brain infection; OR >1 anti-platelet antibody positive and considered unsafe for study participation after consultation with hematology specialist.
• Known hypersensitivity to busulfan or any component of the product.
• Contraindications for administration of busulfan.
• Any current or pre-existing hematologic malignancy.
• Chronic infections that are considered unsafe for participation in the study by Infectious Disease Consultant.
• Cardiac abnormalities and neurological abnormalities that are deemed unsafe to participate in the study.
• Childhood malignancy (occurring before 18 years of age) in the patient or a first degree relative, or previously diagnosed known genotype of the participant conferring a predisposition to cancer (no DNA or other testing for cancer predisposition genes will be performed as part of the screen for this protocol).
• Hematological parameters unsafe for apheresis or above Grade 2 Common Terminology Criteria for Adverse Events (CTCAE) criteria until improved.
• Hepatic dysfunction- alanine aminotransferase (ALT >3.0 - 5.0 x upper limit of normal [ULN]), aspartate aminotransferase (AST >3.0 - 5.0 x ULN), bilirubin (>1.5 - 3.0 x ULN).
• Renal dysfunction-serum creatinine >1.5 - 3.0 x ULN or creatinine clearance 59-30 mL/min/1.73 m\^2.
• Coagulation dysfunction- Prothrombin INR or Partial thromboplastin time >2 x ULN (patients on controlled anticoagulation agents will not be excluded for therapeutic levels).
• Uncontrolled hypertension- Systolic BP 140-159 mm Hg or diastolic BP 90-99 mm Hg.
• Abnormal blood chemistries- Hyperkalemia (K >5.5 - 6.0 mmol/L), Hypokalemia (<LLN - 3.0 mmol/L and requiring intervention); OR Hypercalcemia (corrected serum calcium >11.5 - 12.5 mg/dL), Hypocalcemia (corrected serum calcium <8.0 -7.0 mg/dL)
• These values exclude false abnormalities secondary to hemolysis.
• Cytogenetic abnormalities evidenced on bone marrow aspirate.
• Pulmonary dysfunction FEV1<25% predicted.
• Previous treatment with gene therapy or gene editing products.
• Previous receipt of non-HLA matched donor granulocyte transfusions.
• Any other condition that, in the opinion of the investigator, may unduly compromise the safety or compliance of the patient, or would make successful study completion highly unlikely.
• Unwilling to submit their information as part of the alemtuzumab (Campath(R)) Distribution Program application or the Distribution Program committee has determined the participant is not qualified to receive alemtuzumab.
• NOTE: Alemtuzumab (campath) is no longer distributed commercially. To receive product, the physician must contact the program for the participant. If the participant is not willing to consent to submit their info (demographics, contact information, and rationale for use) to the program such that we can obtain the drug, then we cannot proceed with conditioning; therefore, no gene therapy will occur on this protocol.

Where it is running

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (enrolling)

Full record on ClinicalTrials.gov

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