Anagrelide Retard vs. Placebo: Efficacy and Safety in "At-risk" Patients With Essential Thrombocythaemia

• Register: ClinicalTrials.gov
• Last refreshed on: 11 March 2013
• Main ID: NCT01230775
• Date of registration: 28/10/2010
• Primary sponsor: AOP Orphan Pharmaceuticals AG
• Public title: Anagrelide Retard vs. Placebo: Efficacy and Safety in "At-risk" Patients With Essential Thrombocythaemia ARETA
• Scientific title: A Phase III, Randomized, Multicenter, Subject and Sponsor-blinded, Placebo Controlled Study to Compare the Efficacy and Safety of "Anagrelide Retard" Versus Placebo in "at Risk" Subjects With Essential Thrombocythaemia
• Date of first enrolment: December 2010
• Target sample size: 280
• Recruitment status: Recruiting
• URL: http://clinicaltrials.gov/show/NCT01230775
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Prevention

Countries of recruitment

Austria, Bulgaria, Croatia, Lithuania, Poland, Romania, Russian Federation, Slovakia, Slovenia, Turkey, Ukraine

Contacts

• Name: Michael Zörer

• Name: Oleh Zahriychuk, MD
• Affiliation: AOP Orphan Pharmaceuticals AG

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Willing and able to give written informed consent prior to any study specific
procedures and able to comply with this protocol

2. Male or female subjects aged between 18 and 60 years,

3. Confirmed diagnosis of ET according to WHO-criteria 2008 (Appendix A) including
assessment of JAK-2 status (central re-evaluation).

4. Presence of predisposing risk factors for ET related events confirmed by clinical or
laboratory results:

Definition of subjects with potential risk for ET-related Events:

- 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:

- JAK- 2 positivity

- Protein C and/or Protein S deficiency

- Antithrombin III deficiency

- Factor V Leiden or Prothrombin mutation

- Cardiovascular risk factors:

- Essential hypertension,

- Smoking (>5 cigarettes/d),

- Obesity (BMI>30),

- Cholesterol (HDL/LDL ratio < 4),

- Hormone replacement therapy,

- Hormonal contraception.

Exclusion Criteria:

1. Diagnosis of any other myeloproliferative disorder

2. 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/haemorrhagic or ischemic
complications).

3. Any known cause for a secondary thrombocytosis

4. Previous or current treatment of ET with cytoreductive therapy

5. Diagnosis of any malignancy, apart from ET, within the last 3 years

6. Known or suspected intolerance to the investigational product

7. Known or suspected congestive heart failure

8. WBC = 15 G/L

9. Severe renal impairment (creatinine clearance <30 ml/min)

10. Severe liver impairment (ALT or AST >5 times normal)

11. Clinically significant abnormal laboratory values (excluding markers of essential
thrombocythaemia)

12. Poorly controlled diabetes mellitus

13. Infection with hepatitis B, hepatitis C or HIV

14. Subjects with a history of drug/alcohol abuse (within the previous 2 years)

15. Participation in another investigational study within 6 months prior to enrolment or
for a longer duration if specified in local regulations

16. Women of childbearing potential with inadequate contraception

17. Pregnant or lactating women (pregnancy test to be assessed within 7 days prior to
study treatment start)

18. 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.

Women of childbearing potential with inadequate contraception; women with child-bearing
potential, receiving oral hormone contraception and aiming to participate in the study,
will have to apply an additional effective method of contraception during the study
period; male subjects, receiving investigational medicinal product, which have sexual
intercourse with females of childbearing potential, should use medically acceptable and
reliable method of contraception to prevent pregnancy.



Age minimum: 18 Years
Age maximum: 60 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Essential Thrombocythaemia

Intervention(s)

Drug: Anagrelide retard

Drug: Placebo

Primary Outcome(s)

Time to 1st clinically significant ET related event [Time Frame: beginning 2012]

Secondary Outcome(s)

Efficacy and safety [Time Frame: end 2013]

Secondary ID(s)

AOP13007

Source(s) of Monetary Support

Please refer to primary and secondary sponsors