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

NCT01855685 | Terminated Phase 1

• 1 other identifier: G1XCGD.01
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 2

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

Keywords

XCGD, lentivirus, cellular therapy

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• Normalisation of nutritional status, growth, development, severe infection and/or inflammatory complication which recommended patient's inclusion

  24 months

• Percentage of transduced CD34+ haematopoietic cells infused and of blood cells over time

  24 months

• Immunological reconstitution

  24 months

Study Arms (1)

Open label

EXPERIMENTAL

X vivo gene therapy

Genetic: X vivo gene therapy

Interventions

X vivo gene therapy GENETIC

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

Open label

Eligibility Criteria

• Age: 6 Months+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Contraindication for leukapheresis
• Contraindication for administration of conditioning medication
• Administration of gammainterferon within 30 days before the infusion of transduced autologous CD34+ cells

Sponsors & Collaborators

• Genethon: lead

Study Sites (2)

University College London Hospital (UCLH)

London, NW1 2PG, United Kingdom

Location

Great Ormond Street Hospital NHS Foundation Trust

London, United Kingdom

Location

MeSH Terms

Conditions

Granulomatous Disease, Chronic

Condition Hierarchy (Ancestors)

Phagocyte Bactericidal Dysfunction; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunologic Deficiency Syndromes; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• 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)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2013
• First Posted: May 16, 2013
• Study Start: June 24, 2013
• Primary Completion: June 4, 2021
• Study Completion: October 17, 2025
• Last Updated: April 13, 2026

Record last verified: 2025-10

Locations

GB (2)