Hepatitis C MedDRA version: 16.1 Level: LLT Classification code 10047457 Term: Viral hepatitis C System Organ Class: 100000004862
Conditions
Interventions
Product Name: MK-5172
Product Code: MK-5172
Pharmaceutical Form: Tablet
INN or Proposed INN: MK-5172
CAS Number: 1350514-68-9
Other descriptive name: MK-5172
Concentration unit: mg milligram(s)
Concen
Sponsors
Merck Sharp & Dohme Corp.
Eligibility
Sex/Gender
All
Inclusion criteria
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 LLoQ after HCV RNA previously declined to or = to LLoQ after HCV RNA previously declined to <LLoQ. Occurred during the PR tail dosing period that followed a PR + DAA dosing period. -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 (LL
Exclusion criteria
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 1.7 HbA1c- >10% ALT ->10xULN AST- >10xULN (Read the rest in the protocol)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: In subjects with chronic HCV GT 1 infection who have failed prior DAA + PR treatment, with pre-treatment HCV RNA of at least 10,000 IU/mL: -To evaluate the efficacy of MK-5172 in combination with MK-8742 + R as assessed by the proportion of subjects achieving SVR12 (Sustained Virologic Response 12 weeks after the end of all study therapy), defined as HCV RNA <LLoQ (either TD[u] or TND) 12 weeks after the end of all study therapy. -To evaluate the safety and tolerability of MK-5172 in combination with MK-8742 + R.;Secondary Objective: -Evaluate efficacy of MK-5172 in combination with MK-8742 + R as assessed by proportion of subjects achieving SVR12 by prior DAA and prior DAA class, defined as HCV RNA <LLoQ (either TD[u] or TND) 12 weeks after end of study therapy -Evaluate emergence of RAVs to MK-5172 and MK-8742 when administered as part of a combination regimen + R by population sequencing and deep sequencing as applicable -Evaluate efficacy of MK-5172 in combination with MK-8742 + R as assessed by proportion of subjects achieving SVR24, defined as HCV RNA <LLoQ (either TD[u] or TND) 24 weeks after end of study therapy -Evaluate efficacy of MK-5172 in combination with MK-8742 + R as assessed by time to first achievement of undetectable (TND) HCV RNA (Read the rest in the protocol);Primary end point(s): Proportion of subjects achieving SVR12;Timepoint(s) of evaluation of this end point: SVR12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Week 2, 4, 12; SVR4, SVR12, SVR24;Secondary end point(s): -the proportion of subjects achieving SVR12 by prior DAA (i.e. boceprevir, telaprevir, simeprevir, sofosbuvir) and by prior DAA class -the emergence of antiviral resistance to MK-5172 and MK-8742 when administered as a combination regimen with R -the proportion of subjects achieving SVR24 and SVR4 -the time to first achievement of undetectable (TND) HCV RNA -the proportion of subjects achieving undetectable (TND) HCV RNA and HCV RNA < LLoQ at Week 2, Week 4, and Week 12 | — |
Countries
Austria, Israel, Italy, Spain, United States
Contacts
Public ContactInvestigación Clínica
Merck Sharp & Dohme de España S.A.
Outcome results
None listed