Gene Therapy for Wiskott-Aldrich Syndrome (WAS)

Overview

This is a phase I/II study to evaluate the safety and efficacy of Hematopoietic Stem Cell genetherapy for the Wiskott-Aldrich Syndrome.

Full Title of Study: “Phase I/II Clinical Trial of Haematopoietic Stem Cell Gene Therapy for the Wiskott-Aldrich Syndrome”

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: November 13, 2019

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.

Interventions

  • Genetic: Autologous CD34 positive cells transduced with a lentiviral vector containing human WAS gene
    • transplantation of patient’s autologous CD34+ cells transduced with lentiviral vector containing human WAS gene

Arms, Groups and Cohorts

  • Experimental: study treatment
    • autologous CD34 positive cells transduced with a lentiviral vector containing the human WAS gene

Clinical Trial Outcome Measures

Primary Measures

  • Improvement in the eczema status
    • Time Frame: 2 years
    • Improvement in the eczema status as compared with the baseline status at study entry on clinical evaluation
  • Reduction in the frequency and severity of infection episodes
    • Time Frame: 2 years
    • Reduction in the frequency and severity of infection episodes as compared with the baseline status and the patient’s historical data collected over the 2 years prior to study entry
  • Reduction in the frequency and severity of bruising and bleeding episodes
    • Time Frame: 2 years
    • Reduction in the frequency and severity of bruising and bleeding episodes as compared with the baseline status and the patient’s historical data collected over the 2 years prior to study entry
  • Reduction in the frequency and severity of autoimmune disorders
    • Time Frame: 2 years
    • Reduction in the frequency and severity of autoimmune disorders as compared with the baseline status at study entry
  • Reduction in the number of disease related days of hospitalization
    • Time Frame: 2 years
    • Reduction in the number of disease related days of hospitalization as compared with the patient’s historical data collected over the 2 years prior to study entry

Secondary Measures

  • Occurrence and type of adverse events
    • Time Frame: 2 years
    • Occurrence and type of adverse events reported during the course of the study
  • Change in medical conditions
    • Time Frame: 2 years
    • Assessment of weight, vital signs, ECG and laboratory exams during the course of the study
  • Safety of lentivirus gene transfer into Hematopoietic Stem Cells
    • Time Frame: 3, 6, 12, 24 months / 6, 12, 18, 24 months
    • Detection of replication competent lentivirus (RCL) and lentivirus integration sites analysis
  • Improvement of microthrombocytopenia
    • Time Frame: 3, 6, 12, 24 months
    • Improvement of microthrombocytopenia as compared with the baseline evaluation at study entry
  • Decrease in the number and volume of platelets transfusions
    • Time Frame: 2 years
    • Decrease in the number and volume of platelets transfusions as compared with patient’s historical data collected over the 2 years prior to study entry
  • Evidence of sustained engrafment of WASP-expressing transduced cells
    • Time Frame: 6 weeks, 1, 3, 6, 9, 12, 18 & 24 months
    • Quantification of vector copy numbers and detection of vector-derived WASP expression
  • Reconstitution of humoral and cell mediated immunity
    • Time Frame: 9, 12, 18 & 24 months
    • Reconstitution of humoral and cell mediated immunity as compared with the baseline evaluation at study entry

Participating in This Clinical Trial

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

Gender Eligibility: Male

Minimum Age: N/A

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

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

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.