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Gene Therapy for X-linked Chronic Granulomatous Disease

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: NCT02757911
Recruitment Status : Active, not recruiting
First Posted : May 2, 2016
Last Update Posted : March 5, 2020
Information provided by (Responsible Party):

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.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : March 2016
Estimated Primary Completion Date : June 2024
Estimated Study Completion Date : June 2024

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 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.

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

Secondary Outcome Measures :
  1. 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.

  2. Percentage of transduced CD34+ haematopoietic cells infused and of blood cells over time [ Time Frame: 60 months ]
  3. 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   24 Months and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

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.

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): NCT02757911

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Hôpital Necker Enfants Malades
Paris, France, 75015
Sponsors and Collaborators
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Principal Investigator: Stéphane BLANCHE, MD, PHD Hôpital Necker-Enfants Malades

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Responsible Party: Genethon Identifier: NCT02757911    
Other Study ID Numbers: G1XCGD.02
First Posted: May 2, 2016    Key Record Dates
Last Update Posted: March 5, 2020
Last Verified: March 2020
Keywords provided by Genethon:
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