Wiskott-Aldrich syndrome (WAS) is a rare X-linked immunodeficiency caused by mutations in a single gene ,the Wiskott-Aldrich Syndrome Protein (WASP). WAS is characterised by micro-thrombocytopenia, recurrent infections,eczema and associated with a high incidence of auto-immunity and of lymphoid malignancies. Over 150 unique mutations in the WAS gene have been identified.Loss-of-function mutations in this gene have widespread consequences on hematopoietic lineages. MedDRA version: 19.1 Le
Conditions
Sponsors
Genethon
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Patients enrolled in the phase I/II and treated by a single infusion of autologous CD34+ cells transduced with the w1.6_hWASP_WPRE (VSVg) lentiviral vector for WAS conducted in France and United Kingdom (GTG 002.07 and GTG 003. 08) 2. Parents, guardians or patient signed informed consent Are the trial subjects under 18? yes Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 1 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1. Parents, guardians, patients unwilling to return for follow up during the 3 years long term period
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): 1.Primary safety endpoints To evaluate the incidence and type of SAEs and more specifically the incidence and nature of delayed events such as malignancies, hematologic, autoimmune events, mortality continuously over the 8 years duration of the post gene therapy follow-up To evaluate the safety of the gene therapy procedure for gene transfer analysis at yearly gene therapy visits: lentiviral integration sites in different cell subpopulation, quantification of VCN (vector copy numbers) on sorted cell population by real time by q-PCR To evaluate the safety of the gene therapy procedure for replication competent lentivirus (RCL) at yearly post gene therapy visits. 2.Primary efficacy endpoints To evaluate the clinical status of patients: weight, and complete clinical exam at yearly post gene therapy visits. For ECG, assessment will be done at 3, 4 and 5 years post gene therapy. To evaluate the evolution of the key medical events related to the WAS at yearly post gene therapy visits: eczema status, infections, bleeding symptoms, autoimmune manifestations. To evaluate the haematological reconstitution of the patient at yearly post gene therapy visits: CBC including platelet count and size. To evaluate the reconstitution of cell mediatd and humoral immunity of the patient at yearly post gene therapy visits: Immunophenotyping panel (Lymphocytes subset including Wasp protein expression), Restoration of antibody production (IgA, IgM, IgG, IgE). Whole blood lymphocytes proliferation assays - humoral response to antigen (CD3 stimulation). Humoral response to antigen (PHA, Candida) will be assessed at 3, 4 and 5 years post gene therapy.;Timepoint(s) of evaluation of this end point: yearly visits until 8 years post gene therapy;Main Objective: Long term follow up of WAS patients who received an autologous transplantation with CD34+ cells transduced with the w1.6_hWASP_WPRE (VSVg) lentiviral vector.;Secondary Objective: | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.Secondary efficacy endpoint To evaluate the evolution of the need for associated treatments at yearly post gene therapy visits (Immunoglobulins, antibacterial, antifungal and antiviral drugs, transfusions). To evaluate the representation of TCR families by PCR, TREC (TCR excision circle) and TCR V beta panel at 3, 4 and 5 years post gene therapy. 2.Secondary safety endpoint (optional) To evaluate the bone marrow integrity at 3, 4 and 5 years post gene therapy by performing a bone marrow aspiration (optional) ;Timepoint(s) of evaluation of this end point: yearly visits until 8 years post gene therapy | — |
Countries
United Kingdom
Contacts
Public ContactGeraldine Honnet
Genethon
Outcome results
None listed