Essential ThrombocythemiaPhase 3TEAM-ETNCT02076815
Anagrelide Retard in Essential Thrombocythemia
A Phase 3 study testing Anagrelide retard and Thromboreductin in people with Essential Thrombocythemia, run by AOP Orphan Pharmaceuticals AG at 19 sites in 5 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Essential Thrombocythemia
- What is being tested?
- Anagrelide retard and Thromboreductin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 106 participants
- Where
- 19 sitesin 5 countries
- Study dates
- Feb 2014to Apr 2015
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 19Show fewer
- 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.
Trial locations and contacts
19 sites in 5 countries.
19 sites in 5 countries
Poland6 sites
AOP Orphan Investigational Site Poland 5
Bialystok, 15-276
AOP Orphan Insvestigational Site Poland 6
Gdansk, 80-952
AOP Orphan Investigational Site Poland 4
Katowice, 40-027
AOP Orphan Investigational Site Poland 3
Lublin, 20-081
AOP Orphan Investigational Site Poland 2
Torun, 87-100
AOP Orphan Investigational Site Poland 1
Warsaw, 02-776
Russia6 sites
AOP Orphan Investigational Site Russia 1
Moscow, 125167
AOP Orphan Investigational Site Russia 2
Saint Petersburg, 191024
AOP Orphan Investigational Site Russia 5
Saint Petersburg, 194291
AOP Orphan Investigational Site Russia 4
Saint Petersburg, 196084
AOP Orphan Investigational Site Russia 6
Volgograd, 400138
AOP Orphan Investigational Site Russia 3
Yaroslavl, 150062
Austria3 sites
AOP Orphan Investigational Site Austria 2
Linz, A-4040
AOP Orphan Investigational Site Austria 1
Vienna, A-1090
AOP Orphan Investigational Site Austria 3
Wels, A-4600
Bulgaria2 sites
AOP Orphan Investigational Site Bulgaria 1
Pleven, 5800
AOP Orphan Investigational Site Bulgaria 2
Sofia, 1407
Lithuania2 sites
AOP Orphan Investigational Site Lithuania 1
Kaunas, LT-50009
AOP Orphan Investigational Site Lithuania 2
Klaipėda, LT-92288
About this study
Official title: A Phase III Randomized, Multicenter, Double-blind, Active Controlled Study to Compare the Efficacy and Safety of Two Different Anagrelide Formulations in Patients With Essential Thrombocythemia (TEAM-ET 2.0)
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.
Read more
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.
Read the detailed 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).
- Conditions
- Essential Thrombocythemia
- Being tested
- Anagrelide retard, Thromboreductin
- Keywords
- myeloproliferative neoplasm, essential thrombocythemia, high risk patients, anagrelide
- Medical subject headings
- Thrombocythemia, Essential, Myeloproliferative Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anagrelide retardDrug
Also called Anagrelide retard 2 mg film coated tablet, ANAT2
Overencapsulated tablets or matched placebo, twice daily, 2-12 weeks titration to achieve stable platelet count, followed by 4 more weeks
ThromboreductinDrug
Also called Anagrelide 0.5 mg capsule, ANAC05
Overencapsulated capsule, twice daily, 2-12 weeks titration to achieve the stable platelet count, followed by 4 more weeks
| Study group | Role | What they receive |
|---|---|---|
| Anagrelide retard | Experimental | Anagrelide Retard prolonged-release formulation Receives: Drug: Anagrelide retard |
| Thromboreductin | Active comparator | Anagrelide immediate release formulation Receives: Drug: Thromboreductin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Platelet count
Mean value from three measurements
Measured: weeks 13-17
Secondary outcomes (11)
platelet response
Measured: weeks 13-17
Time from randomization to entering maintenance period
Measured: up to 12 weeks
Study drug administration
Measured: weeks 1-17
Change in platelet counts in the titration period
Measured: baseline, week 12
Time from randomization until withdrawal
Measured: up to 17 weeks
Incidence, causality and intensity of adverse events
Measured: weeks 0-21
Incidence, intensity and outcomes of events leading to dose reduction or temporary or permanent treatment discontinuation
