A Phase II Clinical Trial to Study the Efficacy and Safety of the combination regimen of MK-5172 + MK-8742 + Ribavirin (R) in Subjects with Chronic Hepatitis C Virus Infectio

• Conditions: Hepatitis C; MedDRA version: 16.1Level: LLTClassification code 10047457Term: Viral hepatitis CSystem Organ Class: 100000004862; Therapeutic area: Diseases [C] - Virus Diseases [C02]

• Registration Number: EUCTR2013-004213-41-ES
• Lead Sponsor: Merck Sharp & Dohme Corp.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-04-01
• Last Update Posted: 10 July 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

1.be > or = to 18 years of age on day of signing informed consent.
2.HCV RNA ( > or = to 10,000 IU/mL in peripheral blood) at the time of screening
3.have documented chronic HCV GT1(with no evidence of non-typable or mixed genotype)infection:
-Positive for anti-HCV antibody, HCV RNA, or an HCV genotype at least 6 months before screening or
-Positive for anti-HCV antibody or HCV RNA at the time of screening with a liver biopsy consistent with chronic HCV infection (or a liver biopsy performed before enrollment with evidence of CHC disease, such as presence of fibrosis)
4.have liver disease staging assessment as follows:
Cirrhosis is defined as any one of the following [16,17]:
-A liver biopsy performed prior to Day 1 of this study showing cirrhosis (F4)
-Fibroscan performed within 12 calendar months of Day 1 of this study showing cirrhosis with result >12.5 kPa [17]*
-A FibroSure® (Fibrotest®)performed during Screening with a score of >0.75 and an aspartate aminotransferase (AST):platelet ratio index (APRI) of >2. APRI formula: AST÷lab upper limit of normal (ULN) for AST x 100÷{platelet count÷100} (APRI calculation to be provided by the central laboratory.)
Absence of cirrhosis is defined as any one of the following:
-Liver biopsy performed within 24 months of Day 1 of this study showing absence of cirrhosis
-Fibroscan performed within 12 months of Day 1 of this study with a result of < or = to 12.5 kPa[17]*
-A FibroSure® (Fibrotest®)score of < or = to 0.48 and Aspartate Aminotransferase to Platelet Ratio Index (APRI) of 1 during Screening
In the absence of a definitive diagnosis of presence or absence of cirrhosis by the above criteria, a liver biopsy is required. Liver biopsy results supersede the results obtained by Fibroscan or FibroSure®.
5.have received a prior regimen containing an approved DAA (boceprevir, telaprevir, simeprevir, or sofosbuvir) co-administered for at least 4 weeks with PR (note: due to the 4 week PR lead-in for boceprevir, a subject would meet this criterion after 8 weeks on this regimen). If prior to the approved DAA + PR containing regimen, the subject received a regimen only containing ribavirin and/or interferon(i.e., PR or interferon alone; unaccompanied by a DAA), this is also permitted.
Subjects HCV treatment history (i.e., type of therapy and duration of therapy) and reason for discontinuation of prior treatment (i.e., virologic failure, safety/tolerability, or administrative reasons) should be available.
Subjects that discontinued prior therapy due to virologic failure must have met one of the following definitions:
-PR+DAA Nonresponder: HCV RNA detected at end of treatment with a regimen that included one HCV DAA dosed in combination with PR. Subject must not have had undetectable HCV RNA during treatment. Can include subjects who met protocol-defined virologic futility rule (except for breakthrough, which is captured elsewhere).
-PR+DAA Breakthrough: Confirmed increase in HCV RNA > or = to LLoQ after HCV RNA previously declined to < LLOQ. Occurred during the DAA dosing period with a regimen that included one DAA dosed in combination with PR.
-PR+DAA Tail Breakthrough: Confirmed increase in HCV RNA > or = to LLoQ after HCV RNA previously declined to -PR+DAA Relapser: HCV RNA undetectable (TND) at end of treatment with a regimen that included oneDAA dosed in combination with PR, but HCV RNA quantifiable (

Exclusion Criteria

-has received any HCV regimen containing a DAA with the exception of boceprevir, telaprevir, simeprevir, or sofosbuvir in combination with PR.
Subjects who have been treated with one of these regimens more than once are excluded. Patients who have taken any DAAs in an interferonfree regimen are excluded.
-Has evidence of decompensated liver disease manifested by the presence of or history of ascites, esophageal or gastric variceal bleeding, hepatic encephalopathy or other signs or symptoms of advanced liver disease. For cirrhotics, subjects that are Child-Pugh Class B or C or who have a Child-Pugh-Turcotte (CPT) score >6, must be excluded.
NOTE: To calculate the Child-Pugh score, refer to the following website:
http://www.mdcalc.com/child-pugh-score-for-cirrhosis-mortality.
-is coinfected with hepatitis B virus (e.g., HBsAg positive) or HIV.
-has a history of malignancy ?5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer or carcinoma in situ; or is under evaluation for other active or suspected malignancy.
-Cirrhosis and liver imaging within 6 months of Day 1 showing evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC.
NOTE: If liver imaging within 6 months of Day 1 is not available, imaging is required during screening
-has clinically-relevant drug or alcohol abuse within 12 months of screening
-has any of the following conditions:
- Organ transplants (including hematopoietic stem cell transplants) other than cornea and hair.
-Poor venous access that precludes routine peripheral blood sampling required for this trial.
-Subject with a history of gastric surgery (e.g., stapling, bypass) or subject with a history of malabsorption disorders (e.g., celiac sprue disease).
-Any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids during the course of the trial.
-Hemoglobinopathy, including, but not limited to, thalassemia major
-has evidence or history of chronic hepatitis not caused by HCV, including but not limited to nonalcoholic steatohepatitis (NASH), druginduced hepatitis, and autoimmune hepatitis.
NOTE: Subjects with history of acute non-HCV-related hepatitis, which resolved > 6 months before study entry, can be enrolled.
-has exclusionary laboratory values as listed below:
NOTE: If any of the laboratory exclusion criteria below are met, the site may have the abnormal value retested one time.
Noncirrhotic/Cirrhotic Subjects
creatinine clearance <50 mL/min
haemoglobin < 12 g/dL for male, <11 g/dL for female subjects
Serum Albumin- < 3.0 g/dL (lower limit of normal) of laboratory reference range
INR - >1.7
HbA1c- >10%
ALT ->10xULN
AST- >10xULN
(Read the rest in the protocol)

Study & Design

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