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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01855685
Recruitment Status : Active, not recruiting
First Posted : May 16, 2013
Last Update Posted : May 21, 2021
Information provided by (Responsible Party):

Brief Summary:

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 or disease Intervention/treatment Phase
X-Linked Chronic Granulomatous Disease Genetic: X vivo gene therapy Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : June 24, 2013
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : September 2022

Arm Intervention/treatment
Experimental: Open label
X vivo gene therapy
Genetic: X vivo gene therapy
Transplantation of patient's autologous CD34+ cells transduced with lentiviral vector containing GP91PHOX gene

Primary Outcome Measures :
  1. Safety of the procedure as measured by the incidence of adverse events [ Time Frame: 24 months ]
  2. Restoration and stability over time of the NADPH functioning granulocytes assessed by a DHR test [ Time Frame: 12 months ]

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

Information from the National Library of Medicine

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Ages Eligible for Study:   6 Months and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01855685

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United Kingdom
University College London Hospital (UCLH)
London, United Kingdom, NW1 2PG
Great Ormond Street Hospital NHS Foundation Trust
London, United Kingdom
Sponsors and Collaborators
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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)
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Responsible Party: Genethon Identifier: NCT01855685    
Other Study ID Numbers: G1XCGD.01
First Posted: May 16, 2013    Key Record Dates
Last Update Posted: May 21, 2021
Last Verified: May 2021
Keywords provided by Genethon:
XCGD, lentivirus, cellular therapy
Additional relevant MeSH terms:
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Granulomatous Disease, Chronic
Lymphoproliferative Disorders
Lymphatic Diseases
Pathologic Processes
Phagocyte Bactericidal Dysfunction
Leukocyte Disorders
Hematologic Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Immunologic Deficiency Syndromes
Immune System Diseases