Treatment of hepatitis C virus (HCV) infection MedDRA version: 20.0 Level: LLT Classification code 10019752 Term: Hepatitis C virus (HCV) System Organ Class: 100000004848
Conditions
Interventions
Product Name: MK-3682B
Product Code: MK-3682B
Pharmaceutical Form: Tablet
INN or Proposed INN: GRAZOPREVIR
Current Sponsor code: MK-5172
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. The participant has HCV RNA (=10,000 IU/mL in peripheral blood) at the time of screening 2. The participant has documented chronic HCV GT3-infection (with no evidence of nontypeable or mixed GT) as follows: a) positive for anti-HCV antibody, HCV RNA, or HCV GT3 at least 6 months before Day 1, or b) positive for anti-HCV antibody or HCV RNA with a liver biopsy consistent with chronic HCV infection (such as the presence of fibrosis) before Day 1 3. The participant has liver disease staging assessment as follows: a) Absence of cirrhosis (F0 to F3) defined as any one of the following: i. a liver biopsy performed within 24 months of Day 1 showing absence of cirrhosis, or ii. FibroScan® performed within 12 months of Day 1 with a result =12.5 kPa,or iii. FibroSure® (FibroTest®) performed during Screening with a score of =0.48 and an aspartate aminotransferase to platelet ratio index (APRI) =1 b) Compensated Cirrhosis (F4) defined as any one of the following: i. a liver biopsy performed prior to Day 1 showing cirrhosis, or ii. FibroScan® performed within 12 months of Day 1 with a result >12.5 kPa, or iii. Fibroure® (FibroTest®) performed during Screening with a score of >0.75 and an APRI >2 4. The participant has an HCV treatment status that is 1 of the following: a) HCV TN (defined as no prior exposure to any IFN-containing regimen, RBV, or other approved or experimental HCV-specific DAA agent) b) HCV TE (defined as prior virologic failure after treatment with an IFN-containing regimen, with or without RBV, or intolerance to an IFN-containing regimen). Participants cannot have previously received treatment with HCV-specific DAA agents 5. The participant is male or female =18 years of age on day of signing informed consent 6. For female participants: - A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies : a) Not a woman of childbearing potential (WOCBP) OR b) A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 14 days after the last dose of study treatment 7. The participant provides written informed consent for the study 8. The participant has HIV infection documented at any time prior to screening by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV p24 antigen, or plasma HIV RNA VL 9. The participant meets 1 of the following criteria: a) not currently on ART and has no plans to initiate ART while participating in this study, must have CD4+ T-cell count >500 cells/mm3 at time of screening, or b) must have well-controlled HIV on ART, defined as all the following: i. CD4+T-cell count >200 cells/mm3 at time of screening ii. achieved and maintained virologic suppression (defined as confirmed HIV RNA level <LLOQ of available assay) for at least
Exclusion criteria
Exclusion criteria: 1. The participant 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 2. The participant is cirrhotic AND has a Child-Turcotte-Pugh score >6, corresponding to a Child Class B or C 3. The participant has cirrhosis AND liver imaging within 6 months of Day 1 showing evidence of HCC or is under evaluation for HCC 4. The participant is coinfected with HIV AND has a history of opportunistic infection in the preceding 6 months prior to screening 5. The participant 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 6. A WOCBP is expecting to conceive or donate eggs from Day 1 through at least 14 days after the last dose of study treatment or longer if dictated by local regulations 7. The participant has any of the following conditions: a. organ transplants (including hematopoietic stem cell transplants) other than cornea and hair b. poor venous access that precludes routine peripheral blood sampling required for this study c. history of gastric surgery (eg, stapling, bypass) or malabsorption disorders (eg, celiac sprue disease) d. any clinically significant cardiac abnormalities/dysfunction that may interfere with participant treatment, assessment, or compliance with the protocol, including but not limited to: unstable angina, unstable congestive heart failure, unstable arrhythmia; participants currently under evaluation for a potentially clinically significant cardiac abnormality/dysfunction are also excluded e. any major medical condition, clinically significant illness (other than HCV), pre-study laboratory or ECG abnormality, or history of any illness, which, in the opinion of the investigator, might interfere with participant treatment, assessment, compliance with the protocol, or confound the results of the study or pose additional risk in administering the study drug to the participant f. history of a medical/surgical condition that resulted in hospitalization within the 3 months prior to enrollment, other than for minor elective procedures g. medical /surgical conditions that may result in a need for hospitalization during the study duration h. any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids, tumor necrosis factor antagonists, or other immunosuppressant drugs through FW24 i. life-threatening serious adverse event (SAE) during the screening period j. evidence of history of chronic hepatitis not caused by HCV, including but not limited to, drug-induced hepatitis, hemochromatosis, Wilson’s disease, a1-antitrypsin deficiency, alcoholic liver disease, and autoimmune hepatitis 8. The participant is taking or plans to take any of the prohibited medications listed in the protocol or is taking herbal supplements, including but not limited to St. John’s Wort (Hypericum perforatum), from 2 weeks prior to Day 1 through 2 wee
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To evaluate the efficacy of MK-3682B as assessed by the proportion of participants in the immediate treatment group (ITG) achieving sustained virologic response (SVR) at 12 weeks post-treatment (SVR12) (defined as HCV ribonucleic acid [RNA] <lower limit of quantification [LLOQ] 12 weeks after the end of all study therapy). 2. To evaluate the safety and tolerability of MK-3682B in the ITG relative to the placebo treatment in the deferred treatment group (DTG) during the double-blind treatment period plus 14 days. ; Secondary Objective: 1. To evaluate the efficacy of MK-3682B as assessed by the proportion of participants in the ITG achieving SVR at 24 weeks post-treatment (SVR24) (defined as HCV RNA <LLOQ 24 weeks after the end of all study therapy). 2. To evaluate the efficacy of MK-3682B as assessed by the proportion of participants in the ITG experiencing virologic failure (either on-treatment failure or relapse post-treatment) through Follow-up Week (FW) 12 among participants who do not discontinue the study for non-treatment-related (eg, administrative) reasons. 3. To evaluate the effect of baseline resistance-associated substitutions (RASs) in nonstructural protein 3 (NS3), NS5A, and/or NS5B on the efficacy of MK-3682B, as assessed by the proportion of participants with baseline RASs achieving SVR12, within the ITG and the active treatment period in the DTG. ;Primary end point(s): Proportion of participants achieving Sustained virologic response 12 weeks post-treatment (SVR12) in the Immediate treatment group (ITG);Timepoint(s) of evaluation of this end point: Follow-up Week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Follow-up Week 12 and Follow-up Week 24; Secondary end point(s): 1. Proportion of participants achieving SVR24 in the ITG 2. Proportion of participants experiencing virologic failure through FW12 among all participants who do not discontinue study for non-treatment-related reasons in the ITG 3. Proportion of participants with baseline RASs achieving SVR12 in the ITG and the active treatment period in the Deferred treatment group (DTG) | — |
Countries
Australia, Canada, Denmark, France, Italy, Lithuania, Malaysia, New Zealand, Poland, Russian Federation, Thailand, United Kingdom, United States
Contacts
Public ContactClinical Trial Operations Depart.
UAB Merck Sharp & Dohme
Outcome results
None listed