E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acquired severe aplastic anaemia and transfusion dependent non-severe aplastic anaemia |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10002969 |
E.1.2 | Term | Aplastic anemia |
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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 |
To assess the tolerability and efficacy of rabbit antithymocyte globulin (ATG, Thymoglobuline®) with ciclosporin (CSA) in the first line treatment of patients with acquired severe aplastic anaemia (SAA), and patients with non-severe aplastic anaemia (NSAA) and who are transfusion dependent. |
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E.2.2 | Secondary objectives of the trial |
To compare the response rate of the combination of rabbit ATG (Thymoglobuline® and CSA from this pilot study with the response rate observed in a series of matched AA patients; treated after 1994 with the combination of horse ATG (Lymphoglobuline®) and CSA; obtained from the EBMT database (comparative study). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) To define aplastic anaemia there must be at least two of the following: (1) haemoglobin < 10g/dl; (2) platelet count < 50 x 109/l; (3) neutrophil count < 1.5 x 109/l, and a hypocellular bone marrow on bone marrow biopsy 1.1) SAA as defined by a hypocellular bone marrow of <25% cellularity and 2 of the following 3 peripheral blood criteria: neutrophil count < 0.5 x 109/l, platelets < 20 x 109/l and/or reticulocytes < 20 x 109/l 1.2) NSAA as defined by a hypocellular bone marrow and cytopenia in at least two cell lines AND neutrophil count > 0.5 x 109/l, and red cell and/or platelet transfusion dependence 1.3) Acquired AA 2) Time from diagnosis to study registration ≤ 6mths 3) No prior treatment except for haemopoietic growth factors given for no more than 4 weeks, or prior treatment with androgens. 4) Age ≥ 16yrs (≥ 18yrs in Germany and Switzerland), with no upper age limit.
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E.4 | Principal exclusion criteria |
1) Eligibility for an HLA-matched sibling donor transplant for SAA patients 2) Prior therapy with ATG or CSA 3) Haematopoeitic growth factors more than 4 weeks before study enrollment 4) Diagnosis of Fanconi anaemia, dyskeratosis congenita or congenital bone mar¬row failure syndrome 5) Evidence of myelodysplastic disease 6) Paroxysmal nocturnal haemoglobinuria with evidence of significant haemolysis, history of PNH associated thrombosis or a PNH clone > 50% by flow cytometry 7) Diagnosis or previous history of carcinoma (except local cervical, basal cell, squamous cells, or melanoma) 8) Subject is pregnant (e.g. positive HCG test) or is breast feeding 9) Severe uncontrolled infection or unexplained fever > 38oC 10) Subjects who have hepatic, renal cardiac, metabolic or other concur¬rent diseases of such severity that life expectancy is less than 3 months |
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E.5 End points |
E.5.1 | Primary end point(s) |
Response at 6 months post treatment To compare the response rate of the combination of rabbit ATG (Thymoglobuline® and CSA from this pilot study with the response rate observed in a series of matched AA patients; treated after 1994 with the combination of horse ATG (Lymphoglobuline®) and CSA; obtained from the EBMT database (comparative study). |
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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 | No |
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) | 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 | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Historical cases, patients who received horse ATG (Lymphoglobulin®) |
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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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 19 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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End of trial is when last patient has completed last visit (2 year follow-up visit) |
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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 | 6 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |