Part B- G1X-CGD (Lentiviral Vector Transduced CD34+ Cells) in Patients With X-Linked Chronic Granulomatous Disease

NCT07113743 | Enrolling By Invitation Phase 1 FDA Drug

• 2 other identifiers: 10000186000186-I
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Background: X-Linked Chronic Granulomatous Disease (X-CGD) is caused by a gene mutation that makes the immune system to not work properly. Researchers want to see if a lentiviral gene transfer treatment will have the ability to make the patient s immune system more normal, in particular reduce the risk of CGD related infections. The gene transfer takes a person s own stem cells, cultures them to put the normal gene in, then gives the cells back to the person. Objective: To test a gene transfer treatment for X-CGD. Eligibility: Participants aged 3-60 with X-CGD Design: Participants will be screened under protocol 05-I-0123. They will undergo: Medical history Physical exam Heart tests Imaging tests, as needed Blood tests Lung function tests, as needed Dental and audiology exams, if needed Quality of life questionnaire Bone marrow aspiration. A needle will be inserted into the hip bone or breastbone to collect bone marrow. Some screening tests will be repeated during the study. Participants will have an apheresis procedure under protocol 94-I-0073. Stem cells will be collected. Participants will get a series of drugs to prepare them for the gene transfer. Participants will stay at the NIH Clinical Center for a little over a month. They will get a central line. It is a large intravenous (IV) catheter that is placed into a vein of the neck, chest, or arm. They will get chemotherapy and their corrected stem cells through their IV line. Participants will have 12 follow-up outpatient visits in the 2 years after their gene transfer, as well as visits with their local doctor. Then they will enroll in another study for long-term follow-up visits that will last for 13 years....

Conditions

Chronic Granulomatous Disease (CGD)

Keywords

Gene Therapy; UCLA; CGD

Outcome Measures

Primary Outcomes (2)

• Safety

  1\) The primary safety objective of this procedure will be assessed by recording the incidence of adverse events. a) Record clinical adverse events and clinically significant laboratory abnormalities. b) Evaluate overall incidence of adverse events for the study as a whole. c) Monitor the incidence of serious adverse events.

  Throughout the study

• Efficacy

  The primary efficacy objective of this study will be determined by measuring the percentage of subjects who have \>= 10% oxidase positive granulocytes by DHR flow cytometry at month 6 and 12 after transplant.

  6 months and 1 year

Secondary Outcomes (3)

• Assess immunological reconstitution

  Week 4, 5, 6, 7, 8, 10, 12 and months 6, 9, 12, 18 and 24 months.

• Assess HSC transduction and engraftment

  Week 4, 6, 7, 8, 10, 12 and month 6, 9, 12, 18 and 24)

• Assess health by

  1, 2, 3, 6, 9, 12, 18, and 24 months, compared to baseline

Study Arms (1)

X-linked CGD

EXPERIMENTAL

Non-randomized single arm

Drug: Busulfan; Drug: Tocilizumab; Drug: Eltrombopag; Drug: Sirolimus; Other: pCCLChimGp91lentiviral vector containing the human gp91 phox (CYBB) gene

Interventions

Busulfan DRUG

Conditioning drug

X-linked CGD

Tocilizumab DRUG

Monoclonal Antibody

X-linked CGD

Sirolimus DRUG

Post transplant immunosuppressant drug

X-linked CGD

pCCLChimGp91lentiviral vector containing the human gp91 phox (CYBB) gene OTHER

Intervention Infusion on Day 0

X-linked CGD

Eltrombopag DRUG

Thrombopoietin Receptor Agonist

X-linked CGD

Eligibility Criteria

• Age: 3 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• In order to be eligible to participate in this study, an individual must meet all of the following criteria:
• Must have confirmed molecular diagnosis of X-linked CGD confirmed by deoxyribonucleic acid (DNA) sequencing and supported by laboratory evidence for absent or reduction \>90% of the biochemical activity of the NADPH-oxidase.
• At least 1 prior ongoing or refractory severe infection and/or inflammatory complications requiring hospitalization despite conventional therapy.
• No 10/10 HLA-matched donor available after initial search of National Marrow Donor Program (NMDP) registries within the last year.
• Must weigh at least 15 kg.
• Male or female, and must be at least 3 years of age but no older than 60.
• Parent/guardian must be willing to sign and date informed consent form for child and where appropriate, child may sign assent.
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Ability to take oral medication and be willing to adhere to the prophylactic regimen.
• Apheresis of patients for the hematopoietic stem cells collected as a part of this protocol will be performed according to the Standard of Care apheresis practices established in the NIH CC Department of Transfusion Medicine for such procedures.
• For apheresis, pediatric patients:
• Must weigh at least 15 kg body weight;
• Preserved renal function (creatinine \<=2.5 mg/dL; \<=3+ proteinuria); preserved hepatic function (bilirubin \<=2.0 mg/dl);
• Must be negative for co-infection with human immunodeficiency virus (HIV) or hepatitis B virus (HBsAg positive) or hepatitis C virus (HCV ribonucleic acid (RNA) positive), adenovirus, parvovirus B 19 or toxoplasmosis or mycobacterial infection (prior or current).
• For females of reproductive potential, must agree to use of 2 highly effective contraception throughout study participation and for at least 3 months after the study.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Patient/Parent/Guardian unable or unwilling to comply with the protocol requirements.
• Contraindication for leukapheresis (anemia Hb \<8 g/dl, cardiovascular instability, severe coagulopathy).
• Patients who are unable to lie prone during the bone marrow harvesting procedure (in the case of bone marrow harvest, contraindication to general anesthesia).
• Have a 10/10 HLA identical (A,B,C,DR,DQ) family or unrelated adult donor unless there is deemed to be an unacceptable risk associated with an allogeneic procedure.
• Tested positive (definitive) for the presence of multiple types (2 or more) of anti-platelet antibodies.
• Altered organ function as outlined below observed within 8 weeks of entering this trial.
• a. Hematologic
• i. Anemia (hemoglobin \< 8 g/dl).
• ii. Neutropenia (absolute granulocyte count \<1,000/mm3 ).
• iii. Thrombocytopenia (platelet count \< 150,000/mm3).
• iv. Prothrombin Time (PT) INR or Partial thromboplastin time (PTT) \> 2 X the upper limits of normal (ULN) (patients with a correctable deficiency controlled on medication will not be excluded).
• v. Cytogenetic abnormalities known to be associated with hematopoietic defect on peripheral blood or bone marrow.
• b. Infectious
• i. Evidence of infection with HIV-1 and -2, Hepatitis B, Hepatitis C, adenovirus, parvovirus B 19 or toxoplasmosis within 8 weeks prior to mobilization/apheresis or bone marrow harvest. Cytomegalovirus (CMV) infection is allowable as long as the infection is under control.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Granulomatous Disease, Chronic

Interventions

Busulfan; tocilizumab; eltrombopag; Sirolimus; Genes

Condition Hierarchy (Ancestors)

Phagocyte Bactericidal Dysfunction; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunologic Deficiency Syndromes; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Macrolides; Lactones; Genome Components; Genome; Genetic Structures; Genetic Phenomena

Study Officials

• Elizabeth M Kang, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2025
• First Posted: August 11, 2025
• Study Start: September 10, 2025
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2029
• Last Updated: May 1, 2026

Record last verified: 2026-04-01

Locations

US (1)