CClinicalTrials.gg
TerminatedNCT01433978Updated Feb 6, 2018Results posted

A Phase 3, Multicenter, Randomized, Double-blind,Active-controlled, Parallel-group Trial With an Open-labelExtension Phase to Evaluate the Efficacy and Safety of OralE5501 Versus Eltrombopag, in Adults With Chronic ImmuneThrombocytopenia (Idiopathic Thrombocytopenic Purpura)

A Phase 3 interventional study of Eltrombopag and Avatrombopag in Idiopathic Thrombocytopenic Purpura, sponsored by Eisai Inc.. Terminated at 1 site in United States. Open to participants aged 18 Years to 99 Years. Per ClinicalTrials.gov, last updated 2018-02-06.

Sponsored by Eisai Inc. · Phase 3, Interventional, and Treatment

Why this study was terminated
Study was terminated early due to significant enrollment challenges.
Phase
Phase 3
Study type
Interventional
Enrollment
24
Allocation
Randomized
Ages
18 Years to 99 Years
Sex
All
01

Study summary

Core study:

To compare the efficacy of avatrombopag (in addition to standard) of care to eltrombopag (in addition to standard of care) for the treatment of adult participants with chronic immune thrombocytopenia (idiopathic thrombocytopenic purpura [ITP]) as measured by durable platelet response.

Open-label Extension Phase:

To evaluate the safety and tolerability of long-term therapy with avatrombopag in participants with chronic ITP (cITP).

Read the detailed description

The study consists of three phases: Prerandomization, Randomization (Core Study) and Extension Phase. Participants 18 years of age and over, who meet all the eligibility requirements will be randomized into the study. It will require that splenectomized participants make up at least 35% of the study population and no single platelet count is greater than 35x10\^9/L. Participants will be centrally stratified at randomization by splenectomy status, baseline platelet count, and use of concomitant ITP medication at baseline and randomized to receive either double-blind avatrombopag or eltrombopag in a 1:1 ratio. Participants will receive blinded therapy at a starting dose of 20 mg avatrombopag once daily or 50 mg eltrombopag once daily. Participants will be allowed to have their dose titrated up (maximum dose 40 mg avatrombopag and 75 mg for eltrombopag) or down (minimum dose 5 mg for avatrombopag and 25 mg for eltrombopag) depending on their response to study drug. The goal of dose modification is to maintain the platelet count at levels greater than or equal to 50x10\^9/L and less than or equal to 150x10\^9/L, and to decrease the need for ITP-directed concomitant medications. The duration of treatment in the Core study and the Extension Phase is approximately 26 and 104 weeks, respectively.

02

Conditions studied

03

In context

Purpura

263 studies on the registry are indexed under Purpura; 27 are open to participants now.

This study's enrollment of 24 is below the median of 50 across 171 interventional studies indexed under Purpura.

Browse Purpura studies →

Lead sponsor

Eisai Inc. is the lead sponsor of 360 studies on the registry; 7 are open to participants now.

Of its 81 completed or terminated interventional studies of FDA-regulated products, 54 (67%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 99 Years
Sexes eligible
All
Accepts healthy volunteers
No

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 less 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: a) 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); b) Absolute neutrophil count (ANC) greater than or equal to 1500/uL (1.5x10\^9/L) (elevated WBC/ANC due to corticosteroid treatment is acceptable).

Exclusion criteria

Exclusion Criteria:

Core Study

  1. Participants with known secondary immune thrombocytopenia (e.g., participants with known Helicobacter pylori-induced ITP, infected with known human immunodeficiency virus [HIV] or hepatitis C virus [HCV] or with known systemic lupus erythematosus [SLE]).
  2. Participants considered unable, or unwilling to comply with the study protocol requirements or give informed consent, as determined by the investigator.
  3. Participants with significant medical conditions that may impact the safety of the participant or interpretation of the study results (e.g., acute hepatitis, active chronic hepatitis; lymphoproliferative disease; myeloproliferative disorders, leukemia).
  4. History of MDS.
  5. History of pernicious anemia or participants with vitamin B12 deficiency who have not had pernicious anemia excluded as a cause.
  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: 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, unstable angina, coronary artery stent placement, angioplasty, or 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 ULN (including subjects on PPIs and H2 antagonists) at Screening.
  18. Blood creatinine exceeding ULN by more than 20% OR total albumin below the LLN by 10% (revised per Amendment 01).
  19. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels exceeding 2 times the ULN; total bilirubin exceeding 1.5 times the ULN.
  20. Participants with a history of cancer treatment with cytotoxic chemotherapy and/or radiotherapy.
  21. Participants with a history of ITP treatment with cytotoxic chemotherapy are still eligible for enrollment.
  22. Females who are pregnant (positive beta-human chorionic gonadotropin [B-hCG] test) or breastfeeding.
  23. Participants with a known allergy to E5501 or eltrombopag and any of their excipients.
  24. Participants with a history of significant aminotransferase elevations while receiving eltrombopag (defined as ALT and/or AST elevation >3 x ULN).
  25. Participants who are known nonresponders (defined as platelet counts that never exceed 50 x 10\^9/L) to all previous TPO agonist therapy (including previous E5501 therapy) who do not have a bone marrow examination consistent with ITP taken at any point after failure of TPO therapy to rule out MDS or other causes of thrombocytopenia.
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
24 participants (actual)

