Gene Therapy for X-linked Chronic Granulomatous Disease

April 5, 2023 updated by: Genethon

A Phase I/II, Non Randomized, Monocentric Open-label Study of Autologous CD34+ Cells Transduced With the G1XCGD Lentiviral Vector in Patients With X-Linked Chronic Granulomatous Disease

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.

Study Overview


Active, not recruiting

Intervention / Treatment

Study Type


Enrollment (Actual)



  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Paris, France, 75015
        • Hopital Necker Enfants Malades

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers


Genders Eligible for Study



Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 10/10 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: open label
X vivo gene therapy
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Safety as measured by the incidence of adverse events
Time Frame: 60 months
60 months
Restoration and stability over time of the NADPH functioning granulocytes assessed by a Dihydrorhodamine (DHR) flow cytometry test
Time Frame: 12 months
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical improvement
Time Frame: 60 months
Assessed by: complete physical examination to assess the normalisation of nutritional status, the growth, the development, the decrease in the severity of the infection and/or inflammatory complication at inclusion.
60 months
Percentage of transduced CD34+ haematopoietic cells infused and of blood cells over time
Time Frame: 60 months
60 months
Immunological reconstitution
Time Frame: 60 months
Assessed by: evidence of restored neutrophil functionality (DRH test), expression of gp91phox protein by flow cytometry and immunity against bacterial and fungal infections over time.
60 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.



  • Principal Investigator: Stéphane BLANCHE, MD, PHD, Hopital Necker-Enfants Malades

Study record dates

These dates track the progress of study record and summary results submissions to Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2016

Primary Completion (Anticipated)

June 1, 2034

Study Completion (Anticipated)

June 1, 2034

Study Registration Dates

First Submitted

April 20, 2016

First Submitted That Met QC Criteria

April 27, 2016

First Posted (Estimate)

May 2, 2016

Study Record Updates

Last Update Posted (Actual)

April 6, 2023

Last Update Submitted That Met QC Criteria

April 5, 2023

Last Verified

April 1, 2023

More Information

This information was retrieved directly from the website without any changes. If you have any requests to change, remove or update your study details, please contact As soon as a change is implemented on, this will be updated automatically on our website as well.

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