Gene Therapy for SCID-X1 Using a Self-inactivating (SIN) Gammaretroviral Vector
Trial Snapshot
- Phase
- Not Applicable
- Enrollment
- 1
- Locations
- 1
- Primary Endpoint
- Immunological reconstitution
Study Overview
Brief Summary
X-linked severe combined immunodeficiency (SCID-X1) is an inherited disorder that results in failure of development of the immune system in boys. This trial aims to treat SCID-X1 patients using gene therapy to replace the defective gene.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- — to 16 Years (Child)
- Sex
- Male
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •No HLA identical (A,B,C,DR,DQ) family donor and no HLA identical unrelated donor available within 3 months of diagnosis or patients whose underlying clinical problems and prognosis would be significantly compromised by chemotherapy conditioning (including persisting pneumonitis, protracted diarrhoea requiring parental nutrition, ongoing visceral viral infection (herpes viruses, HSV,VZV,CMV, EBV or adenovirus), systemic BCG infection, virus-induced lymphoproliferation.
- •Diagnosis of classical SCID-X1 based on immunophenotype (absent, or reduced numbers of non-functional T lymphocytes) and confirmed by DNA sequencing
- •Parental/guardian voluntary consent
- •Boys between the ages of 0 and 16
Exclusion Criteria
- Not provided
Arms & Interventions
Single infusion of autologous CD34+ cells
Intervention: Single infusion of autologous CD34+ cells transduced with the self-inactivating (SIN) gammaretroviral vector pSRS11.EFS.IL2RG.pre (Genetic)
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Incidence of adverse reactions(from consent until 5 years post-infusion of gene-modified cells)
- Molecular characterisation of gene transfer(until 5 years post-infusion of gene-modified cells)
- Normalisation of nutritional status, growth, and development(until 5 years post-infusion of gene-modified cells)