Chronic Hepatitis C Virus Related Thrombocytopenia to Evaluate the Effects of E5501

January 25, 2018 updated by: Eisai Inc.

A Phase II, Randomized, Multicenter, Placebo-Controlled, Double-Blind, Parallel-Group Study, With an Open-Label Extension, to Evaluate the Efficacy, Safety, and Pharmacokinetics of E5501 in Subjects With Chronic Hepatitis C Virus Related Thrombocytopenia Who Are Potential Candidates for Antiviral Treatment

To evaluate the efficacy of E5501 by measuring platelet response in subjects with chronic hepatitis C virus (HCV)-related thrombocytopenia who require antiviral treatment.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This study had three phases: Prerandomization (Screening), Randomization (Core Study), and Open-Label Extension (OLE). The Randomization Phase included Treatment Periods A1 and A2 and a Follow-up Period (for those participants not continuing into the OLE phase). The OLE Phase included Treatment Periods B1, B2, and B3 (depending on when a participant entered the OLE), and a Follow-up Period. Participants may have been followed for sustained viral response, if appropriate. In the Core Study (randomization phase) participants were randomized (in a 1:1:1:1 ratio) to receive one of four treatments (placebo or avatrombopag [10mg, 20mg, and 30mg] for up to 21 days. Participants who successfully completed Treatment Period A1, (platelet count >=100x10^9/L) initiated antiviral treatment with pegylated interferon (PEG-IFN) alpha-2a and progressed to Treatment Period A2. Participants with a platelet count >=150x10^9/L initiated antiviral treatment and progressed into Treatment Period B2, study drug was interrupted then eventually restarted at 10 mg daily once their platelet counts returned to acceptable levels. Those who were not considered successful after 21 days in Treatment Phase A1 were withdrawn from the Core Study (Part A) and were eligible to enter the OLE at Treatment Period B1. Participants who chose to not enter the OLE entered into the Follow-up Phase. At the end of Treatment Period A2, eligible participants could enter the OLE at Treatment Period B3. In the OLE Phase, participants entering into Open-label Treatment Period B1 began once-daily treatment with avatrombopag at a dose of 20 mg without titration for up to 21 days. Once the participant's platelet counts were sufficient, they entered Treatment Period B2. Participant's eligible to enter into Treatment Period B2 received avatrombopag and antiviral treatment for 13 weeks. Participants who successfully completed Treatment Period A2 or B2 could continue on antiviral treatment for up to a maximum of 48 weeks (including the 13 weeks in Treatment Periods A2 or B2) and open-label avatrombopag, at the investigator's discretion. In Treatment Period B3, the dose of avatrombopag was allowed to be titrated up or down in accordance with the participant's platelet count response, within the range of a minimum of 5 mg and a maximum of 50 mg. In the Follow-up Period, participants were seen at either a single 30-day follow-up visit or followed for the full 30 days after the last dose of avatrombopag.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
65

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States
        • Health Care Consultants
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Metropolitan Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Males or females greater than or equal to 18 years of age
  2. Women of childbearing potential must agree to use a highly effective method of contraception for at least one menstrual cycle prior to starting study drug, throughout the entire study period, and for 30 days after the last dose of study drug
  3. Subjects with chronic HCV-related thrombocytopenia (defined as a platelet count greater than or equal to 20x10^9/L to 70x10^9/L) who require antiviral treatment
  4. Chronic HCV infection (defined as the presence of anti-HCV antibodies and detectable serum HCV RNA levels)
  5. Model for End-stage Liver disease score greater than or equal to 24
  6. Adequate renal function as evidenced by a calculated creatinine clearance greater than or equal to 50 mL/minute per the Cockcroft and Gault formula
  7. Life expectancy greater than or equal to 3 months

Exclusion Criteria: Subjects who meet any of the following criteria will be excluded from participation in the study:

