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Protocol Details

Phase 1/2 Trial of Base Editing for Mutation Repair in Hematopoietic Stem & Progenitor Cells for X-linked Chronic Granulomatous Disease

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Institute of Allergy and Infectious Diseases (NIAID)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male
Min Age: 18 Years
Max Age: 75 Years

Referral Letter Required


Population Exclusion(s)



base editing;
Gene Editing

Recruitment Keyword(s)



Chronic Granulomatous Disease (CGD);
X-Linked Chronic Granulomatous Disease

Investigational Drug(s)

Base-edited hematopoietic stem and progenitor cells (BE HSPCs)

Investigational Device(s)



Biological/Vaccine: Base-edited hematopoietic stem and progenitor cells
Drug: Busulfan
Drug: Palifermin
Drug: Filgrastim
Drug: Plerixafor

Supporting Site

National Institute of Allergy and Infectious Diseases


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. This places them at risk of developing infections that may be life-threatening. Stem cell transplant can cure CGD but transplanting stem cells donated by other people can have serious complications. In addition, not everyone has a matched donor. Another approach is a type of gene therapy that involves base-editing to correct the mutation in a person s own stem cells. Researchers want to know if the base-edited stem cells can improve the white cells' functioning and result in fewer CGD-related infections.


To learn if base-edited stem cells will improve white blood cells' ability to fight against infections in people with CGD.


Males aged 18 years and older with X-linked CGD.


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.

Follow-up visits will continue for 15 years.

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->= 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 agent manufacturing.

-History of at least one prior serious infection or inflammatory complication requiring hospitalization despite conventional therapy.

-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.


Individuals meeting any of the following criteria will be excluded from study participation:

-Untreated, acute infection.

-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 abnormlaties 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.

-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.

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Komor AC, Badran AH, Liu DR. Editing the Genome Without Double-Stranded DNA Breaks. ACS Chem Biol. 2018 Feb 16;13(2):383-388. doi: 10.1021/acschembio.7b00710. Epub 2017 Oct 9. PMID: 28957631; PMCID: PMC5891729.

Kuhns DB, Alvord WG, Heller T, Feld JJ, Pike KM, Marciano BE, Uzel G, DeRavin SS, Priel DA, Soule BP, Zarember KA, Malech HL, Holland SM, Gallin JI. Residual NADPH oxidase and survival in chronic granulomatous disease. N Engl J Med. 2010 Dec 30;363(27):2600-10. doi: 10.1056/NEJMoa1007097. PMID: 21190454; PMCID: PMC3069846.

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Principal Investigator

Referral Contact

For more information:

Suk S. De Ravin, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)
NIHBC 10 - CRC BG RM 5-3816
(301) 496-6772

Suk S. De Ravin, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)
NIHBC 10 - CRC BG RM 5-3816
(301) 496-6772

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: TTY Users Dial 7-1-1

Clinical Trials Number:


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