Clinical trial for comparison of anagrelide retard versus placebo in subjects with Essential Thrombocythaemia.

• Conditions: male and female at risk patients with Essential Thrombocythaemia; MedDRA version: 17.0Level: PTClassification code 10015493Term: Essential thrombocythaemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2009-017095-24-LT
• Lead Sponsor: AOP Orphan Pharmaceuticals AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-06-18
• Last Update Posted: 26 January 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 240

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 patients 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 240
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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) in investigator's opinion, including electrolytes disbalance
• 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 patient from completing the trial.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine whether Anagrelide retard compared to placebo will reduce ET-related complications in subjects with potential risk for ET-related Events;Secondary Objective: to assess the effect of Anagrelide retard compared to placebo on the following:<br>- reduction of platelet count <br>- response rates<br>- change to high risk status<br>- cardiovascular safety<br>- Quality of Life;Primary end point(s): Time to the 1st clinically significant ET related event;Timepoint(s) of evaluation of this end point: The main part of the study is planned as a 2-stage procedure according<br>to Bauer and Köhne. After recruitment of 140 subjects an interim<br>analysis with re-assessment of sample size is performed.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Efficacy<br>- reduction of platelet counts<br>- occurrence of change to high risk” status<br>(i.e. platelets > 1.000 G/L or occurrence of an ET related event)<br>- number of subjects achieving a complete response<br>Safety<br>- Adverse Events<br>- cardiovascular safety (assessed by ECG, ECHO, NT-proBNP or<br>BNP)<br>Quality of Life: SF-36;Timepoint(s) of evaluation of this end point: The main part of the study is planned as a 2-stage procedure according<br>to Bauer and Köhne. After recruitment of 140 subjects an interim<br>analysis with re-assessment of sample size is performed.