Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT01355289
First received: May 16, 2011
Last updated: June 30, 2014
Last verified: June 2014
  Purpose

The study will have three phases: Prerandomization, Randomization (Core Study), and Extension. The Randomization Phase may include Treatment Periods A1 and A2 (depending when/if subjects enter the open-label extension, and a follow-up period (for those subjects not continuing into the open-label extension). The open-label extension may include Treatment Periods B1, B2, and B3 (depending on when subjects enter the open label extension), and a follow-up period. Subjects may be followed for sustained viral response, if appropriate. In the Core Study (randomization phase) subjects will be randomized (in a 1:1:1:1 ratio) to receive one of four treatments (placebo or E5501 [10mg, 20mg, and 30mg] for up to 21 days. Subjects will successfully complete Treatment Period A1 once their platelet counts are sufficient to enable initiation of antiviral treatment with PEG-IFN. The open label extension period will consist of up to three (depending on if/when subjects enter) Open-label Treatment Periods (B1, B2, and B3) and a follow-up period. During open-label treatment, all subjects will begin once-daily treatment with E5501 at a dose of 20 mg. In Treatment Periods B2 and B3, subjects will be allowed to have their E5501 dose titrated up or down in accordance with their individual response, within the range of a minimum of 5mg and a maximum of 50mg.


Condition Intervention Phase
Thrombocytopenia
Drug: E5501/Avatrombopag maleate
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • Proportion of responders [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
    A responder is defined as a subject having a platelet count of greater then or equal to 100x10^9/L by Day 21 starting from an average baseline platelet count of greater then or equal to 20x10^9/L to greater then or equal to 70x10


Enrollment: 65
Study Start Date: November 2011
Study Completion Date: May 2014
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: E5501/Avatrombopag maleate - 10 mg; 20 mg; 30 mg Drug: E5501/Avatrombopag maleate

All subjects will initiate open-label, once-daily treatment with E5501 at a dose of 20 mg.

After Treatment Period B1, E5501 will be administered in a flexible-dose design. During Treatment Periods B2 and B3, the E5501 dose may be titrated up or down in accordance with their individual response, within the range of a minimum of 5 mg and a maximum of 50 mg.

Active Comparator: 10mg E5501/Avatrombopag maleate Drug: E5501/Avatrombopag maleate

All subjects will initiate open-label, once-daily treatment with E5501 at a dose of 20 mg.

After Treatment Period B1, E5501 will be administered in a flexible-dose design. During Treatment Periods B2 and B3, the E5501 dose may be titrated up or down in accordance with their individual response, within the range of a minimum of 5 mg and a maximum of 50 mg.

Active Comparator: 20mg E5501/Avatrombopag maleate Drug: E5501/Avatrombopag maleate

All subjects will initiate open-label, once-daily treatment with E5501 at a dose of 20 mg.

After Treatment Period B1, E5501 will be administered in a flexible-dose design. During Treatment Periods B2 and B3, the E5501 dose may be titrated up or down in accordance with their individual response, within the range of a minimum of 5 mg and a maximum of 50 mg.

Active Comparator: 30mg E5501/Avatrombopag maleate Drug: E5501/Avatrombopag maleate

All subjects will initiate open-label, once-daily treatment with E5501 at a dose of 20 mg.

After Treatment Period B1, E5501 will be administered in a flexible-dose design. During Treatment Periods B2 and B3, the E5501 dose may be titrated up or down in accordance with their individual response, within the range of a minimum of 5 mg and a maximum of 50 mg.


  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males or females greater then or equal to 18 years of age
  • 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
  • Subjects with chronic HCV-related thrombocytopenia (defined as a platelet count greater then or equal to 20x10^9/L to 70x10^9/L) who require antiviral treatment
  • Chronic HCV infection (defined as the presence of anti-HCV antibodies and detectable serum HCV RNA levels)
  • Model for End-stage Liver disease score greater then or equal to 24
  • Adequate renal function as evidenced by a calculated creatinine clearance greater then or equal to 50mL/minute per the Cockcroft and Gault formula
  • Life expectancy greater then 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 thromboses (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 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 >21 units (168 g) [male] and >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 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 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)

Exclusion Criteria:

  • History of arterial or venous thrombosis, including any thrombosis (partial or complete) in the main portal vein and portal vein branches, and thrombosis of any part of the splenic-mesenteric system
  • Any evidence of current PVT as detected by Doppler sonography or appropriate MRI-CT as Screening and/or within approximately 30 days prior to screening
  • Evidence of myocardial infarction in the last 6 months or uncompensated congestive heart failure
  • Co-infection with human immunodeficiency virus (HIV) or hepatitis B or acute hepatitis C
  • Any prohibited concomitant medications or therapy that cannot be discontinued by Visit 1
  • Weekly alcohol intake greater then 21 units (168g) [male] and greater then 14 units (112g) [female]
  • Any known medical condition, other then chronic liver disease, that can lead to thrombocytopenia
  • History of hepatocellular carcinoma, metastatic liver cancer, or liver transplantation
  • History of immune thrombocytopenic purpura (ITP)
  • History of myelodysplastic syndrome
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01355289

Locations
United States, California
Health Care Consultants
Los Angeles, California, United States
United States, Virginia
Metropolitan Research
Fairfax, Virginia, United States, 22031
Sponsors and Collaborators
Eisai Inc.
Investigators
Study Director: Alireza Manhuchehri Eisai Inc.
  More Information

No publications provided

Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT01355289     History of Changes
Other Study ID Numbers: E5501-G000-203, 2010-024479-20
Study First Received: May 16, 2011
Last Updated: June 30, 2014
Health Authority: European Union: European Medicines Agency
United States: Food and Drug Administration

Keywords provided by Eisai Inc.:
Chronic Hepatitis C related

Additional relevant MeSH terms:
Hepatitis
Hepatitis C
Hepatitis C, Chronic
Hepatitis, Chronic
Thrombocytopenia
Blood Platelet Disorders
Digestive System Diseases
Flaviviridae Infections
Hematologic Diseases
Hepatitis, Viral, Human
Liver Diseases
RNA Virus Infections
Virus Diseases

ClinicalTrials.gov processed this record on November 27, 2014