pCCLCHIM-p47 (Lentiviral Vector Transduced CD34 Plus Cells) in Patients With p47 Autosomal Recessive Chronic Granulomatous Disease (AR-CGD)

NCT06253507 | Enrolling By Invitation Phase 1 FDA Drug

• 2 other identifiers: 10001562001562-I
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Chronic granulomatous disease (CGD) is a genetic disorder. People with CGD are missing a gene that affects their white blood cells. White cells are part of the immune system, and people with GCD are vulnerable to many infections. Researchers want to test a new treatment to replace the missing gene that may be safer than the current treatment for CGD. Objective: To test a new type of gene therapy in people with CGD. Eligibility: People aged 3 years or older with CGD. Design: Participants will undergo apheresis: Blood will be collected through a tube attached to a needle inserted in a vein; the blood will run through a machine that separates certain cells (stem cells); the remaining blood will be returned to the body through a second needle. The participant s stem cells will be modified in a laboratory to add the gene they are missing. Participants will stay in the hospital for about 40 days. For the first 10 days, they will undergo many exams, including imaging scans and tests of their heart and lung function. They will receive drugs to prepare their bodies for the gene therapy. They will receive a "central line": A hollow tube will be inserted into a vein in the chest, with a port opening above the skin. This port will be used to draw blood and administer drugs without the need for new needle sticks. For the gene therapy, each participant s own modified stem cells will be put into their body through the port. Participants will have 8 follow-up visits over 3 years.

Conditions

p47; Chronic Granulomatous Disease; Autosomal Recessive

Keywords

p47 Phox; Autosomal Recessive; Chronic Granulomatous Disease; Gene Therapy; Lenti Vector

Outcome Measures

Primary Outcomes (1)

• To evaluate the efficacy of pCCLCHIM-p47 transduced autologous CD34+ cells treatment in p47 AR-CGD patients as measured by engraftment of genetically modified cells.

  6 months to 1 year.

Secondary Outcomes (4)

• Safety

  Length of study

• Long term Engraftment

  6, 12, 18, 24, and 36 months

• Event Free Survival

  3 years

• Clinical Efficacy and Health Assessment

  24 and 36 months

Study Arms (1)

Single arm

EXPERIMENTAL

Biological: Cryopreserved Autologous CD34+ cells transduced with pCCLCHIM-p47

Interventions

Cryopreserved Autologous CD34+ cells transduced with pCCLCHIM-p47 BIOLOGICAL

Cryopreserved autologous CD34+ cells transduced ex vivo with the pCCLCHIM-p47 vector containing the human p47phox (NCF1) gene in final formulation and container closure system, ready for intended medical use. The minimum cell dose for infusion is 3 x 10\^6 CD34+/kg.

Single arm

Eligibility Criteria

• Age: 3 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

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 genetic diagnosis of p47 AR-CGD by identification of a mutation in the responsible genes or protein analysis demonstrating lack of P47 expression and supported by laboratory evidence for absent or reduction \> 95% of the biochemical
• activity of the NADPH-oxidase.
• Must weigh at least 15 kg.
• Adult Patient must be willing to sign and date informed consent form.
• Parent/guardian must be willing to sign and date informed consent form for child and where appropriate, child may sign assent.
• State willingness to comply with all study procedures and availability for the duration of the study.
• Male or female must be at least 3 years of age.
• Do not have an appropriately HLA matched donor (related or unrelated)
• Must have had at least a history of a prior CGD related infection and/or an ongoing/refractory severe infection requiring hospitalization and/or inflammatory complications requiring hospitalization despite conventional therapy.
• Patients will be collected as per standard of care mobilization and apheresis procedures as performed at the Clinical Center. Patients will have consented onto the gene therapy study prior to collection; however products collected prior to the study for other protocols may be used as part of the back up.
• Patient must weigh at least 15 kilograms body weight.
• Normal female donors of childbearing potential may be entered if using effective contraception and having a negative serum pregnancy test within one week of beginning G-CSF administration.
• Ability to take oral medication and be willing to adhere to the prophylactic regimen.
• For females of reproductive potential, must agree to use 2 forms of highly effective contraception throughout study participation (for a minimum of 3 months after having received the genetically modified cells but preferably for the first 2 years.)

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 \<8g/dL, cardiovascular instability, severe coagulopathy, uncontrolled seizure disorder).
• Pregnancy or lactation.
• Tested positive (definitive) for the presence of multiple types (2 or more) of anti-platelet antibodies.
• Patient will be excluded if they have any of the following within 8 weeks of entering the trial.
• Hematologic
• Anemia (hemoglobin \< 8 g/dL).
• Neutropenia (absolute granulocyte count \<1,000/mm3)
• Thrombocytopenia (platelet count \< 100,000/mm3).
• Prothrombin Time (PT) 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).
• Cytogenetic abnormalities known to be associated with hematopoietic defect on peripheral blood or bone marrow.
• Infectious
• Evidence of infection with HIV-1 and -2, or active Hepatitis B, Hepatitis C, Adenovirus, Parvovirus, Toxoplasmosis, or any other uncontrolled viral infection.
• Pulmonary

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; Granulomatous Disease, Chronic, Autosomal Recessive, Cytochrome B-Positive, Type I

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

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: February 9, 2024
• First Posted: February 12, 2024
• Study Start: June 25, 2024
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): March 31, 2027
• Last Updated: February 23, 2026

Record last verified: 2026-02-17

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)