Clinical Trial: Gene Therapy for X-linked Chronic Granulomatous Disease

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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

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.


Detailed Summary:
Sponsor: Genethon

Current Primary Outcome:

  • Safety as measured by the incidence of adverse events [ Time Frame: 24 months ]
  • Restoration and stability over time of the NADPH functioning granulocytes assessed by a Dihydrorhodamine (DHR) flow cytometry test [ Time Frame: 12 months ]


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Clinical improvement [ Time Frame: 24 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.
  • Percentage of transduced CD34+ haematopoietic cells infused and of blood cells over time [ Time Frame: 24 months ]
  • Immunological reconstitution [ Time Frame: 24 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.


Original Secondary Outcome: Same as current

Information By: Genethon

Dates:
Date Received: April 20, 2016
Date Started: March 2016
Date Completion: December 2019
Last Updated: April 27, 2016
Last Verified: April 2016