E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Immune Thrombocytopenic Purpura (ITP) in RhD positive, non-splenectomized adult subjects. Púrpura trombocitopénica inmune (PTI) en pacientes adultos no esplenectomizados y RhD positivos |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the safety of Sym001 following a single intravenous dose, at multiple dose levels in the treatment of ITP in RhD positive, non-splenectomized adult subjects.
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of Sym001 following a single intravenous dose in the treatment of ITP in RhD positive, non-splenectomized adult subjects.
To evaluate the binding of Sym001 to RBCs following a single intravenous dose of Sym001 in the treatment of ITP in RhD positive, non-splenectomized adult subjects.
To evaluate an appropriate dose range of Sym001 for Phase 3.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Informed consent obtained before any trial-related procedures. 2. Age 18-75 inclusive. 3. Confirmed presence of thrombocytopenia with platelet count < 30,000/mm3 at the pre-dose visit. In each cohort a maximum of 3 subjects will be included with platelet counts < 10,000/mm3, in order to limit variability. The average of 2 individual pre-dose platelet counts taken on the dosing day and within > 1 hour interval between each other and both being < 30,000/mm3 will be used to confirm thrombocytopenia. 4. History of isolated ITP (thrombocytopenia with no known aetiology, blood smear showing normal appearing platelets or, if performed, a bone marrow showing adequate megacariocytosis and normal erythroid and myeloid morphology). 5. RhD-positive serology. 6. Previous treatment and response to first line therapy for ITP (corticosteroids, anti-D or IVIg), with response being defined as an increase in platelet count to ≥ 50,000/mm3. 7. female and of child-bearing potential, subject has a negative pregnancy test at screening. 8. If subject is a female of child-bearing potential, subject agrees to use a medically accepted form of contraception from the time of enrolment to completion of all follow-up trial visits.
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E.4 | Principal exclusion criteria |
1. Known clinical picture suggestive of other causes of thrombocytopenia, especially systemic lupus erythematosus, antiphospholipid syndrome, Evans syndrome, immunodeficiency states, lymphoproliferative disorders, liver disease, ingestion of drugs such as quinidine/quinine, heparin and sulfonamides and hereditary thrombocytopenia confirmed by relevant laboratory findings. 2. Suspected infection with HIV, hepatitis C, H. pylori unless corresponding laboratory tests are negative. 3. Clinical splenomegaly (the spleen should not be palpable at more than 1 finger breadth below the costal margin). 4. History of abnormal bone marrow examination. 5. At pre-dose visit: bleeding risk requiring emergency treatment for ITP or an ongoing haemorrhage requiring medical intervention. 6. History of anaphylaxis or hypersensitivity reactions following IVIg or anti-D treatment. 7. History of immune haemolytic anaemia. 8. Underlying haemolytic condition (e.g. reticulocyte count > 3%). 9. Planned surgery during the trial period. 10. Haemoglobin pre-dose value lower than 2g/dL below the lower limit of the laboratory normal range for gender and age. 11. History of splenectomy. 12. Known malignancy (except basocellular carcinoma). 13. Received investigational agent within 90 days prior to enrolment. 14. Positive DAT (direct Coombs-test) at screening unless subject has received treatment with anti-D products within 3 months prior to screening with prior negative DAT. 15. Known non-responders to most recent anti-D treatment (despite any initial response to treatment). 16. Any other current treatment for ITP except corticosteroids at doses up to 20 mg/day. (Acceptable if the dose has been constant for 2 weeks or more before trial drug administration). 17. Therapy with IVIg, anti-D or any other treatment of ITP within 4 weeks prior to enrolment. 18. Therapy with alkylating agents or rituximab within 8 weeks prior to enrolment 19. Any antithrombotic treatment (except acetyl salicylic acid at doses up to 150 mg daily) within 7 days prior to pre-dosing visit or planned during the trial. 20. PT/INR and aPTT out of normal range at the pre-dose visit 21. History of thrombosis or known thrombophilia. 22. Diseases other than ITP that may influence the result of the trial as judged by the Investigator. 23. Creatinine, alanine aminotransferase (ALT), alkaline phosphatase (ALP), and Albumin 25% or more outside normal range value (according to the local laboratory) at pre-dose visit. 24. Current or planned treatment with erythropoietin. 25. Subject is pregnant, breast feeding or intends to become pregnant.
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E.5 End points |
E.5.1 | Primary end point(s) |
Incidence and severity of Adverse Events (AEs), including Serious Adverse Events (SAEs), Serious Drug Reactions (SDRs) and Adverse Events of Special Interest (AESIs) during the 6-week trial period.
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 | 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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 14 |
E.8.9.1 | In the Member State concerned days | 7 |
E.8.9.2 | In all countries concerned by the trial months | 14 |
E.8.9.2 | In all countries concerned by the trial days | 7 |