Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01438840




Registration number
NCT01438840
Ethics application status
Date submitted
19/09/2011
Date registered
22/09/2011
Date last updated
5/02/2018

Titles & IDs
Public title
Efficacy and Safety of Oral E5501 Plus Standard of Care for the Treatment of Thrombocytopenia in Adults With Chronic Immune Thrombocytopenia (Amendment 02)
Scientific title
A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Trial With an Open-label Extension Phase to Evaluate the Efficacy and Safety of Oral E5501 Plus Standard of Care for the Treatment of Thrombocytopenia in Adults With Chronic Immune Thrombocytopenia (Idiopathic Thrombocytopenia Purpura)
Secondary ID [1] 0 0
E5501-G000-302
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Thrombocytopenia 0 0
Immune Thrombocytopenia 0 0
Condition category
Condition code
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Standard of care

Active comparator: Avatrombopag (Core Study) - Avatrombopag will be administered orally as 5 mg, 10 mg, 20 mg, 30 mg, or 40 mg in a flexible dose design for 26 weeks. Participants will receive blinded therapy at a starting dose of 20 mg avatrombopag, one daily and allowed to have their dose titrated up (maximum dose of 40 mg avatrombopag) or down (minimum dose of 5 mg avatrombopag) depending on their response to study drug.

Placebo comparator: Placebo (Core Study) - Placebo will be administered as 5 mg, 10 mg, 20 mg, 30 mg or 40 mg in a flexible dose design for 26 weeks. Placebo will be administered orally at a starting dose of 20 mg, once daily. Afterwards the dose can be titrated up (maximum dose of 40 mg avatrombopag) or down (minimum dose of 5 mg avatrombopag) depending on the participant's response to the study drug; placebo titration will be used to maintain the blind.

Experimental: Avatrombopag (Open-Label Extension) - Participants who meet all eligibility criteria requirements of extension phase and who discontinue the core study because of lack of treatment effect will continue into the extension phase. Avatrombopag will be administered to participants who enter extension phase, with a starting dose of 20 mg avatrombopag, once daily for 76 weeks and undergo dose titration.


Treatment: Drugs: Standard of care
Permitted ITP concomitant background therapies are as follows:

* Corticosteroids and/or azathioprine taken at a stable dose for 4 weeks before randomization;
* Mycophenolate mofetil (MMF) or danazol taken at a stable dose for at least 12 weeks before randomization;
* Cyclosporine A (CsA) (due to the fact that it is a P-glycoprotein-mediated transport \[P-gp\] inhibitor) is to be avoided unless deemed medically necessary; CsA taken at a stable dose for at least 12 weeks before randomization.

At the discretion of the investigator, participants will be allowed to use aspirin, other salicylates, or approved adenosine diphosphate (ADP) receptor antagonists, (eg, clopidogrel, prasugrel) during the study once their platelet count had risen.

Participants treated with proton pump inhibitors (PPIs) and H2 antagonist therapy will receive a stable dose for at least 6 weeks prior to randomization. Treatment with these therapies must have been completed at least 2 weeks prior to randomization.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Weeks With Platelet Count Greater Than or Equal to 50 x 10^9/L During 6-Month Treatment Period
Timepoint [1] 0 0
Week 1 to Week 26
Secondary outcome [1] 0 0
Number of Participants With a Reduction in Use of Concomitant Immune/Idiopathic Thrombocytopenic Purpura (ITP) Medication
Timepoint [1] 0 0
Week 1 through Week 26
Secondary outcome [2] 0 0
Number of Participants With Platelet Count Greater Than or Equal to 50 x 10^9/L at Day 8
Timepoint [2] 0 0
Week 1 (Day 8)

