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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: X-Linked Chronic Granulomatous Disease
• Intervention / Treatment: Genetic: X vivo gene therapy

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, NW1 2PG
    • University College London Hospital (UCLH)
  • London, United Kingdom
    • Great Ormond Street Hospital NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Open label; X vivo gene therapy	Genetic: X vivo gene therapy; Transplantation of patient's autologous CD34+ cells transduced with lentiviral vector containing GP91PHOX gene

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Genethon
• Investigators: Principal Investigator: 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)

Study record dates

Study Major Dates

• Study Start (Actual): June 24, 2013
• Primary Completion (Anticipated): September 1, 2032
• Study Completion (Anticipated): September 1, 2032

Study Registration Dates

• First Submitted: May 14, 2013
• First Submitted That Met QC Criteria: May 14, 2013
• First Posted (Estimate): May 16, 2013

Study Record Updates

• Last Update Posted (Actual): April 6, 2023
• Last Update Submitted That Met QC Criteria: April 5, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: XCGD, lentivirus, cellular therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Immunologic Deficiency Syndromes; Immune System Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Hematologic Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Leukocyte Disorders; Phagocyte Bactericidal Dysfunction; Granuloma; Granulomatous Disease, Chronic
• Other Study ID Numbers: G1XCGD.01