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

This study is currently recruiting participants.
Verified March 2012 by Great Ormond Street Hospital for Children NHS Foundation Trust
Sponsor:
Information provided by:
Great Ormond Street Hospital for Children NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT01175239
First received: July 29, 2010
Last updated: March 1, 2012
Last verified: March 2012
History of Changes
  Purpose

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.


Condition Intervention Phase
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 Type: Interventional
Study Design: Allocation: Non-Randomized
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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Great Ormond Street Hospital for Children NHS Foundation Trust:

Primary Outcome Measures:
  • Immunological reconstitution [ Time Frame: 1-18 months post-infusion,then annually ] [ Designated as safety issue: No ]
    • 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 Outcome Measures:
  • Incidence of adverse reactions [ Time Frame: from consent until 5 years post-infusion of gene-modified cells ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Normalisation of nutritional status, growth, and development will be assessed at each follow-up visit by the investigator through clinical examinations.


Estimated Enrollment: 10
Study Start Date: April 2011
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   up to 16 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01175239

Contacts
Contact: Adrian Thrasher, Professor a.thrasher@ich.ucl.ac.uk

Locations
United Kingdom
Great Ormond Street Hospital for Children NHS Trust Recruiting
London, United Kingdom, WC1N 3JH
Principal Investigator: Adrian Thrasher, Professor            
Sponsors and Collaborators
Great Ormond Street Hospital for Children NHS Foundation Trust
  More Information

Publications:

Responsible Party: Biren Patel, Great Ormond Street Hospital for Children NHS Trust
ClinicalTrials.gov Identifier: NCT01175239     History of Changes
Other Study ID Numbers: 06MI10
Study First Received: July 29, 2010
Last Updated: March 1, 2012
Health Authority: United Kingdom: Research Ethics Committee
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Great Ormond Street Hospital for Children NHS Foundation Trust:
X-linked severe combined immunodeficiency, gene therapy
Patients will be enrolled following diagnosis and referral to Great Ormond Street Immunology Service.

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Severe Combined Immunodeficiency
X-Linked Combined Immunodeficiency Diseases
Immune System Diseases
Infant, Newborn, Diseases
 DNA Repair-Deficiency Disorders
Metabolic Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn

ClinicalTrials.gov processed this record on May 22, 2013