Study arms

  • 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, once daily and allow 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.

    Drug: Avatrombopag · Drug: Standard of care

  • Active comparator
    Eltrombopag (Core Study)

    Eltrombopag will be administered orally as 25 mg, 50 mg, or 75 mg in a flexible dose design for 26 weeks. Participants will receive blinded therapy at a starting dose of 50 mg eltrombopag once daily and allow to have their dose titrated up (maximum dose of 75 mg eltrombopag) or down (minimum dose of 25 mg eltrombopag) depending on their response to study drug.

    Drug: Eltrombopag · Drug: Standard of care

  • Experimental
    Avatrombopag (Open-label Extension)

    Participants who meet the eligibility requirements for the Open-label Extension (OLE) Phase or who discontinue the Core Study early because of lack of treatment effect will be eligible to continue into the OLE Phase for up to 104 weeks of open-label avatrombopag therapy. Participants who enter the OLE from the Core Study will receive a starting dose of open-label avatrombopag which will be determined by the last dose of study drug at the End of Treatment (EOT) Visit (Visit 22) of the Core Study. Participants who discontinue the Core Study early because of lack of treatment effect and enter the OLE will receive open-label avatrombopag at a starting dose of 20 mg once daily of open-label avatrombopag.

    Drug: Avatrombopag · Drug: Standard of care

Interventions

  • DrugEltrombopag

    Also known as: Promacta, Revolade

  • DrugAvatrombopag

    Also known as: E5501, Avatrombopag maleate

  • DrugStandard 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.

06

What researchers measure

Primary outcomes

  1. Change From Baseline in Local Platelet Count for the 6 Month Treatment Period

    Platelet responses to avatrombopag was evaluated using the platelet counts determined at local clinical laboratories. Only participants with non-missing data at both baseline and the relevant post-baseline visit are included in the change from baseline summary statistics. Standard deviation is not applicable for some of the categories, from Visit 14 to Visit 22, as the number of participants analyzed for that visit was 1 individual.

    Time frame: Day 5, Day 8, Week 2, Week 3, Week 4, Week 6, Week 8, Week 10, Week 12, Week 14, Week 16, Week 18, Week 19, Week 20, Week 22, Week 23, Week 24, Week 25, Week 26

07

Results

Posted Feb 6, 2018
Limitations and caveats
Study was terminated early (during the Extension Phase) due to significant enrollment changes.

Participant flow

Core Study
Participant flow — Core Study
MilestoneEltrombopag (Core Study)Avatrombopag (Core Study)Avatrombopag (Open-label Extension Phase)
Started11120
Completed010
Not completed11110
Withdrew: Adverse event, non-fatal010
Withdrew: Lack of efficacy510
Withdrew: Study terminated by sponsor690
Extension Phase
Participant flow — Extension Phase
MilestoneEltrombopag (Core Study)Avatrombopag (Core Study)Avatrombopag (Open-label Extension Phase)
Started006
Completed000
Not completed006
Withdrew: Adverse event, non-fatal001
Withdrew: Lack of efficacy001
Withdrew: Study terminated by sponsor004

Outcome measures

PrimaryChange From Baseline in Local Platelet Count for the 6 Month Treatment Period

Platelet responses to avatrombopag was evaluated using the platelet counts determined at local clinical laboratories. Only participants with non-missing data at both baseline and the relevant post-baseline visit are included in the change from baseline summary statistics. Standard deviation is not applicable for some of the categories, from Visit 14 to Visit 22, as the number of participants analyzed for that visit was 1 individual.

