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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2016 by Genethon
Information provided by (Responsible Party):
Genethon Identifier:
First received: May 14, 2013
Last updated: February 1, 2016
Last verified: January 2016

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.

Condition Intervention Phase
X-Linked Chronic Granulomatous Disease
Genetic: X vivo gene therapy
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II, Non Randomized, Multicenter, Open-label Study of g1xcgd (Lentiviral Vector Transduced cd34+ Cells) in Patients With X-linked Chronic Granulomatous Disease

Resource links provided by NLM:

Further study details as provided by Genethon:

Primary Outcome Measures:
  • Safety of the procedure as measured by the incidence of adverse events [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
  • Restoration and stability over time of the NADPH functioning granulocytes assessed by a DHR test [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Normalisation of nutritional status, growth, development, severe infection and/or inflammatory complication which recommended patient's inclusion [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Percentage of transduced CD34+ haematopoietic cells infused and of blood cells over time [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Immunological reconstitution [ Time Frame: 24 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: February 2013
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Open label
X vivo gene therapy
Genetic: X vivo gene therapy
Transplantation of patient's autologous CD34+ cells transduced with lentiviral vector containing XCGD gene


Ages Eligible for Study:   24 Months and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Male X-CGD patients
  • Molecular diagnosis confirmed by DNA sequencing
  • At least one ongoing or resistant severe infection and/or inflammatory complications requiring hospitalisation despite conventional therapy
  • No HLA-matched donor available after 3 months search

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01855685

University Hospital Frankfurt and Institute for Biomedical Research, Georg-Speyer-Haus Active, not recruiting
Frankfurt, Germany
University Children's Hospital Zürich Active, not recruiting
Zurich, Switzerland, CH-8032
United Kingdom
Great Ormond Street Hospital NHS Foundation Trust Recruiting
London, United Kingdom
Contact: Adrian THRASHER, MD, Phd    + 44 (0)2079052292   
Sponsors and Collaborators
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
  More Information

Responsible Party: Genethon Identifier: NCT01855685     History of Changes
Other Study ID Numbers: G1XCGD.01 
Study First Received: May 14, 2013
Last Updated: February 1, 2016
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
Switzerland: Swissmedic
Germany: Paul-Ehrlich-Institut

Keywords provided by Genethon:

Additional relevant MeSH terms:
Granulomatous Disease, Chronic
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Hematologic Diseases
Immune System Diseases
Immunologic Deficiency Syndromes
Leukocyte Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Pathologic Processes
Phagocyte Bactericidal Dysfunction processed this record on May 24, 2016