Gene Therapy for X-linked Chronic Granulomatous Disease

NCT02757911 | Terminated Phase 1

• 1 other identifier: G1XCGD.02
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

X-linked chronic granulomatous disease (X-CGD) is a rare genetic disorder, which affects boys. It is a primary immunodeficiency disorder which results from an inability of the white blood cells called phagocytic cells (or phagocytes) to kill invading bacteria and fungi. These cells have difficulty forming the free radicals (most importantly the superoxide radical due to defective phagocyte NADPH oxidase complex) which are important in the killing of ingested pathogens. In X-CGD (which accounts for two thirds of CGD patients), the defect lies in a gene which makes up a critical part of the NADPH-oxidase complex (the catalytic subunit; gp91-phox protein). Therefore they kill bacteria and fungi poorly, and the patients suffer from severe and recurrent infections. This also results in inflammation which can damage parts of the body such as the lung and gut. In many cases, patients can be adequately protected from infection by constant intake of antibiotics. However, in others, severe life-threatening infections break through. In some cases, inflammation in the bowel or urinary systems results in blockages which cannot be treated with antibiotics, and which may require the use of other drugs such as steroids. Development of curative treatments for CGD is therefore of great importance.

Conditions

X-Linked Chronic Granulomatous Disease

Keywords

XCGD

Outcome Measures

Primary Outcomes (2)

• Safety as measured by the incidence of adverse events

  60 months

• Restoration and stability over time of the NADPH functioning granulocytes assessed by a Dihydrorhodamine (DHR) flow cytometry test

  12 months

Secondary Outcomes (3)

• Clinical improvement

  60 months

• Percentage of transduced CD34+ haematopoietic cells infused and of blood cells over time

  60 months

• Immunological reconstitution

  60 months

Study Arms (1)

open label

EXPERIMENTAL

X vivo gene therapy

Genetic: X vivo gene therapy

Interventions

X vivo gene therapy GENETIC

Transplantation of patient's autologous CD34+ cells transduced with lentiviral vector containing XCGD gene. The investigational product is patient-specific and corresponds to autologous CD34+ cells transduced ex vivo with the G1XCGD vector. These transduced cells will be cryopreserved until safety testing and infusion into the patient.

open label

Eligibility Criteria

• Age: 24 Months+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male X-CGD patients \>23 months of age. Youngest patients (\>1 month and ≤ 23 months) may be enrolled at physician's appreciation; in this case mobilization of peripheral HSC may be replaced by two bone marrow harvests.
• Molecular diagnosis confirmed by DNA sequencing and supported by laboratory evidence for absent or reduction \> 70% of the biochemical activity of the NAHPD-oxidase.
• At least one ongoing or resistant or at high risk of relapse severe infection and/or inflammatory complications requiring hospitalisation despite conventional therapy.
• No HLA-matched donor available after 3 months search, unless the risk of waiting for a potential match or for performing an allogeneic transplant is considered unacceptable.
• No co-infection with Human Immunodeficiency Virus (HIV) or hepatitis B virus (HBs Ag positive) or hepatitis C virus (anti-HCV Ab positive).
• Written informed consent for adult patient.
• Parental/guardian and where appropriate child's signed consent/assent.

You may not qualify if:

• /10 HLA identical (A, B, C, DR, DQ) family or unrelated.
• Contraindication for leukapheresis (anaemia Hb \<8g/dl, cardiovascular instability, severe coagulopathy).
• Contraindication for administration of conditioning medication and any component of the Investigational Medicinal Product (IMP) preparation.
• Administration of gamma interferon within 30 days before the infusion of transduced autologous CD34+ cells.
• Participation in another experimental therapeutic protocol within 6 months prior to baseline and during the study period.
• Any other condition that, in the opinion of the Investigator, may compromise the safety or compliance of the patient or would preclude the patient from successful completion of the study.
• Patient/Parent/Guardian unable or unwilling to comply with the protocol requirements.

Sponsors & Collaborators

• Genethon: lead

Study Sites (1)

Hôpital Necker Enfants Malades

Paris, 75015, France

Location

MeSH Terms

Conditions

Granulomatous Disease, Chronic

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

• Stéphane BLANCHE, MD, PHD

  Hôpital Necker-Enfants Malades

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: April 20, 2016
• First Posted: May 2, 2016
• Study Start: June 24, 2013
• Primary Completion: September 16, 2019
• Study Completion: October 17, 2025
• Last Updated: April 13, 2026

Record last verified: 2025-10

Locations

FR (1)