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

X-Linked Chronic Granulomatous Disease Clinical Trial

— CGD  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01855685
• Other study ID #: G1XCGD.01
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: June 24, 2013
• Est. completion date: September 2032

Study information

• Verified date: April 2023
• Source: Genethon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 3
• Est. completion date: September 2032
• Est. primary completion date: September 2032
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 6 Months and older

Eligibility

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

Related Conditions & MeSH terms

• Granuloma
• Granulomatous Disease, Chronic
• X-Linked Chronic Granulomatous Disease

Intervention

Genetic:
• X vivo gene therapy
Transplantation of patient's autologous CD34+ cells transduced with lentiviral vector containing GP91PHOX gene

Locations

Country	Name	City	State
United Kingdom	Great Ormond Street Hospital NHS Foundation Trust	London
United Kingdom	University College London Hospital (UCLH)	London

Sponsors (1)

Lead Sponsor	Collaborator
Genethon

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety of the procedure as measured by the incidence of adverse events		24 months
Primary	Restoration and stability over time of the NADPH functioning granulocytes assessed by a DHR test		12 months
Secondary	Normalisation of nutritional status, growth, development, severe infection and/or inflammatory complication which recommended patient's inclusion		24 months
Secondary	Percentage of transduced CD34+ haematopoietic cells infused and of blood cells over time		24 months
Secondary	Immunological reconstitution		24 months