male or female patients with confirmed diagnosis of Essential Thrombocythemia MedDRA version: 17.0 Level: LLT Classification code 10015494 Term: Essential thrombocythemia System Organ Class: 100000004864
Conditions
Interventions
Product Name: Anagrelide Retard 2 mg film coated tablet (over-encapsulated for blinding)
Product Code: ANAT2
Pharmaceutical Form: Capsule
INN or Proposed INN: Anagrelide
CAS Number: 58579-51-4
Other d
Sponsors
AOP Orphan Pharmaceuticals AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Willing and able to give written informed consent prior to any study specific procedures and able to comply with this protocol. • Male / female • Age =18 years • Confirmed diagnosis of ET according to 2008 World Health Organization (WHO) diagnostic criteria*, defined as meeting all four criteria as follows: a. Sustained platelet count =450 G/L. b. Bone marrow biopsy specimen showing proliferation mainly of the megakaryocytic lineage with increased numbers of enlarged, mature megakaryocytes. No significant increase or left shift of neutrophil granulopoiesis or erythropoiesis. (Bone marrow examination should be available as source data and based on existing biopsies – no screening assessment.) c. Not meeting WHO criteria for polycythemia vera, primary myelofibrosis, BCR-ABL1-positive chronic myelogenous leukemia, myelodysplastic syndrome, or other myeloid neoplasm. d. Demonstration of JAK2V617F or other clonal marker, or in the absence of JAK2V617F, no evidence for reactive thrombocytosis. * If the diagnosis was made according to earlier criteria (for example, Polycythemia Vera Study Group [PVSG]), re-examination and confirmation of diagnosis according to 2008 WHO criteria must be done. In the source data a notice by investigator should be made: ‘Reclassified according to WHO 2008 criteria for ET’. AND: • at high risk of experiencing ET-related events, indicated for Thromboreductin® treatment as defined by one or more of the following criteria: o Age = 60 years o Platelet counts = 1000 G/L o Increase of platelet count = 300 G/L within 3 months o Severe thrombohemorrhagic or ischemic symptoms in anamnesis EITHER: • Currently treated with anagrelide (Thromboreductin® or other locally available anagrelide formulations), meeting the definition of well controlled disease. Well controlled disease is defined as the absence at screening of any acute disease related symptoms, as well as the achievement of stable platelet counts (=65 years) yes F.1.3.1 Number of subjects for this age range 67
Exclusion criteria
Exclusion criteria: • Diagnosis of any other myeloproliferative disorder • Any known cause for a secondary thrombocytosis, e.g. thrombocytosis due to iron deficiency • ET currently well controlled by another cytoreductive treatment than Anagrelide (e.g. hydroxyurea, busulfan, IFN) 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, see Appendix 6) • Clinically significant abnormal laboratory values (excluding markers for ET) in investigator’s opinion, including electrolyte imbalance • Severe renal insufficiency (creatinine clearance 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 (pregnancy test to be performed within 7 days prior study treatment start) • 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. Effective methods for women are hormonal contraceptives, intrauterine devices (IUDs), surgical intervention, and sexual abstinence. Female patients with childbearing potential receiving oral hormonal contraception will have to apply an additional effective method of contraception during the study period. Effective methods for men are condoms and sexual abstinence. • 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine whether Anagrelide Retard is non-inferior to Thromboreductin® in terms of mean platelet count measured by a central laboratory/centralized method at 3 time points during the maintenance phase.;Secondary Objective: To compare the effects of Anagrelide Retard and Thromboreductin® on the following: - platelet response status - tolerability and safety ;Primary end point(s): • Mean platelet count based on three measurements during the maintenance phase. Optimal dosing (increase to achieve the target platelet level, decrease in case of toxicity, following the SmPC specifications of Thromboreductin® and the dosing rules for Anagrelide Retard) should be applied to each patient to reduce (for anagrelide naive patients) or maintain (for anagrelide pre-treated patients) the platelet count =400 G/L or, in cases in which further dose up-titration is not possible due to poor tolerability, at least below 600 G/L. ;Timepoint(s) of evaluation of this end point: Mean platelet count based on three measurements during the maintenance phase; Visit 14, Visit 16 & Visit 18 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy • Platelet response status: Responder: Response is defined as the attainment of platelet levels <600 G/L (response will be evaluated by taking the mean of three platelet counts from the central laboratory) during the maintenance treatment period. Non responder: If platelet levels do not remain <600 G/L or missing values (e.g. drop-outs during titration and maintenance phase). • Time from randomization to entering maintenance phase • Study drug administration (the maintenance dose and the number of titrations) • Change in platelet counts in the titration phase • Time from randomization until withdrawal Safety • Incidence, causality and intensity of adverse events (AEs) according to common terminology criteria for adverse events (CTCAE 4.0), with additional special focus on cardiovascular, neurological and general disorders (adverse events of special interest, AESI: palpitation, tachycardia, headache, dizziness, nausea, vomiting, diarrhea, abdominal pain) • Incidence, intensity and outcomes of events leading to dose reduction or temporary or permanent treatment discontinuation • Need of medications (dose and duration) to treat AEs • Electrocardiogram (ECG) abnormalities • Ejection fraction and echocardiography (ECHO) overall conclusion (normal/abnormal) Patient reported outcomes • Quality of Life (EQ-5D-3L) Pharmacokinetic measurements There will be a mandatory PK sampling (at three visits during the maintenance period: Visits M1, M3 and M5) and an optional PK sampling (at the second visit in the maintenance period: Visit M2) to determine the concentration of anagrelide in plasma. ;Timepoint(s) of evaluation of this end point: Efficacy: Evaluation of platelet status will be done throughout the Titration Period and the Maintainance Phase Safety: Evaluation of safety aspects status will be done throughout the complete study Patient reported outcomes: Evaluation of Quality of Life Questionnaire will b | — |
Countries
Austria, Bulgaria, Lithuania, Poland, Russian Federation
Contacts
Public ContactMedical Affairs Manager
AOP Orphan Pharmaceuticals AG
Outcome results
None listed