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

Phase 1

Active, not recruiting

• Conditions: X-Linked Chronic Granulomatous Disease
• Interventions: Genetic: X vivo gene therapy

• Registration Number: NCT01855685
• Lead Sponsor: 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-05-14
• Study First Submitted QC: 2013-05-14
• Study First Posted: 2013-05-16
• Study Start: 2013-06-24
• Status Verified: 2023-04
• Last Update Submitted: 2023-04-05
• Last Update Posted: 2023-04-06
• Primary Completion: 2032-09
• Study Completion: 2032-09

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Male
• Target Recruitment: 3

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Open label	X vivo gene therapy	X vivo gene therapy

Primary Outcome Measures

Name	Time	Method
Safety of the procedure as measured by the incidence of adverse events	24 months
Restoration and stability over time of the NADPH functioning granulocytes assessed by a DHR test	12 months

Secondary Outcome Measures

Name	Time	Method
Percentage of transduced CD34+ haematopoietic cells infused and of blood cells over time	24 months
Immunological reconstitution	24 months
Normalisation of nutritional status, growth, development, severe infection and/or inflammatory complication which recommended patient's inclusion	24 months

Trial Locations

Locations (2)

University College London Hospital (UCLH); 🇬🇧 London, United Kingdom

Great Ormond Street Hospital NHS Foundation Trust; 🇬🇧 London, United Kingdom