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

NCT ID: NCT01855685

Last Updated: 2023-04-06

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-24
• Study Completion Date: 2032-09-30

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.

Conditions

X-Linked Chronic Granulomatous Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Open label

X vivo gene therapy

Group Type: EXPERIMENTAL

X vivo gene therapy

Intervention Type: GENETIC

Transplantation of patient's autologous CD34+ cells transduced with lentiviral vector containing GP91PHOX gene

Interventions

X vivo gene therapy

Transplantation of patient's autologous CD34+ cells transduced with lentiviral vector containing GP91PHOX gene

Intervention Type: GENETIC

Eligibility 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

• Minimum Eligible Age: 6 Months
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Genethon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Adrian Thrasher, MD, PHD

Role: PRINCIPAL_INVESTIGATOR

Great Ormond Street Hospital NHS Foundation Trust - London - UK

Janine Reichenbach, MD

Role: PRINCIPAL_INVESTIGATOR

University Children's Hospital Zürich - Switzerland

Hubert Serve, MD, PHD

Role: PRINCIPAL_INVESTIGATOR

Department of Hematology/Oncology, University Hospital Frankfurt and Institute for Biomedical Research, Georg-Speyer-Haus, Frankfurt - Germany

Emma Morris, MD, PHD

Role: PRINCIPAL_INVESTIGATOR

Royal Free Hospital / University College London Hospital (UCLH)

Locations

University College London Hospital (UCLH)

London, , United Kingdom

Great Ormond Street Hospital NHS Foundation Trust

London, , United Kingdom

Countries

United Kingdom

Other Identifiers

G1XCGD.01

Identifier Type: -

Identifier Source: org_study_id