Eligibility
Key inclusion criteria
1. Men and women greater than or equal to 18 years of age
2. Participants diagnosed with cITP (greater than or equal to 12 months duration) according to the American Society for Hematology/British Committee for Standards in Hematology (ASH/BCSH) guidelines, and an average of 2 platelet counts greater than 30x10^9/L). The physical exam should not suggest any disease which may cause thrombocytopenia other than ITP
3. Participants who previously received one or more ITP therapies (including, but not limited to corticosteroids, immunoglobulins, azathioprine, danazol, cyclophosphamide and/or rituximab).
4. Participants must have had either initially responded (platelet count greater than 50x10^9/L) to a previous ITP therapy or have had a bone marrow examination consistent with ITP within 3 years to rule out myelodysplastic syndrome (MDS) or other causes of thrombocytopenia
5. Prothrombin time/International Normalized Ratio (PT/INR) and activated partial thromboplastin time (aPTT) must have been within 80% to 120% of the normal range with no history of hypercoagulable state
6. A complete blood count within the reference range (including white blood count [WBC] differential not indicative of a disorder other than ITP), with the following exceptions: hemoglobin: participants with hemoglobin levels between 10 g/dL (100 g/L) and the lower limit of normal (LLN) are eligible for inclusion, if anemia was clearly attributable to ITP (excessive blood loss); Absolute neutrophil count (ANC) greater than or equal to 1500/uL (1.5x10^9/L) (elevated WBC/ANC due to corticosteroid treatment is acceptable)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Participants with known secondary immune thrombocytopenia (e.g., with known Helicobacter pylori-induced ITP participants infected with known human immunodeficiency virus [HIV] or hepatitis C virus [HCV] or participants with known systemic lupus erythematosus). (Revised per Amendment 01)
2. Participants with significant medical conditions that may impact on the safety of the participant or interpretation of the study results (e.g., acute hepatitis, active chronic hepatitis; lymphoproliferative disease; myeloproliferative disorders, leukemia)
3. History of MDS
4. History of gastric atrophy (added per Amendment 01)
5. History of pernicious anemia or participants with vitamin B12 deficiency (defined as less than LLN) who have not had pernicious anemia excluded as a cause (added per Amendment 01)
6. Any prior history of arterial or venous thrombosis (stroke, transient ischemic attack, myocardial infarction, deep vein thrombosis or pulmonary embolism), and more than two of the following risk factors: hormone replacement therapy, estrogen-containing hormone replacement or contraceptive therapies, smoking, diabetes, hypercholesterolemia, medication for hypertension, cancer, hereditary thrombophilic disorders (e.g., Factor V Leiden, antithrombin III deficiency, etc.), or any other family history of arterial or venous thrombosis
7. Participants with a history of significant cardiovascular disease (e.g., congestive heart failure [CHF] New York Heart Association Grade III/IV, arrhythmia known to increase the risk of thromboembolic events [e.g., atrial fibrillation], participants with a QT interval corrected for heart rate of >450 msec, angina, coronary artery stent placement, angioplasty, coronary artery bypass grafting)
8. Participants with a history of cirrhosis, portal hypertension, and chronic active hepatitis
9. Participants with concurrent malignant disease
10. Use of immunoglobulins (IVIg and anti-D) within 1 week of randomization
11. Splenectomy or use of rituximab within 12 weeks of randomization
12. Use of romiplostim or eltrombopag within 4 weeks of randomization
13. Participants who are currently treated with corticosteroids or azathioprine but have not been receiving a stable dose for at least 4 weeks prior to randomization or have not completed these therapies more than 4 weeks prior to randomization
14. Participants who are currently treated with MMF, CsA, or danazol but have not been receiving a stable dose for at least 12 weeks prior to randomization or have not completed these therapies more than 4 weeks prior to randomization
15. Use of cyclophosphamide or vinca alkaloid regimens within 4 weeks of randomization
16. Participants who are currently treated with PPIs or H2 antagonist therapy but have not been receiving a stable dose for at least 6 weeks prior to randomization or have not completed these therapies more than 2 weeks prior to randomization
17. Fasting gastrin-17 blood levels exceeding the ULN at Screening for participants not on PPIs or H2 antagonists (Revised per Amendment 01)
18. Fasting gastrin-17 blood levels exceeding 1.5 times the upper limit of normal (ULN) at Screening for participants on PPIs or H2 antagonists (Added per Amendment 01)
19. Blood creatinine exceeding ULN by more than 20% OR total albumin below the lower limit of normal (LLN) by 10%
20. Alanine aminotransferase (ALT) OR aspartate aminotransferase (AST) levels exceeding 3 times the ULN or total bilirubin exceeding 2 times the ULN
21. Participants with a history of cancer treatment with cytotoxic chemotherapy and/or radiotherapy.
22. Participants with a history of ITP treatment with cytotoxic chemotherapy are still eligible for enrollment.
23. Females who are pregnant (positive beta-human chorionic gonadotropin positive [B-hCG] test) or breastfeeding
24. Participants with a known allergy to avatrombopag (E5501) or its excipients

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
16/02/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/03/2014
Sample size
Target
Accrual to date
Final
49
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Adelaide
Recruitment hospital [2] 0 0
- Bedford Park
Recruitment postcode(s) [1] 0 0
- Adelaide
Recruitment postcode(s) [2] 0 0
- Bedford Park
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Antwerpen
Country [2] 0 0
Bulgaria
State/province [2] 0 0
Plovdiv
Country [3] 0 0
Bulgaria
State/province [3] 0 0
Sofia
Country [4] 0 0
Czechia
State/province [4] 0 0
Brno
Country [5] 0 0
Czechia
State/province [5] 0 0
Hradec Kralove
Country [6] 0 0
Czechia
State/province [6] 0 0
Praha
Country [7] 0 0
Netherlands
State/province [7] 0 0
Rotterdam
Country [8] 0 0
New Zealand
State/province [8] 0 0
Christchurch
Country [9] 0 0
New Zealand
State/province [9] 0 0
Palmerston North
Country [10] 0 0
Poland
State/province [10] 0 0
Bialystok
Country [11] 0 0
Poland
State/province [11] 0 0
Chorzow
Country [12] 0 0
Poland
State/province [12] 0 0
Gdansk
Country [13] 0 0
Poland
State/province [13] 0 0
Krakow
Country [14] 0 0
Poland
State/province [14] 0 0
Lodz
Country [15] 0 0
Poland
State/province [15] 0 0
Wroclaw
Country [16] 0 0
Singapore
State/province [16] 0 0
Singapore
Country [17] 0 0
Slovakia
State/province [17] 0 0
Bratislava
Country [18] 0 0
South Africa
State/province [18] 0 0
Johannesburg
Country [19] 0 0
Ukraine
State/province [19] 0 0
Dnipropetrovsk
Country [20] 0 0
Ukraine
State/province [20] 0 0
Donetsk
Country [21] 0 0
Ukraine
State/province [21] 0 0
Ivano-Frankivsk
Country [22] 0 0
Ukraine
State/province [22] 0 0
Kyiv
Country [23] 0 0
Ukraine
State/province [23] 0 0
Lviv

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Eisai Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Joe McIntosh
Address 0 0
Eisai Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT01438840