NCT06325709 Base Editing for Mutation Repair in Hematopoietic Stem & Progenitor Cells for X-Linked Chronic Granulomatous Disease

Eligibility & Interventions

Eligibility Fast-Check

Enter your details for a quick preliminary check. This does not replace medical advice.

What to Expect as a Participant

You will actively receive the study intervention — which may be a drug, biologic, device, or procedure.

Phase 1 is the earliest stage of human testing — safety and dosage are the primary focus. Visits are frequent and medical supervision is intensive. You will be among the first people to receive this treatment.

This trial targets 10 participants in total. It began in 2024-04-17 with a primary completion date of 2032-12-31.

Brief Summary

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.

Eligibility Criteria

* INCLUSION CRITERIA: -\>= 18 years of age. * Confirmed CYBB c.676 C\>T mutation. * Male patients. * Clinically stable and eligible to undergo apheresis and conditioning chemotherapy. -\>=5 x 10\^6 cryopreserved cells/kg body weight available for study product manufacturing. * History of at least one prior serious infection or inflammatory complication requiring hospitalization despite conventional therapy. * In the experience of a qualified clinical investigator, the patient has a poor prognosis. * Able and willing to use a highly effective method of contraception, AND partner has communicated her willingness through subject to do same, if engaging in potentially reproductive sex from the signing of the informed consent and for 6 months after IMP infusion. Acceptable methods of contraception include the following: * Hormonal contraception in continuously effective use by female partner. * Male or female condom with spermicide as indicated. * Diaphragm or cervical cap in consistent and effective pattern of use with a spermicide by female partner. * Intrauterine device in-situ throughout above period by female partner. EXCLUSION CRITERIA: 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.

Contact & Investigator

Frequently Asked Questions

Related Trials