A Study on the Effect of E5501 (study drug) in Subjects with Chronic Hepatitis C Virus (HCV)-related Thrombocytopenia who are Potential Candidates for Antiviral Treatment

• Conditions: Thrombocytopenia associated with chronic hepatitis C virus; MedDRA version: 16.1Level: HLGTClassification code 10035534Term: Platelet disordersSystem Organ Class: 10005329 - Blood and lymphatic system disorders; MedDRA version: 16.1Level: PTClassification code 10043554Term: ThrombocytopeniaSystem Organ Class: 10005329 - Blood and lymphatic system disorders; MedDRA version: 16.1Level: SOCClassification code 10005329Term: Blood and lymphatic system disordersSystem Organ Class: 10005329 - Blood and lymphatic system disorders; MedDRA version: 16.1Level: LLTClassification code 10039884Term: Secondary thrombocytopeniaSystem Organ Class: 10005329 - Blood and lymphatic system disorders; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2010-024479-20-DE
• Lead Sponsor: Eisai Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-08-31
• Last Update Posted: 5 August 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 52

Inclusion Criteria

Core Study (Part A) Entry Criteria (for Double-blind Treatment Periods)
• Males or females = 18 years of age
• Subjects with chronic HCV-related thrombocytopenia (defined as a platelet count = 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 (MELD) score = 20,Child-Pugh Score = 6
• Adequate renal function as evidenced by a calculated creatinine clearance = 50 mL/minute per the Cockcroft and Gault formula
• Life expectancy = 3 months
• Females must not be pregnant at Screening or Baseline (as documented by a negative serum beta-human chorionic gonadotropin [ß-hCG] test with a minimum sensitivity 25 IU/L or equivalent units of ß-hCG). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.
• All females will be considered to be of childbearing potential unless they are postmenopausal (at least 12 months consecutive amenorrhea, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (i.e., bilateral tubal ligation, hysterectomy, or bilateral oophorectomy, all with surgery
at least 1 month before dosing).
• Females of childbearing potential must not have had unprotected sexual intercourse within 30 days before study entry and must agree to use a highly effective method of contraception (e.g., abstinence, an intrauterine device, a double-barrier method such as condom + spermicide or condom + diaphragm with spermicide, a progesterone-only contraceptive implant/injection, or have a vasectomized partner
with confirmed azoospermia) throughout the entire study period and for 30 days after study drug discontinuation. If currently abstinent, the subject must agree to use a double-barrier method as described above if they become sexually active during the study period or for 30 days after study drug discontinuation. All women who are of reproductive potential and who have been using estrogen-containing oral contraceptives must have discontinued the contraceptive product for at least 30 days before dosing, throughout the entire study period, and for 30 days after study drug discontinuation. All female subjects of childbearing potential who receive ribavirin (antiviral treatment) must agree to use one of the aforementioned methods for 6 months (4 months for subjects enrolled in Israel or the European Union [EU])
(added per Amendment 01) after antiviral treatment discontinuation.
• Male subjects must either have had a successful vasectomy (confirmed azoospermia) or they and their female partner meet the criteria above (not of childbearing potential or practicing highly effective contraception throughout the study period and for 30 days after study drug discontinuation or 6 months [7 months for subjects enrolled in Israel or the EU] (added per Amendment 01) after antiviral treatment
discontinuation). In addition, sperm donation cannot take place for 7 months after discontinuation of antiviral treatment.
• Provision of written informed consent
• Are willing and able to comply with all aspects of the protocol

Entry Criteria for Treatment Periods A2, B1 B2 or B 3.
- subjects who achieve sufficient increase in platelet counts (=100 x 109/L)
Open-label Extension (Part B)

Treatment Period B1
• Subjects who fail to obtain a sufficient increase in platelet co

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 PVT as detected by Doppler sonography and portal vein flow rate < 15 cm/ second at screening or within 30 days prior to screening
• 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 may affect platelet count within 1 week prior to screening
• 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, or currently on a waiting list for liver transplantation
• History of ITP
• History of myelodysplastic syndrome
• History of pernicious anemia or subjects with vitamin B12 deficiency (defined as less than the lower limit of normal) who have not had pernicious anemia excluded as cause
• 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 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
• 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
• Fasting gastrin-17 blood levels exceeding 1.5 times the upper limit of normal (ULN) (including subjects on PPIs and H2 antagonists) at screening
• Subjects with a history of gastric atrophy

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified