E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
low or intermediate-1 risk MDS |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028533 |
E.1.2 | Term | Myelodysplastic syndrome |
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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 evaluate the efficacy of romiplostim for the treatment of thrombocytopenia in subjects with international prognostic scoring system (IPSS) low or intermediate-1 risk MDS as measured by the number of clinically significant bleeding events. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the number of platelet transfusions To evaluate the overall number of bleeding events To evaluate the utilization of platelet transfusions To evaluate platelet hematologic improvement (HI-P), per MDS IWG 2006 guidelines To evaluate overall survival To evaluate patient-reported bleeding events |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Diagnosis of MDS using the WHO classification Per MDS IPSS, low or intermediate-1 risk MDS The mean of the two platelet counts taken within 4 weeks prior to randomization must be: o ≤ 20 x 109/L, with no individual count >30 x 109/L, with or without a history of bleeding, OR o ≤ 50 x 109/L, with no individual count >60 x 109/L with a history of bleeding. A standard of care platelet count taken prior to Informed Consent may be used as 1 of the 2 counts taken within 4 weeks prior to randomization Subjects must be ≥18 and ≤ 90 years of age at the time of informed consent. Subjects between 85 and 90 years of age must have been diagnosed with MDS ≤ 5 years from study start. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 Adequate liver function, as evidenced by a serum bilirubin ≤ 2 times the laboratory normal range and unconjugated bilirubin ≥ 90% of total bilirubin (except for patients with a confirmed diagnosis of Gilberts Disease), ALT ≤ 3 times the laboratory normal range, and AST ≤3 times the laboratory normal range A serum creatinine concentration ≤ 2 mg/dl (≤176.8 μmol/L) Bone marrow biopsy and aspirate with cytogenetics within 3 months of starting first dose of investigational product Written Informed Consent |
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E.4 | Principal exclusion criteria |
Have ever received any disease-modifying treatment for MDS Previously diagnosed with intermediate-2 or high risk MDS using the IPSS Prior history of leukemia, aplastic anemia, or other non-MDS related bone marrow stem cell disorder Prior history of hematopoietic stem cell transplantation Persistent peripheral blood monocytosis (≥ 3 months with an absolute monocyte count >1,000/μL) Prior malignancy (other than in situ cervical cancer, non-melanoma skin cancer, or in situ carcinoma) unless treated with curative intent and without evidence of disease for ≥ 3 years before randomization Active or uncontrolled infections Unstable angina, congestive heart failure (NYHA > class II), uncontrolled hypertension (diastolic >100 mmHg), uncontrolled cardiac arrhythmia, or recent (within 1 year) myocardial infarction History of arterial thrombosis (eg, stroke or transient ischemic attack) within the past year History of venous thrombosis that currently requires anti-coagulation therapy Received IL-11 within 4 weeks of the first dose of investigational product Have previously received any thrombopoietic growth factor Receipt of G-CSF, peg-G-CSF, or GM-CSF within 4 weeks of the first dose of investigational product Planned receipt of peg-G-CSF or GM-CSF after the first dose of investigational product Pregnant or breast feeding Subjects of reproductive potential who are not using adequate contraceptive precautions, in the judgment of the investigator. Amgen recommends double barrier contraception is used for all applicable patients enrolled on this study. A double barrier method is defined as two methods of contraception, for example 2 actual barrier methods, or one actual barrier method and one hormonal method. Known hypersensitivity to any recombinant E coli-derived product Any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures Subject currently is enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study(s) |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the incidence of clinically significant bleeding events. A clinically significant bleeding event is defined as any bleeding event of grade ≥ 2 per the modified WHO bleeding scale. Bleeding events that continue for more than 7 days will be counted as separate events every 8th day. Multiple bleeding events (eg epistaxis) that arise from one organ system on the same day will be collapsed into one single event. Simultaneous bleeding events from unique organ systems (eg gastrointestinal system and central nervous system) will be counted as unique events. |
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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 | 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 | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 110 |
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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I soggetti verranno seguiti per 60 mesi dopo la fine dello studio, fino alla perdita al follow-up, o decesso, (qualunque sia di piu' breve durata). |
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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 | 7 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 1 |