Time frame:
Day 5, Day 8, Week 2, Week 3, Week 4, Week 6, Week 8, Week 10, Week 12, Week 14, Week 16, Week 18, Week 19, Week 20, Week 22, Week 23, Week 24, Week 25, Week 26
Reported as:
Geometric mean · cells x 10^9/L
Change From Baseline in Local Platelet Count for the 6 Month Treatment Period
cells x 10^9/LEltrombopag (Core Study)Avatrombopag (Core Study)
Visit 3 (Day 5)8.60 ± 17.31212.85 ± 16.054
Visit 4 (Day 8)32.50 ± 44.51947.00 ± 59.690
Visit 5 (Week 2)73.41 ± 79.885171.71 ± 201.736
Visit 6 (Week 3)67.20 ± 95.536114.21 ± 117.172
Visit 7 (Week 4)28.72 ± 38.437108.79 ± 217.036
Visit 8 (Week 6)57.21 ± 57.718150.68 ± 134.902
Visit 9 (Week 8)67.25 ± 46.055121.31 ± 149.040
Visit 10 (Week 10)92.67 ± 34.649126.25 ± 90.602
Visit 11 (Week 12)87.33 ± 72.616185.10 ± 115.841
Visit 12 (Week 14 )104.33 ± 77.114159.38 ± 116.746
Visit 13 (Week 16)47.75 ± 2.475123.88 ± 124.474
Visit 14 (Week 18)107.50 ± NA46.50 ± 53.740
Visit 15 (Week 19)13.50 ± NA29.50 ± 22.627
Visit 16 (Week 20)—50.50 ± NA
Visit 18 (Week 22)—75.50 ± NA
Visit 19 (Week 23)—104.50 ± NA
Visit 20 (Week 24)—106.50 ± NA
Visit 21 (Week 25)—120.50 ± NA
Visit 22 (Week 26)—58.50 ± NA

Adverse events

Collected over Up to 34 Weeks in the Core Study (including Titration, Treatment, Dose Taper, and Follow-up for those that did not enter the Extension Phase) and up to 112 weeks in the Extension Phase (including Conversion, Maintenance, Dose Taper, and Follow-up).. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Eltrombopag (Core Study)—0/11 (0%)11/11 (100%)
Avatrombopag (Core Study)—2/12 (16.7%)11/12 (91.7%)
Avatrombopag (Extension Phase)—4/17 (23.5%)16/17 (94.1%)
Most frequent serious events
Most frequent serious events
EventEltrombopag (Core Study)Avatrombopag (Core Study)Avatrombopag (Extension Phase)
Idiopathic thrombocytopenic purpuraBlood and lymphatic system disorders0/111/121/17
Portal vein thrombosisHepatobiliary disorders0/111/121/17
Bronchitis MoraxellaInfections and infestations0/111/121/17
Thrombophlebitis SepticInfections and infestations0/111/121/17
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders0/111/121/17
PneumothoraxRespiratory, thoracic and mediastinal disorders0/111/121/17
InfluenzaInfections and infestations0/110/121/17
Chronic lymphotic leukaemiaNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/110/121/17
Most frequent other events
Showing 10 of 96
Most frequent other events
EventEltrombopag (Core Study)Avatrombopag (Core Study)Avatrombopag (Extension Phase)
FatigueGeneral disorders5/111/125/17
HeadacheNervous system disorders3/113/125/17
DiarrhoeaGastrointestinal disorders3/112/122/17
NasopharyngitisInfections and infestations3/112/124/17
NauseaGastrointestinal disorders2/113/123/17
Musculoskeletal painMusculoskeletal and connective tissue disorders0/113/123/17
DizzinessNervous system disorders2/113/124/17
InsomniaPsychiatric disorders1/113/124/17
ContusionInjury, poisoning and procedural complications2/110/121/17
ArthralgiaMusculoskeletal and connective tissue disorders2/111/122/17

Baseline characteristics

Safety analysis set included all participants who received at least one dose of study treatment and at least one postbaseline safety assessment.

Age, Continuous
Age, Continuous(Years)Eltrombopag (Core Study)Avatrombopag (Core Study)Total
Geometric mean45.4 ± 20.0950.8 ± 23.0448.2 ± 21.36
Sex: Female, Male
Sex: Female, Male(Participants)Eltrombopag (Core Study)Avatrombopag (Core Study)Total
Female7714
Male459
08

Study locations

1 site
  • Prairie Lakes Health Care System
    Watertown, South Dakota, United States
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Feb 6, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT01433978
Lead sponsor
Eisai Inc.
Responsible party
Sponsor
First posted
Sep 14, 2011
Start date
Mar 26, 2012
Primary completion
Sep 2013
Completion
Sep 2013
Results posted
Feb 6, 2018
Last update
Feb 6, 2018

Study contacts

Joe McIntosh
study director · Eisai Inc.

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
View the source record on ClinicalTrials.gov ↗

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