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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10047992 |
E.1.2 | Term | Wiskott-Aldrich syndrome |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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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 |
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. |
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E.2.2 | Secondary objectives of the trial | |
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 |
1. 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 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. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
yearly visits until 8 years post gene therapy |
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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 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)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
yearly visits until 8 years post gene therapy |
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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 | No |
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.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
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 | 8 |
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 | 8 |