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.
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: 4 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
Exclusion criteria
Exclusion criteria: Parents, guardians, patients unwilling to return for follow up during the 3 years long term period
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The purpose of this study is to perfom a long term follow up over a 3 years period of patients enrolled in the two clinical centres (UK and France) of the phase 1/2 clinical trial of haematopoietic stem cell gene therapy for the Wiskott-Aldrich Syndrome and treated with autologous CD34+ cells transduced with the w1.6_hWASP_WPRE (VSVg) lentiviral vector.;Secondary Objective: No;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 3 years post gene therapy To evaluate the safety of the gene therapy procedure for gene transfer analysis at 3, 4 and 5 years post gene therapy: 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 3, 4 and 5 years post gene therapy 2- Primary efficacy endpoints To evaluate the clinical status of patients: weight, ECG, and complete clinical exam at 3, 4 and 5 years post gene therapy To evaluate the evolution of the key medical events related to the WAS at 3, 4 and 5 years post gene therapy: eczema status, infections, bleeding symptoms, autoimmune manifestations. To evaluate the haematological reconstitution of the patient at 3, 4 and 5 years post gene therapy: CBC including platelet count and size. To evaluate the reconstitution of cell mediated and humoral immunity of the patient at 3, 4 and 5 years post gene therapy: 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 (PHA, Candida, CD3 stimulation).;Timepoint(s) of evaluation of this end point: 3,4 and 5 years post IMP treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1 Secondary efficacy endpoint To evaluate the evolution of the need for associated treatments at 3, 4 and 5 years post gene therapy (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. 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: 3,4 and 5 years post IMP treatment | — |
Countries
France, United Kingdom
Contacts
Public ContactMarie-Laurence Gourlay-Chu
Genethon
Outcome results
None listed