Chronic Hepatitis C Virus Related Thrombocytopenia to Evaluate the Effects of E5501 (Study E5501-G000-203 AM02)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT01355289
First received: May 16, 2011
Last updated: April 8, 2014
Last verified: April 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 (Pegylated interferon). 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: No ]
    A responder is defined as a subject having a platelet count of >= 100 x 109/L by Day 21 starting from an average baseline platelet count of >= 20 x 109/L to >= 70 x 109/L.


Enrollment: 65
Study Start Date: November 2011
Estimated Study Completion Date: April 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 (Hepatitis C Virus)-related thrombocytopenia (defined as a platelet count greater than or equal to 20 x 109/L to 70 x 109/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; Child-Pugh score greater than or equal to 6
  • Adequate renal function as evidenced by a calculated creatinine clearance greater then or equal to 50 mL/minute per the Cockcroft and Gault formula
  • Life expectancy greater then or equal to 3 months

Exclusion Criteria:

  • 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
  • Any evidence of current DVT (deep vein thrombosis) as detected by Doppler sonography and portal vein flow rate < 15 cm/second at Screening or within 30 days prior to Screening (revised per Amendment 02)
  • Any known family history of hereditary thrombophilic disorders (e.g., Factor V Leiden, antithrombin III deficiency)
  • Evidence of myocardial infarction in the last 6 months or uncompensated congestive heart failure (New York Heart Association Class III or IV)
  • 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, 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)
  • Weekly alcohol intake > 21 units (168 g) [male] and >14 units (112 g) [female]
  • Any known medical condition, other than chronic liver disease, that can lead to thrombocytopenia
  • History of hepatocellular carcinoma, metastatic liver cancer, or liver transplantation (revised per Amendment 01) (revised per Amendment 02)
  • History of ITP (Idiopathic thrombocytopenic purpura)
  • History of myelodysplastic syndrome
  • 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)
  • 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
  • Subjects with a history of suicide attempts
  • Subjects with a history of hospitalization for depression within the past 5 years
  • Subjects with any current severe or poorly controlled psychiatric or seizure disorder
  • Current use of recreational drugs
  • Subjects who have participated in another investigational study within 30 days prior to Visit 1
  • Subjects with hypersensitivity, intolerance, or allergy to E5501 or any anti-HCV therapies or their ingredients
  • 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
  • Scheduled for surgery during the projected course of the study
  • Subjects who have any medical conditions or diseases that would contraindicate treatment with anti-HCV therapy (added per Amendment 01)
  • Subjects who are currently treated with PPIs (Proton-pump inhibitors) or H2 (Histamine-2 receptor) antagonists 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)
  • 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)
  • Subjects with a history of gastric atrophy (added per Amendment 02)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01355289

Locations
United States, California
Coronado, California, United States
Los Angeles, California, United States
San Francisco, California, United States
United States, Louisiana
New Orleans, Louisiana, United States
United States, Massachusetts
Boston, Massachusetts, United States
United States, North Carolina
Asheville, North Carolina, United States
United States, Texas
Dallas, Texas, United States
Houston, Texas, United States
Bulgaria
Sofia, Bulgaria
Varna, Bulgaria
France
Lyon Cedex 04, France
Paris, France
Germany
Hamburg, Germany
Hannover, Germany
Heidelberg, Germany
Israel
Haifa, Israel
Jerusalem, Israel
Nazareth, Israel
Tel Aviv, Israel
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
Study First Received: May 16, 2011
Last Updated: April 8, 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 A
Hepatitis, Chronic
Hepatitis C
Thrombocytopenia
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Blood Platelet Disorders
Hematologic Diseases
Maleic acid
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014