  1. Any history of arterial or venous thrombosis, including partial or complete thrombosis (e.g., stroke, transient ischemic attack, myocardial infarction, deep vein thrombosis or pulmonary embolism), thrombosis (partial or complete) in the main portal vein and portal vein branches, and thrombosis of any part of the splenic-mesenteric system
  2. Any evidence of current portal vein thrombosis (PVT) as detected by Doppler sonography and portal vein flow rate less than 15 cm/second at Screening or within 30 days prior to Screening (revised per Amendment 02)
  3. Any known family history of hereditary thrombophilic disorders (e.g., Factor V Leiden, antithrombin III deficiency)
  4. Evidence of myocardial infarction in the last 6 months or uncompensated congestive heart failure (New York Heart Association Class III or IV)
  5. Co-infection with human immunodeficiency virus (HIV) or hepatitis B or acute hepatitis C
  6. Any prohibited concomitant medications or therapy that cannot be discontinued by Visit 1, e.g., subjects currently receiving interferon who cannot undergo a 4-week washout period prior to Screening, or subjects who receive blood products that affect platelet count within 1 week prior to Screening (revised per Amendment 02)
  7. Weekly alcohol intake greater than 21 units (168 g) [male] and greater than 14 units (112 g) [female]
  8. Any known medical condition, other than chronic liver disease, that can lead to thrombocytopenia
  9. History of hepatocellular carcinoma, metastatic liver cancer, or liver transplantation (revised per Amendment 01) (revised per Amendment 02)
  10. History of idiopathic thrombocytopenic Purpura (ITP)
  11. History of myelodysplastic syndrome
  12. History of pernicious anemia or subjects with vitamin B12 deficiency (defined as less than the lower limit of normal [LLN]) who have not had pernicious anemia excluded as a cause (Added per Amendment 02)
  13. Evidence of clinically significant disease (e.g., cardiac, respiratory, gastrointestinal, renal disease) that, in the opinion of the investigator, could affect the subject's safety or study conduct
  14. Subjects with a history of suicide attempts
  15. Subjects with a history of hospitalization for depression within the past 5 years
  16. Subjects with any current severe or poorly controlled psychiatric or seizure disorder
  17. Current use of recreational drugs
  18. Subjects who have participated in another investigational study within 30 days prior to Visit 1
  19. Subjects with hypersensitivity, intolerance, or allergy to E5501 or any anti-HCV therapies or their ingredients
  20. Any past or current (revised per Amendment 01) medical condition that, in the opinion of the investigator, would compromise the subject's ability to safely complete the study
  21. Scheduled for surgery during the projected course of the study
  22. Subjects who have any medical conditions or diseases that would contraindicate treatment with anti-HCV therapy (added per Amendment 01)
  23. Subjects who are currently treated with proton pump inhibitors (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 (added per Amendment 01)
  24. Fasting gastrin-17 blood levels exceeding 1.5 times the upper limit of normal (ULN) at Screening (including subjects on PPIs or H2 antagonists) (revised per Amendment 02)
  25. Subjects with a history of gastric atrophy (added per Amendment 02)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
PLACEBO_COMPARATOR: Placebo (Core Study)
Placebo, will be administered orally, once daily for up to 21 days.
Drug: Placebo
ACTIVE_COMPARATOR: Avatrombopag 10 mg (Core Study)
Avatrombopag 10 mg, will be administered orally, once daily, preferably with food for up to 21 days.
Drug: Avatrombopag
Other Names:
  • E5501
  • Avatrombopag maleate
ACTIVE_COMPARATOR: Avatrombopag 20 mg (Core Study)
Avatrombopag 20 mg, will be administered orally, once daily, preferably with food for up to 21 days.
Drug: Avatrombopag
Other Names:
  • E5501
  • Avatrombopag maleate
Drug: Pegylated interferon (PEG-IFN)
Participants in Treatment Periods A2, B2, and B3 are to receive antiviral treatment PEG-IFN, ribavirin, or telaprevir. Provided by the sponsor.
Drug: Telaprevir
Participants in Treatment Periods A2, B2, and B3 are to receive antiviral treatment PEG-IFN, ribavirin, or telaprevir. Provided by the sponsor
Other Names:
  • Incivek
  • Incivo
Drug: Ribavirin
Participants in Treatment Periods A2, B2, and B3 are to receive antiviral treatment PEG-IFN, ribavirin, or telaprevir. Provided by the sponsor
Other Names:
  • Copegus
  • Rebetol
  • Virazole
  • Ribasphere
  • Moderiba dose pack
  • Moderiba
ACTIVE_COMPARATOR: Avatrombopag 30 mg (Core Study)
Avatrombopag 30 mg, will be administered orally, once daily, preferably with food for up to 21 days.
Drug: Avatrombopag
Other Names:
  • E5501
  • Avatrombopag maleate
EXPERIMENTAL: Avatrombopag (Open-Label Extension)
Avatrombopag will be initiated at a dose of 20 mg, once daily in the open-label extension (OLE) period. The avatrombopag dose will be titrated up or down in accordance with the participant's individual response, within the range of a minimum of 5 mg and a maximum of 50 mg for up to 48 weeks.
Drug: Avatrombopag
Other Names:
  • E5501
  • Avatrombopag maleate
Drug: Pegylated interferon (PEG-IFN)
Participants in Treatment Periods A2, B2, and B3 are to receive antiviral treatment PEG-IFN, ribavirin, or telaprevir. Provided by the sponsor.
Drug: Telaprevir
Participants in Treatment Periods A2, B2, and B3 are to receive antiviral treatment PEG-IFN, ribavirin, or telaprevir. Provided by the sponsor
Other Names:
  • Incivek
  • Incivo
Drug: Ribavirin
Participants in Treatment Periods A2, B2, and B3 are to receive antiviral treatment PEG-IFN, ribavirin, or telaprevir. Provided by the sponsor
Other Names:
  • Copegus
  • Rebetol
  • Virazole
  • Ribasphere
  • Moderiba dose pack
  • Moderiba

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants Who Achieved Platelet Response (Greater Than or Equal to 100 x 10^9/L) by Day 21 of Treatment Period A1 of Core Study
Time Frame: Baseline to Day 21
A responder was defined as a participant having a platelet count of greater than or equal to 100x10^9/L by Day 21 starting from an average baseline platelet count of greater than 20 x 10^9/L to less than or equal to 70 x 10^9/L.
Baseline to Day 21

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change From Baseline of Local Platelet Count by Visit During Treatment Period A1 of Core Study
Time Frame: Day 7 and Day 14
Missing platelet counts were imputed using last observation carried forward (LOCF) approach for subjects who achieved platelet response at prior visits.
Day 7 and Day 14
Number of Participants Who Achieved Platelet Count Greater Than 30 X 10^9/L From Baseline to Day 21 During Treatment Period A1 of Core Study
Time Frame: Baseline to Day 21
Blood draws were taken to monitor platelet counts.
Baseline to Day 21
Number of Participants Who Initiated Antiviral Treatment by Day 21 of Period A1 of Core Study
Time Frame: Baseline to Day 21
Blood draws were taken to monitor platelet counts during the first 21 days of study treatment. When a platelet count of greater than or equal to 100 X 10^9/L was attained, antiviral treatment was initiated.
Baseline to Day 21

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Eisai Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Alireza Manhuchehri, Eisai Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2011

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2014

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 1, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 16, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 17, 2011

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 18, 2011

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 22, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 25, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • E5501-G000-203

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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