Actively Recruiting

Phase 1
Phase 2
Age: 18Years - 75Years
MALE
NCT06325709

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

Led by National Institute of Allergy and Infectious Diseases (NIAID) · Updated on 2026-04-06

10

Participants Needed

1

Research Sites

454 weeks

Total Duration

On this page

AI-Summary

What this Trial Is About

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.

CONDITIONS

Official Title

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

Who Can Participate

Age: 18Years - 75Years
MALE

Eligibility Criteria

Eligible

You may qualify if you...

  • Male patients aged 18 years or older
  • Confirmed CYBB c.676 C>T mutation
  • Clinically stable and eligible for apheresis and conditioning chemotherapy
  • At least 5 million cryopreserved cells per kilogram body weight available for product manufacturing
  • History of at least one serious infection or inflammatory complication requiring hospitalization despite conventional therapy
  • Poor prognosis as assessed by a qualified clinical investigator
  • Able and willing to use highly effective contraception during the study and for 6 months after infusion, with partner's agreement
Not Eligible

You will not qualify if you...

  • Untreated, acute infection
  • Elevated anti-gp91 specific autoantibodies above 2 times upper limit of normal
  • Elevated anti-gp91 specific T cells more than 10-fold
  • Positive anti-platelet antibody screening with ongoing brain infection or unsafe for study participation after hematology consultation
  • Known allergy to busulfan or any study product component
  • Contraindications to busulfan administration
  • Current or prior hematologic malignancy
  • Chronic infections deemed unsafe by infectious disease consultant
  • Unsafe cardiac or neurological abnormalities
  • Childhood malignancy in patient or first-degree relative or known cancer predisposition genotype
  • Unsafe hematological parameters for apheresis or above Grade 2 adverse events until improved
  • Liver dysfunction with ALT, AST, or bilirubin above specified limits
  • Kidney dysfunction with elevated serum creatinine or reduced creatinine clearance
  • Coagulation dysfunction with elevated INR or PTT (except controlled anticoagulation therapy)
  • Uncontrolled hypertension with systolic BP 140-159 mm Hg or diastolic BP 90-99 mm Hg
  • Abnormal blood chemistries including hyperkalemia, hypokalemia requiring intervention, hypercalcemia, or hypocalcemia
  • Cytogenetic abnormalities in bone marrow aspirate
  • Pulmonary dysfunction with FEV1 less than 25% predicted
  • Previous gene therapy or gene editing treatment
  • Previous receipt of non-HLA matched donor granulocyte transfusions
  • Any condition compromising safety, compliance, or chances of study completion as judged by investigators

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

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Trial Site Locations

Total: 1 location

1

National Institutes of Health Clinical Center

Bethesda, Maryland, United States, 20892

Actively Recruiting

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Research Team

S

Suk S De Ravin, M.D.

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NA

Model

SINGLE_GROUP

Primary Purpose

TREATMENT

Number of Arms

1

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