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Trial record 7 of 26 for:    Recruiting, Not yet recruiting, Available Studies | "Granulomatous Disease, Chronic"

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

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ClinicalTrials.gov Identifier: NCT01855685
Recruitment Status : Recruiting
First Posted : May 16, 2013
Last Update Posted : May 21, 2018
Sponsor:
Information provided by (Responsible Party):
Genethon

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

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 5 participants
Allocation: Non-Randomized
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
Study Start Date : February 2013
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : March 2020


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 ]


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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
Criteria

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 ClinicalTrials.gov identifier (NCT number): NCT01855685


Locations
Germany
University Hospital Frankfurt and Institute for Biomedical Research, Georg-Speyer-Haus Withdrawn
Frankfurt, Germany
Switzerland
University Children's Hospital Zürich Withdrawn
Zurich, Switzerland, CH-8032
United Kingdom
University College London Hospital (UCLH) Recruiting
London, United Kingdom, NW1 2PG
Contact: Emma Morris    +44 (0)20 7794 0500    e.morris@ucl.ac.uk   
Royal Free Hospital (RFH) Recruiting
London, United Kingdom, NW3 2QG
Contact: Emma Morris    +44(0) 207 794 05 00    e.morris@ucl.ac.uk   
Great Ormond Street Hospital NHS Foundation Trust Recruiting
London, United Kingdom
Contact: Adrian THRASHER, MD, Phd    + 44 (0)2079052292    A.Thrasher@ich.ucl.ac.uk   
Sponsors and Collaborators
Genethon
Investigators
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)

Responsible Party: Genethon
ClinicalTrials.gov Identifier: NCT01855685     History of Changes
Other Study ID Numbers: G1XCGD.01
First Posted: May 16, 2013    Key Record Dates
Last Update Posted: May 21, 2018
Last Verified: May 2018

Keywords provided by Genethon:
XCGD, lentivirus, cellular therapy

Additional relevant MeSH terms:
Granulomatous Disease, Chronic
Granuloma
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