NCT01230775: ARETA

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

Completed Phase 3 Last updated 25 May 2016

What this trial tests

Phase 3 trial testing Anagrelide retard in Essential Thrombocythaemia in 146 participants. Completed in 1 January 2015.

Timeline

1 December 2010

Primary endpoint
1 January 2015

1 January 2015

Quick facts

Lead sponsor	AOP Orphan Pharmaceuticals AG
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	prevention
Enrollment	146
Start date	1 December 2010
Primary completion	1 January 2015
Estimated completion	1 January 2015
Sites	37 locations across Austria, Bulgaria, Croatia, Lithuania, Poland, Romania, Russia, Slovakia

Drugs / interventions tested

• Anagrelide retard — full drug profile →
• Placebo

Conditions studied

• Essential Thrombocythaemia — all drugs for Essential Thrombocythaemia →

Sponsor

AOP Orphan Pharmaceuticals AG — full company profile →

Who can join

Adults 18 to 60, any sex, with Essential Thrombocythaemia. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Time to 1st clinically significant ET related event
  Time frame: beginning 2012

Sponsor's own description

This is a multicenter, phase III, randomized, subject and sponsor-blinded, placebo-controlled study to determine the treatment effect of "Anagrelide retard" in subjects with Essential Thrombocythaemia (ET) at "defined risk" (definition of risk criteria: see Inclusion Criteria Section 5.1) The study is planned as a 2-stage procedure according to Bauer and Köhne: After recruitment of 140 subjects an interim analysis with re-assessment of sample size is planned in an adaptive manner.

As the confirmatory analysis will be based on a time-to-event evaluation (i.e. time to 1st clinically significant ET related event), there is no stipulated observation time identically applying for all subjects. Yet, with an interim analysis being performed after having recruited 140 subjects - which is expected to be reached after 1 year - the estimated observation time for a subject in stage I will also be about 1 year. (Details are explained in the section "Statistical Considerations").

Subjects will be randomized in a 1:1 ratio to one of the following two arms:

Group A: Anagrelide retard Group B: Placebo

An a priori stratification is planned for the JAK-2 mutational status. For exploratory purposes a post hoc stratification is used for obtaining covariate adjusted results, for the following other potentially predictive factors: sex, age, Factor V Leiden, and BMI.

Dosing will be started with 1 tablet per day for week 1 and will be titrated up according to response (platelet reduction) to 2 tablets in week 2. Dosing may be further increased or decreased according to platelet response in week 3 and 4. However, the maximum dose is 4 tablets (=8mg) per day. After week 4, the maximum dose to achieve optimal platelet counts (\<450 G/L) should be maintained (for visit schedule see study flow chart section IV).

To verify a treatment response, platelet counts must be evaluated at every visit. The platelet count values will be withheld from the subjects for the duration of stage I or stage II respectively. The subjects have to agree explicitly to this procedure by signing the Informed Consent form.

This is a patient and sponsor-blinded clinical study. The trial medical is packaged in the blinded fashion to keep the patient unaware (blinded) towards the actual treatment group they were randomized to. The sponsor functions (including medical monitor, pharmacovigilance manager, clinical project manager, trial data manager and trial statistician) with stay blinded in the course of the study until the database lock. Randomization scheme will be prepared by an independent statistician (not otherwise involved in the study), and will be stored securely with no access to it by the sponsor functions mentioned above. The process of randomization (provision of the individual drug-allocation information to the subjects) will be carried out by a trained staff by Harrison, in adherence to the procedures to keep the other blinded functions unaware of this information (blinded). Unblinding envelopes, which contain the treatment code per patient number for identification of treatment in case when a safety-relevant unblinding needed, will be stored at the sponsor's site. At the end of the study, verification of the extent of maintaining the blind by checking if the envelopes have been broken, will take place and will be properly documented. If the sealed envelope will broken to provide treatment identification, the date of breaking the code, the initials of the person who broke the code and the reason will be stated on the envelope.

The operational details on the blinding procedures are outlined in the relevant working guidelines (ARETA Study Working Guideline for idv staff and ARETA Study Working Guideline for Harrison, each in its current version).

Investigator will not be blinded in this study, i.e. in case of a medical need individual patient management will be driven by the full knowledge of the trial related interventions. For the case, the sponsor will need to

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Pharmacokinetics of a Novel Anagrelide Extended-Release Formulation in Healthy Subjects: Food Intake and Comparison With a Reference Product.
   Petrides PE, Schoergenhofer C, Widmann R, Jilma B, et al · · 2018 · cited 4× · PMID 28301098 · DOI 10.1002/cpdd.340