Gene Therapy for X-linked Severe Combined Immunodeficiency (SCID-X1)

Great Ormond Street Hospital for Children NHS Foundation Trust1 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

X-linked Severe Combined Immunodeficiency

Interventions

Single infusion of autologous CD34+ cells transduced with the self-inactivating (SIN) gammaretroviral vector pSRS11.EFS.IL2RG.preGENETIC

Single infusion of autologous CD34+ cells transduced with the self-inactivating (SIN) gammaretroviral vector pSRS11.EFS.IL2RG.pre

Eligibility

Sex: MALEMax age: 16 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. 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. 2. Diagnosis of classical SCID-X1 based on immunophenotype (absent, or reduced numbers of non-functional T lymphocytes) and confirmed by DNA sequencing 3. Parental/guardian voluntary consent 4. Boys between the ages of 0 and 16

Locations (1)

Great Ormond Street Hospital for Children NHS Trust

London, United Kingdom

Outcomes

Primary Outcomes

Immunological reconstitution

* 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.

Time frame: 1-18 months post-infusion,then annually

Secondary Outcomes

Incidence of adverse reactions

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.

Time frame: from consent until 5 years post-infusion of gene-modified cells

Molecular characterisation of gene transfer

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.

Time frame: until 5 years post-infusion of gene-modified cells

Normalisation of nutritional status, growth, and development

Normalisation of nutritional status, growth, and development will be assessed at each follow-up visit by the investigator through clinical examinations.

Time frame: until 5 years post-infusion of gene-modified cells

Data from ClinicalTrials.gov

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