Essential Thrombocythaemia Clinical Trial
Official 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
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 unblind a patient (e.g. due to safety reasons), the
above mentioned (in this section) envelopes will be used.
Only treatment naïve subjects, in respect to cytoreductive drugs with confirmed diagnosis of
ET (centralized re-evaluation according to WHO, 2008; see Section 6.2.1) and assessment of
JAK-2 status (centralized re-evaluation of JAK-2 status; see Section 6.2.2) will be
enrolled.
As described above, stage I of the study will be considered as closed as soon as 140
subjects have been recruited. The duration of stage II depends on the result of the
re-assessment of sample size.
Once stage I is finished, stage I subjects will enter into an extension period for a maximum
of three years.
n/a
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Prevention
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
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Phase 3 | |
| Completed |
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Phase 2 |