E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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.
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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 |
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.
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E.2.2 | Secondary objectives of the trial |
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.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 <5000 with bleeding or severe autoimmunity), a. Lack of HLA-genotypically identical bone marrow after 3 month search b. Lack of a 10/10 or 9/10 antigen HLA-matched unrelated donor after 3 month search c. Lack of a HLA-matched cord blood after 3 month search
3. Parental, guardian, patient signed informed consent/assessment
4. Willing to return for follow-up during the 2 year study and lifelong for off study review
5. Only for patients who have received previous allogenic haematopoietic stem cell transplant: a. Failed allogenic haematopoietic stem cell transplant b. Contraindication to repeat allogenic transplantation
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E.4 | Principal 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
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E.5 End points |
E.5.1 | 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)
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
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) | Yes |
E.7.1.1 | First administration to humans | Yes |
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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 1 |
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 | Information not present in EudraCT |
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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The end of the study is the 2 year follow-up for the last patient. There is an open follow-up of the patient for all the life of the patient.
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |