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


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.

Full Title of Study: “Gene Therapy for SCID-X1 Using a Self-inactivating (SIN) Gammaretroviral Vector”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: December 2018


  • 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

Arms, Groups and Cohorts

  • Experimental: Single infusion of autologous CD34+ cells

Clinical Trial Outcome Measures

Primary Measures

  • 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 Measures

  • 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.

Participating in This Clinical Trial

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

Gender Eligibility: Male

Minimum Age: N/A

Maximum Age: 16 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Great Ormond Street Hospital for Children NHS Foundation Trust
  • Provider of Information About this Clinical Study
    • Sponsor


Thornhill SI, Schambach A, Howe SJ, Ulaganathan M, Grassman E, Williams D, Schiedlmeier B, Sebire NJ, Gaspar HB, Kinnon C, Baum C, Thrasher AJ. Self-inactivating gammaretroviral vectors for gene therapy of X-linked severe combined immunodeficiency. Mol Ther. 2008 Mar;16(3):590-8. doi: 10.1038/ Epub 2008 Jan 8.

Cavazzana-Calvo M, Hacein-Bey S, de Saint Basile G, Gross F, Yvon E, Nusbaum P, Selz F, Hue C, Certain S, Casanova JL, Bousso P, Deist FL, Fischer A. Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease. Science. 2000 Apr 28;288(5466):669-72.

Hacein-Bey-Abina S, Le Deist F, Carlier F, Bouneaud C, Hue C, De Villartay JP, Thrasher AJ, Wulffraat N, Sorensen R, Dupuis-Girod S, Fischer A, Davies EG, Kuis W, Leiva L, Cavazzana-Calvo M. Sustained correction of X-linked severe combined immunodeficiency by ex vivo gene therapy. N Engl J Med. 2002 Apr 18;346(16):1185-93.

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