Gene Therapy for X-linked Chronic Granulomatous Disease (X-CGD) (CGD)

April 5, 2023 updated by: Genethon

A Phase I/II, Non Randomized, Multicenter, 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 caused by an error in a gene that makes part of the immune system. The basic defect lies in specialised white blood cells called phagocytic cells (or phagocytes), which are responsible for protection against infection by destroying invading bacteria and fungi. They do this by pouring large amounts of substances similar to bleach onto these organisms. In CGD, there is a defect in the system that makes the bleach, called the NADPH-oxidase. In X-CGD (which accounts for two thirds of patients), the defect lies in a gene which makes up a critical part of the NADPH-oxidase (known as gp91-phox), and the cells cannot make bleach-like substances. 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

      • London, United Kingdom, NW1 2PG
        • University College London Hospital (UCLH)
      • London, United Kingdom
        • Great Ormond Street Hospital NHS Foundation Trust

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

6 months and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers


Genders Eligible for Study



Inclusion Criteria:

  • Male X-CGD patients
  • Molecular diagnosis confirmed by DNA sequencing
  • At least one prior ongoing or resistant 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 by the investigator

Exclusion Criteria:

  • Contraindication for leukapheresis
  • Contraindication for administration of conditioning medication
  • Administration of gammainterferon within 30 days before the infusion of transduced autologous CD34+ cells

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 GP91PHOX gene

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Safety of the procedure as measured by the incidence of adverse events
Time Frame: 24 months
24 months
Restoration and stability over time of the NADPH functioning granulocytes assessed by a DHR test
Time Frame: 12 months
12 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Normalisation of nutritional status, growth, development, severe infection and/or inflammatory complication which recommended patient's inclusion
Time Frame: 24 months
24 months
Percentage of transduced CD34+ haematopoietic cells infused and of blood cells over time
Time Frame: 24 months
24 months
Immunological reconstitution
Time Frame: 24 months
24 months

Collaborators and Investigators

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



  • Principal Investigator: Adrian Thrasher, MD, PHD, Great Ormond Street Hospital NHS Foundation Trust - London - UK
  • Principal Investigator: Janine Reichenbach, MD, University Children's Hospital Zürich - Switzerland
  • Principal Investigator: Hubert Serve, MD, PHD, Department of Hematology/Oncology, University Hospital Frankfurt and Institute for Biomedical Research, Georg-Speyer-Haus, Frankfurt - Germany
  • Principal Investigator: Emma Morris, MD, PHD, Royal Free Hospital / University College London Hospital (UCLH)

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)

June 24, 2013

Primary Completion (Anticipated)

September 1, 2032

Study Completion (Anticipated)

September 1, 2032

Study Registration Dates

First Submitted

May 14, 2013

First Submitted That Met QC Criteria

May 14, 2013

First Posted (Estimate)

May 16, 2013

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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