E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
male and female "at risk" subjects with Essential Thrombocythaemia |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10015493 |
E.1.2 | Term | Essential thrombocythaemia |
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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 determine whether "Anagrelide retard" compared to placebo will reduce the rate of ET-related complications in subjects with potential risk for ET-related Events |
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E.2.2 | Secondary objectives of the trial |
to assess the effect of "Anagrelide retard" compared to placebo on the following: - reduction of platelet count - response rates - change to "high risk status" - cardiovascular safety - Quality of Life |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Willing and able to give written informed consent prior to any study specific procedures and able to comply with this protocol • Male or female subjects aged between 18 and 60 years, • Confirmed diagnosis of ET according to WHO-criteria (2008) including assessment of JAK-2 status. • Presence of predisposing risk factors for ET related events confirmed by clinical or laboratory results:
- Platelet count < 1.000 G/L additionally at least ONE of the following criteria has to be fulfilled: - Subjects aged between 40 and 60 years or - Subjects with ET and disease duration > 3 years (Diagnosis of ET has to be at least 3 years ago and confirmed at time of screening) or - Subjects with ONE of the following risk factors for thrombotic complications: a) JAK- 2 positivity, b) Protein C and/or Protein S deficiency, c) Antithrombin III deficiency, d) Factor V Leiden or Prothrombin mutation, e) Cardiovascular risk factors: Essential hypertension; Smoking (>5 cigarettes/d), Obesity (BMI>30), Cholesterol (HDL/LDL ratio < 4); Hormone replacement therapy; hormonal contraception
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E.4 | Principal exclusion criteria |
• Diagnosis of any other myeloproliferative disorder • High-risk status (age > 60 years, platelet count ≥ 1.000 G/L, increase of platelet count > 300 G/L within 3 month, history of thrombotic/haemorhagic or ischemic complications). • Any known cause for a secondary thrombocytosis • Previous or current treatment of ET with cytoreductive therapy • Diagnosis of any malignancy, apart from ET, within the last 3 years • Known or suspected intolerance to the investigational products • Known or suspected congestive heart failure • WBC ≥ 15 G/L • Severe renal impairment (creatinine clearance <30 ml/min) • Severe liver impairment (ALT or AST >5 times normal) • Clinically significant abnormal laboratory values (excluding markers of essential thrombocythaemia) • Poorly controlled diabetes mellitus • Infection with hepatitis B, hepatitis C or HIV • Subjects with a history of drug/alcohol abuse (within the previous 2 years) • Participation in another investigational study within 6 months prior to enrolment or for a longer duration if specified in local regulations • Women of childbearing potential with inadequate contraception • Pregnant or lactating women (pregnancy test to be assessed within 7 days prior to study treatment start) • Any significant psychiatric disorder that, in the opinion of the investigator, might prohibit the understanding and giving of informed consent or that might prevent the subject from completing the trial.
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to the 1st clinically significant ET related event |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | Yes |
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 | Yes |
E.6.10 | Pharmacogenetic | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
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 | 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 | 4 |
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 | 4 |
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 |