Text Size

Gene Therapy for Wiskott-Aldrich Syndrome (WAS)

This study is currently recruiting participants.
Verified May 2011 by Genethon
Sponsor:
Collaborators:
Great Ormond Street Hospital for Children NHS Foundation Trust
Institute of Child Health
Information provided by:
Genethon
ClinicalTrials.gov Identifier:
NCT01347242
First received: May 3, 2011
Last updated: NA
Last verified: May 2011
History: No changes posted
  Purpose

This clinical trial is an ex vivo gene therapy trial. It consists in the correction of the genetic mutation harbored by patients with Wiskott-Aldrich Syndrome, through patients' own haematopoietic stem cells transplantation after modification with a lentiviral vector expressing the human Wiskott-Aldrich Syndrome protein gene.


Condition Intervention Phase
Wiskott-Aldrich Syndrome
 Biological: ex vivo gene therapy
 Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Clinical Trial of Haematopoietic Stem Cell Gene Therapy for the Wiskott-Aldrich Syndrome

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Genethon:

Primary Outcome Measures:
  • number of patients safely receiving the conditioning regimen [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
    safety of conditioning regimen is measured by hematopoietic recovery within 6 weeks.

  • number of patients whose stem cells are safely transduced [ Time Frame: 1 week ] [ Designated as safety issue: Yes ]

    safety of transduction procedure is determined prior to transplantation and is assessed through:

    • transduced cells number determination
    • cell viability measure
    • RCL detection

  • number of patients with engraftment of genetically corrected hematopoietic progenitors/differentiated cells [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    engraftment is assessed by evidence of vector sequences or transgene expression in the cells.

  • number of patients with reconstituted cell mediated and humoral immunity [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    reconstitution of cell mediated and humoral immunity is assessed by evidence of changes in T cell function and circulating immunoglobulin levels

  • number of patients with corrected microthrombocytopenia [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    correction of microthrombocytopenia is assessed by blood platelet counts, expected to rise above 50,000/mm3


Secondary Outcome Measures:
  • number of patients with reduced frequency of infection [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    reduction in frequency of infection is evaluated by clinical histroy, complete physical examinations, heamatological and microbiological tests

  • number of patients with resolution/reduction of autoimmunity [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    resolution/reduction of autoimmunity is considered as a decrease from baseline observations assessed by clinical examination

  • number of patients with improvement in eczema [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    improvement of eczema is considered as a decrease from baseline observations assessed by clinical examinations

  • number of patients with reduction in bruising and bleeding episodes [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    reduction in bruising and bleeding episodes is assessed by clinical monitoring


Estimated Enrollment: 5
Study Start Date: March 2011
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: ex vivo gene therapy
    transplantation of patient's autologous CD34+ cells transduced with lentiviral vector containing human WASP gene
Detailed Description:

This clinical trial is an ex vivo gene therapy trial. the investigational product corresponds to autologous CD34+ cells transduced with a lentiviral vector harboring the human WASP gene.

  Eligibility

Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • males of all ages
  • severe WAS (clinical score 3-5) or absence of WAS protein in peripheral blood mononuclear cells determined by Western blotting and flow cytometry
  • molecular confirmation by WAS gene DNA sequencing
  • lack of HLA-genotypically identical bone marrow or of a 10/10 antigen HLA-matched unrelated donor or cord blood after 3 month search
  • parental, guardian, patient signed informed consent/assent
  • willing to return for follow-up
  • only for patients who have received previous allogenic hematopoietic stem cell transplant:
  • failed allogenic hematopoietic stem cell transplant
  • contraindication to repeat transplantation

Exclusion Criteria:

  • patient with HLA-genotypically identical bone marrow
  • patient with 10/10 antigen HLA-matched unrelated donor or cord blood
  • contraindication to leukapheresis
  • contraindication to bone marrow harvest
  • contraindication to administration of conditioning medication
  • HIV positive patient
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01347242

Locations
United Kingdom
Great Ormond Street Hospital Recruiting
London, United Kingdom, WC1N 1EH
Contact: Adrian Thrasher, MD, PHD         a.thrasher@ich.ucl.ac.uk    
Principal Investigator: Adrian Thrasher, MD, PHD            
Sponsors and Collaborators
Genethon
Great Ormond Street Hospital for Children NHS Foundation Trust
Institute of Child Health
  More Information

No publications provided

Responsible Party: Adrian Thrasher, Institute of Child Health
ClinicalTrials.gov Identifier: NCT01347242     History of Changes
Other Study ID Numbers: GTG002.07
Study First Received: May 3, 2011
Last Updated: May 3, 2011
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Genethon:
Wiskott-Aldrich Syndrome
Primary immune deficiency
ex vivo gene therapy
hematopoietic stem cells

Additional relevant MeSH terms:
Wiskott-Aldrich Syndrome
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphopenia
 Leukopenia
Leukocyte Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Immunologic Deficiency Syndromes
Immune System Diseases

ClinicalTrials.gov processed this record on May 22, 2013