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)

NCT01433978 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: E5501-G000-305
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Idiopathic Thrombocytopenic Purpura

Outcome Measures

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.

  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

Study Arms (3)

Avatrombopag (Core Study)

ACTIVE COMPARATOR

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

Eltrombopag (Core Study)

ACTIVE COMPARATOR

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

Avatrombopag (Open-label Extension)

EXPERIMENTAL

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

Eltrombopag DRUG

Also known as: Promacta, Revolade

Eltrombopag (Core Study)

Avatrombopag DRUG

Also known as: E5501, Avatrombopag maleate

Avatrombopag (Core Study); Avatrombopag (Open-label Extension)

Standard of care DRUG

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.

Avatrombopag (Core Study); Avatrombopag (Open-label Extension); Eltrombopag (Core Study)

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women greater than or equal to 18 years of age.
• 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.
• Participants who previously received one or more ITP therapies (including, but not limited to corticosteroids, immunoglobulins, azathioprine, danazol, cyclophosphamide and/or rituximab).
• 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.
• 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.

You may not qualify if:

• Core Study
• 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 \[SLE\]).
• Participants considered unable, or unwilling to comply with the study protocol requirements or give informed consent, as determined by the investigator.
• 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).
• History of MDS.
• History of pernicious anemia or participants with vitamin B12 deficiency who have not had pernicious anemia excluded as a cause.
• 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.
• 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).
• Participants with a history of cirrhosis, portal hypertension, and chronic active hepatitis.
• Participants with concurrent malignant disease.
• Use of immunoglobulins (IVIg and anti-D) within 1 week of randomization.
• Splenectomy or use of rituximab within 12 weeks of randomization.
• Use of romiplostim or eltrombopag within 4 weeks of randomization.
• 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.
• 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.

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (1)

Prairie Lakes Health Care System

Watertown, South Dakota, United States

Location

MeSH Terms

Conditions

Purpura, Thrombocytopenic, Idiopathic

Interventions

eltrombopag; avatrombopag; Standard of Care

Condition Hierarchy (Ancestors)

Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia; Hemorrhagic Disorders; Autoimmune Diseases; Immune System Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Limitations and Caveats

Study was terminated early (during the Extension Phase) due to significant enrollment changes.

Results Point of Contact

• Title: Eisai Inc.
• Organization: Eisai Call Center

888-422-4743

Study Officials

• Joe McIntosh

  Eisai Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2011
• First Posted: September 14, 2011
• Study Start: March 26, 2012
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2013
• Last Updated: February 6, 2018
• Results First Posted: February 6, 2018

Record last verified: 2018-01

Locations

US (1)