E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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. |
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E.1.1.1 | Medical condition in easily understood language |
The Wiskott-Aldrich Sydrome (WAS) is a genetic disorder that affects boys. It is caused by errors in a gene that makes a part of the blood and immune system. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
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E.4 | Principal exclusion criteria |
Parents, guardians, patients unwilling to return for follow up during the 3 years long term period |
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E.5 End points |
E.5.1 | 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). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
3,4 and 5 years post IMP treatment |
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E.5.2 | 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) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
3,4 and 5 years post IMP treatment |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 0 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |