Phase 1/2 clinical trial of haematopoietic stem cell gene therapy for the Wiskott-Aldrich Syndrome. An open labelled, non-randomised, phase I/II, cohort study involving a single infusion of autologous CD34+ cells transduced with the lentiviral vector w1.6_hWASP_WPRE (VSVg) in up to 5 patients with WAS.
Conditions
Interventions
Product Name: Autologous CD34+ cells transduced with the Lentiviral vector containing the human Wiskott Aldrich Sy
Product Code: GTG003.08
Pharmaceutical Form: Solution for injection
Sponsors
GENETHON
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. a. Males of all ages b. Severe WAS (clinical score 3 – 5) or absence of WAS protein in peripheral blood mononuclear cells determined by Western blotting and flow cytometry c. Molecular confirmation by WAS gene DNA sequencing 2. Unless desease severity indicates that one cannot wait for 3 months (score 5; refractory thrombocytopenia with platelets =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. a. Patient with HLA-genotypically identical bone marrow b. Patient with 10/10 or 9/10 antigen HLA-matched unrelated donor or with HLA-matched cord blood 2. a. Contraindication to leukapheresis i. Anaemia (Hb < 8g/dl) ii.Severe vascularitis iii.Refractory thrompopenia b. Contraindication to bone marrow harvest c. Contraindication to administration of conditioning medication 3. HIV seropositive patient
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: To improve the overall health of the patient, including reduction in frequency of infections, resolution of autoimmunity, and improvement in eczema, reduction in bruising and bleeding episodes. To evaluate the longitudinal clinical effect in terms of improved immunity. ;Primary end point(s): 1. Safety of conditioning regimen (hematopoietic recovery within 6 weeks a assessed by absolute neutrophil count (ANC) above 0.5 x 109 /l) 2. Safety of the transduction procedure (as assessed by availability of greater than 1 x 106CD34+ cells per kg; retrospective undetectable RCL; and cell viability equal to or greater than 70%, in accordance with the GMO release criteria). 3. Engraftment of genetically corrected haematopoietic progenitors and/or differentiated cells in peripheral blood and/or in bone marrow (as assessed by evidence of vector sequences or transgene expression in the cells) 4. Reconstitution of cell mediated and humoral immunity (as assessed by evidence of changes in T cell function and circulating immunoglobulin levels). 5. Correction of microthrombocytopenia (as assessed by increased blood platelet counts, expected to rise above 50,000/mm3 and platelets size restoration) ;Main Objective: To safely administer a lentiviral gene therapy vector encoding the human WAS cDNA in patients with WAS To provide sustained engraftment of WASP-expressing transduced cells, reconstitution of humoral and cell mediated immunity, and correction of microthrombocytopenia. | — |
Countries
France
Outcome results
None listed