Measured: weeks 1-18
Need of medications to treat adverse events
Measured: weeks 0-21
ECG abnormalities
Measured: weeks 0-18
Ejection fraction
Measured: baseline, week 17, week 21
ECHO normal/abnormal
Measured: baseline, week 17, week 21
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2014 (estimated)
- Study startFeb 2014
- Primary completionFeb 2015
- Study completionApr 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Essential ThrombocythemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 106 participants (actual)
Sponsor and investigators
- Lead sponsor
- AOP Orphan Pharmaceuticals AG
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Heinz Gisslinger, Prof., MD, Principal investigator, Vienna Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02076815
- Sponsor's protocol ID
- AOP18007
- Other IDs
- 2013-003410-41
- Acronym
- TEAM-ET
- Status last verified
- Jul 2015
- First submitted
- 13 Feb 2014
- Last updated
- 29 Jul 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Randomized, Multicenter, Double-blind, Active Controlled Study to Compare the Efficacy and Safety of Two Different Anagrelide Formulations in Patients With Essential Thrombocythemia (TEAM-ET 2.0)
- ClinicalTrials.gov ID
- NCT02076815
- Acronym / sponsor ID
- TEAM-ET / AOP18007
- Conditions
- Essential Thrombocythemia
- Keywords
- myeloproliferative neoplasm, essential thrombocythemia, high risk patients, anagrelide
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 106 participants (actual)
- Lead sponsor
- AOP Orphan Pharmaceuticals AGIndustry (pharma, biotech, devices)
- Study start
- Feb 2014
- Primary completion
- Feb 2015 (actual)
- Study completion
- Apr 2015 (actual)
- First posted
- 4 Mar 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Anagrelide retard | Experimental | Drug: Anagrelide retardAnagrelide Retard prolonged-release formulation |
| Thromboreductin | Active comparator | Drug: ThromboreductinAnagrelide immediate release formulation |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Anagrelide retardAlso: Anagrelide retard 2 mg film coated tablet, ANAT2Overencapsulated tablets or matched placebo, twice daily, 2-12 weeks titration to achieve stable platelet count, followed by 4 more weeks | Drug | Anagrelide retard |
| ThromboreductinAlso: Anagrelide 0.5 mg capsule, ANAC05Overencapsulated capsule, twice daily, 2-12 weeks titration to achieve the stable platelet count, followed by 4 more weeks | Drug | Thromboreductin |
Primary outcome
Platelet count
Time frame: weeks 13-17
Mean value from three measurements
11 secondary outcomes
platelet response
Time frame: weeks 13-17
Time from randomization to entering maintenance period
Time frame: up to 12 weeks
Study drug administration
Time frame: weeks 1-17
Change in platelet counts in the titration period
Time frame: baseline, week 12
Time from randomization until withdrawal
Time frame: up to 17 weeks
Incidence, causality and intensity of adverse events
Time frame: weeks 0-21
Incidence, intensity and outcomes of events leading to dose reduction or temporary or permanent treatment discontinuation
Time frame: weeks 1-18
Need of medications to treat adverse events
Time frame: weeks 0-21
ECG abnormalities
Time frame: weeks 0-18
Ejection fraction
Time frame: baseline, week 17, week 21
ECHO normal/abnormal
Time frame: baseline, week 17, week 21
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Heinz Gisslinger, Prof., MD principal investigator
Vienna Medical University
19 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Anagrelide retard and Thromboreductin in people with Essential Thrombocythemia, run by AOP Orphan Pharmaceuticals AG at 19 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in Poland, Russia, Austria, Bulgaria, Lithuania. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Platelet count (time frame: weeks 13-17). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jul 2015.