Gene Therapy for X-linked Severe Combined Immunodeficiency (SCID-X1)
|X-linked Severe Combined Immunodeficiency||Genetic: Single infusion of autologous CD34+ cells transduced with the self-inactivating (SIN) gammaretroviral vector pSRS11.EFS.IL2RG.pre||Phase 1 Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Gene Therapy for SCID-X1 Using a Self-inactivating (SIN) Gammaretroviral Vector|
- Immunological reconstitution [ Time Frame: 1-18 months post-infusion,then annually ]
- Immunophenotyping: detection of naïve CD3+ T-cell numbers, CD4, CD8, TCRαβ, TCRγδ, CD16+CD56+ NK & gamma chain expression. TRECs may be enumerated as surrogate marker for new thymic emigrants post-gene therapy
- Lymphocyte proliferation assays to test function of T cells
- Representation of TCR families by flow cytometry (Vβ phenotyping), & CDR3 PCR spectratyping (Vβ spectratyping) to monitor physiological & potentially pathological clonal expansions
- Restoration of antibody production (IgA, IgM, IgG) & serological responses to vaccinations & natural infections.
- Incidence of adverse reactions [ Time Frame: from consent until 5 years post-infusion of gene-modified cells ]
At each scheduled visit, adverse events that might have occurred since the previous visit or assessment will be elicited from the patient/parent/guardian.
The investigators will maintain a record of all adverse events/occurrences in patients participating in the clinical trial. This record will be noted in the patient's medical notes.
Adverse events that have a causal relationship to the IMP (ARs) and SAEs will be recorded on the AE reporting section of the CRF.
- Molecular characterisation of gene transfer [ Time Frame: until 5 years post-infusion of gene-modified cells ]Quantification of transgene copy numbers is determined on sorted cell populations by real-time PCR methodology. Detailed integration analysis may be used to investigate specific clonal expansions.
- Normalisation of nutritional status, growth, and development [ Time Frame: until 5 years post-infusion of gene-modified cells ]Normalisation of nutritional status, growth, and development will be assessed at each follow-up visit by the investigator through clinical examinations.
|Study Start Date:||April 2011|
|Estimated Primary Completion Date:||December 2018 (Final data collection date for primary outcome measure)|
|Experimental: Single infusion of autologous CD34+ cells||
Genetic: Single infusion of autologous CD34+ cells transduced with the self-inactivating (SIN) gammaretroviral vector pSRS11.EFS.IL2RG.pre
Single infusion of autologous CD34+ cells transduced with the self-inactivating (SIN) gammaretroviral vector pSRS11.EFS.IL2RG.pre
Please refer to this study by its ClinicalTrials.gov identifier: NCT01175239
|Great Ormond Street Hospital for Children NHS Trust|
|London, United Kingdom, WC1N 3JH|