Anagrelide Retard in Essential Thrombocythemia (TEAM-ET)

AOP Orphan

Status and phase

Completed

Phase 3

Conditions

Essential Thrombocythemia

Treatments

Drug: Thromboreductin

Drug: Anagrelide retard

Study type

Interventional

Funder types

Industry

Identifiers

NCT02076815

2013-003410-41 (EudraCT Number)

AOP18007

Details and patient eligibility

About

The purpose of this study is determine whether Anagrelide Retard is non-inferior to anagrelide immediate release form in treatment of essential thrombocythemia.

Essential thrombocythemia (ET) is a myeloproliferative neoplasm characterised by a sustained increase in platelet counts above the normal value (> 450 x 109/L) and increased megakaryopoiesis in the bone marrow, without secondary causes of thrombocytosis.

Anagrelide hydrochloride selectively reduces platelet numbers by inhibiting megakaryocyte development and maturation in humans, without affecting other cell lineages.

Anagrelide Retard is a new, prolonged release (PR) tablet formulation of anagrelide developed by AOP Orphan Pharmaceuticals AG. The rationale for developing this new formulation is based on the assumption of having a better tolerability while maintaining an efficacy comparable to that of the immediate release formulation.

The effects of Anagrelide Retard and Thromboreductin® will be compared in terms of mean platelet count measured by a central laboratory/centralized method at 3 time points during the maintenance phase.

Full description

This is a randomised, multicentre, double-blind, active controlled study to compare the efficacy and safety of two different anagrelide formulations in patients with high-risk essential thrombocythemia (ET).

100 patients, either Anagrelide-treated or Anagrelide-naïve, with an indication to receive Thromboreductin® treatment, will be randomized into one of the two investigational medicinal product (IMP) groups (Anagrelide Retard or Thromboreductin®). Treatment allocation will be balanced within stratum (treated/naive) and age classes by central randomization. Naive patients will start with dose level 2 of the IMPs (i.e., 1 mg Thromboreductin® or 2 mg Anagrelide Retard). Anagrelide-treated patients will be switched to the dose level which is closest to the pre-study anagrelide dose at study start. Dose modifications in the titration phase will be done on a weekly basis (up to a maximum of 12 weeks) until "stable platelet counts" on two consecutive visits is achieved.

The periods of the study participation per patient are as follows:

Screening (up to 7 days prior to randomization), ending with randomization/first IMP dose (Baseline Visit)
Titration period (weekly visits for up to 12 weeks): to achieve "stable platelet counts" on two consecutive measurements (i.e. weekly visits)
Maintenance period (weekly visits for 4 weeks): primary endpoint relevant period. The maintenance period for a patient starts at the visit with the second successive platelet count ≤400 G/L (or <600 G/L, if the dose cannot be increased any more due to intolerance or because the maximal dose allowed has already been reached) if the second platelet value measured lies in the range within ± 30% of the value measured at the previous visit.
End of study (EoS) safety follow-up visit (28 days after the last maintenance visit/EoT for early termination).

Enrollment

106 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

willing and able to give written informed consent prior to any study specific procedures and able to comply with the trial protocol
confirmed diagnosis of ET according to 2008 WHO diagnostic criteria* (Swerdlow et al, 2008), defined as meeting all four criteria
at high risk of experiencing ET-related events, indicated for Thromboreductin® treatment as defined by one or more of the following criteria: age ≥ 60 years, platelet counts ≥ 1000 G/L, increase of platelet count ≥ 300 G/L within 3 months, severe thrombohemorrhagic or ischemic symptoms in anamnesis
either currently treated with anagrelide
or ET treatment naive
or anagrelide naive

Exclusion criteria

Diagnosis of any myeloproliferative disorder other than ET
Any known cause for a secondary thrombocytosis
ET currently well controlled by another cytoreductive treatment than Anagrelide and the opportunity to continue to receive this treatment
ET currently treated with combination of any two of the following agents: anagrelide, hydroxyurea, interferons, busulfan
Hypersensitivity to either active or non-active ingredients of anagrelide or to any other excipients of the investigational products
Known hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption
Cardiovascular disease grade 3 with a negative benefit/risk assessment or grade 4 (South West Oncology Group; Green and Weiss, 1992)
Clinically significant abnormal laboratory values (excluding markers for ET) in investigator's opinion
Severe renal insufficiency (creatinine clearance <30 ml/min)
Moderate to severe hepatic insufficiency (ALT or AST > 5 times upper normal limit [UNL])
White blood count (WBC) ≥ 15 G/L at screening
Diagnosis of any malignancy, other than ET (except basal cell and squamous cell carcinomas of the skin and carcinoma in situ of the cervix that have been completely excised and are considered cured), within the last 3 years, or coexisting malignant, systemic disease
Poorly controlled diabetes mellitus
Known infection with hepatitis B, hepatitis C or HIV
Pregnant or lactating women
Women of childbearing potential or male patients, who have sexual intercourse with females of childbearing potential, not willing to use an effective method of contraception during the study.
History of drug/alcohol abuse within the previous 2 years
Participation in another investigational study within 4 weeks prior to informed consent signed or for a longer duration if specified in local regulations
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.