Gene Therapy for X-CGD

Disease Information

Descriptive Information
Brief Title † Gene Therapy for X-CGD
Official Title † A Phase I/II Gene Therapy Trial for X-CGD With a SIN Gammaretroviral Vector
Brief Summary X-linked chronic granulomatous disease (X-CGD) is a rare inherited immune defect, which is caused by the inability of phagocytic cells to produce reactive oxygen species due to a defect in the gp91phox subunit of the NADPH oxidase complex. X-CGD patients suffer from recurrent and life-threatening infections and severe hyperinflammatory complications. The only curative treatment for X-CGD is allogenic hematopoietic stem cell transplantation, but this procedure implies severe risks and many patients lack an appropriate donor. Therefore alternative curative approaches are urgently needed. In this study, patients will be treated with gene-corrected autologous CD34+ cells, using a SIN gammaretroviral vector for ex-vivo gene-therapy.
Detailed Description
Study Phase Phase 1/Phase 2
Study Type † Interventional
Study Design † Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary Outcome Measure † Transduction rate of granulocyte colony-stimulating factor (G-CSF) mobilized peripheral CD34+ cells from CGD patients with a SIN gamma retroviral vector
Secondary Outcome Measure † Frequency of infections as indicator for the clinical benefit for the patients
Condition † X-linked Chronic Granulomatous Disease
Intervention † Geneticex-vivo gene-therapy
Study Arms / Comparison Groups ex-vivo gene-therapy transplantation of genetically modified autologous CD34+ cells
Publications *

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information
Recruitment Status † Genetic
Estimated Enrollment † 5
Start Date † July 2013
Completion Date December 2019
Primary Completion Date December 2013
Eligibility Criteria † Inclusion Criteria: - Verified diagnosis of the X-linked form of chronic granulomatous disease, with loss of gp91phox expression (Western Blot). Evidence of less than 5% of normal oxidase production in circulating neutrophil granulocytes as measured by dihydrorhodamine- (DHR-) and nitro blue tetrazolium- (NBT-) assay - History of severe chronic infections with life-threatening course or severe steroid- sensitive or steroid insensitive granulomatous disease, with necessity of inpatient treatment, without sustained improvement even under maximum conservative treatment measures - No Human Leukocyte Antigen (HLA) identical (10/10 match) sibling- or unrelated donor, or contraindications for allogenic stem cell transplantation in presence of a suitable donor. The lack of an HLA-identical (10/10 match) sibling- or unrelated donor has to be confirmed by an unsuccessful search in national and international donor registers for at leat 3 months - Normal organ-function: glomerular filtration rate (GFR) ≥ 60ml/min., Bilirubin ≤ 1.5-fold upper reference-level, normal parameters for liver enzymes and clotting (TPZ 75-100%, partial thromboplastin time (PTT) 30-38sec, Fibrinogen 200-400mg/dl), Leukocytes > 3 x 10^9/l, Granulocytes > 1.5 x 10^9/l, Thrombocytes >100 x 10^9/l - Contraception from start of G-CSF application until 1 year after retransfusion of the gene-corrected cells - No interferon-gamma injection within two weeks prior to hematopoietic stem cell mobilization - Karnofsky-Index > 70% - Signed informed consent Exclusion Criteria: - Patients with non-controlled acute infections - Severe cardiac or pulmonary malfunctions: ejection fraction II°, arrhythmia requiring therapy, forced expiratory volume at one second/vital capacity (FEV1/VC) 1.5-fold upper reference-level - HIV-, Hepatitis B- or C - infection - Contraindications for G-CSF administration, as autoimmune vasculitis. - Contraindications for stem cell apheresis, as low hemoglobin
Gender Both
Ages 18 Years - N/A
Accepts Healthy Volunteers No
Contacts †† Hubert Serve, Prof., MD, 0049/69/6301,
Location Countries † Germany
Administrative Information
NCT ID † NCT01906541
Organization ID X-CGD
Secondary IDs ††
Responsible Party Sponsor-Investigator
Study Sponsor † Hubert Serve, Prof., MD
Collaborators ††
Investigators † : ,
Information Provided By
Verification Date August 2013
First Received Date † July 15, 2013
Last Updated Date August 1, 2013
† Required WHO trial registration data element.
†† WHO trial registration data element that is required only if it exists.
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