- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01855685
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
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
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
Accepts Healthy Volunteers
Genders Eligible for Study
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)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Open label
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
Time Frame: 24 months
|
24 months
|
Restoration and stability over time of the NADPH functioning granulocytes assessed by a DHR test
Time Frame: 12 months
|
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
Time Frame: 24 months
|
24 months
|
Percentage of transduced CD34+ haematopoietic cells infused and of blood cells over time
Time Frame: 24 months
|
24 months
|
Immunological reconstitution
Time Frame: 24 months
|
24 months
|
Collaborators and Investigators
Sponsor
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)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- G1XCGD.01
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact [email protected]. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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