Chronic Hepatitis C Infected Patient MedDRA version: 19.0 Level: LLT Classification code 10019183 Term: HCV System Organ Class: 100000004848
Conditions
Interventions
Product Name: MK-3682B
Product Code: MK-3682B
Pharmaceutical Form: Tablet
INN or Proposed INN: MK-3682
Current Sponsor code: MK-3682
Other descriptive name: MK-3682
Concentration unit: mg milligra
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. be >or=18 years of age and >or= age of consent per local regulations on day of signing informed consent 2. HCV RNA (>or= 10,000 IU/mL in peripheral blood) at the time of screening 3. have documented chronic HCV GT5 or GT6 (with no evidence of non-typeable or mixed GT) infection and meet the definition below: - Positive for anti-HCV antibody, HCV RNA, or HCV GT5 or GT6 at least 6 months before Day 1, or - 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 4. be otherwise healthy as determined by the medical history, physical examination, ECG, and clinical laboratory measurements performed at the time of screening 5. have liver disease staging assessment as follows: 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 12.5 kPa - 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 × 100÷ (platelet count÷100) (APRI calculation to be provided by the central laboratory) NOTE: In the absence of a definitive diagnosis of presence or absence of cirrhosis by the above criteria, a liver biopsy or Fibroscan is required. Liver biopsy results supersede the results obtained by Fibroscan® or Fibrosure® 6. be HCV treatment naïve (defined as no prior exposure to any interferon, RBV, or other approved or experimental HCV-specific direct-acting antiviral agent) OR prior virologic failure after treatment with an interferon-containing regimen (comprised of interferon or pegylated interferon, with or without ribavirin) only. Subjects who were intolerant to an interferon-containing regimen will be allowed to enroll. Subjects may not have previously received treatment with HCV direct-acting antiviral agents 7. meet one of the following criteria: a. The subject is a male who is not of reproductive potential, defined as a male who has azoospermia (whether due to having had a vasectomy or due to an underlying medical condition) b. The subject is a female who is not of reproductive potential, defined as a female who either: (1) is postmenopausal (defined as at least 12 months with no menses in women >or=45 years of age); (2) has had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy, or bilateral tubal ligation/occlusion at least 6 weeks prior to screening; OR (3) has a congenital or acquired condition that prevents childbearing c. The subject is a female or a male who is of reproductive potential and agrees to avoid becoming pregnant or impregnating a partner beginning at least 2 weeks prior to administration of the initial dose of study drug through 14 days after taking the last dose of study drug (or longer if dictated by local regulations), by complying with one of the following: (1) practice abstinence† from heterosexu
Exclusion criteria
Exclusion criteria: 1. is under the age of legal consent, is mentally or legally incapacitated, has significant emotional problems at the time of pre-study screening visit or expected during the conduct of the study or has a history of a clinically significant psychiatric disorder which, in the opinion of the investigator, would interfere with the study procedures 2. 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 3. For cirrhotics: a. subjects that are Child-Pugh Class B or C, or who have a Pugh-Turcotte 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 4. is coinfected with hepatitis B virus (eg. HBsAg positive) 5. For subjects with HIV, has a history of opportunistic infection in the preceding 6 months prior to screening. A list of these events may be found in Appendix B of the following document: http://www.cdc.gov/mmwr/preview/mmwrhtml/00018871.htm 6. has a history of malignancy <or=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 7. has cirrhosis and liver imaging within 6 months of Day 1 showing evidence of hepatocellular carcinoma or is under evaluation for HCC NOTE If liver imaging within 6 months prior to Day 1 is not available, imaging is required during screening 8. 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 weeks after the study treatment period 9. is currently participating or has participated in a study with an investigational compound within 30 days of signing informed consent and is not willing to refrain from participating in another such study during the course of this study 10. Has, in the opinion of the investigator, clinically-relevant drug or alcohol abuse within 12 months of screening 11. is a female and is pregnant or breast-feeding, or expecting to conceive or donate eggs from at least 2 weeks prior to Day 1 through at least 14 days after the last dose of study drug, or longer if dictated by local regulations, OR is a male subject who is expecting to donate sperm or planning to impregnate female partner(s) from at least 2 weeks prior to Day 1 through 14 days after the last dose of study drug, or longer if dictated by local regulations NOTE After randomization, female subjects should avoid conceiving or donating eggs and male subjects should avoid impregnating a partner or donating sperm for at least 14 days after taking the last dose of study drug 12. 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 trial c. Subject with a history of gastric surgery (eg. stapling, bypass) or subject with a history of malabsorption disorders (eg. celiac sprue disease) d. Any clinically significant cardiac abnormalities/dysfunction that may interfere with subject treatment, assessment, or compliance with the protocol, including but not
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: MK-3682B (MK-3682 [225 mg] + GZR [50 mg] + MK-8408 [30 mg]) administered as two fixed-dose combination (FDC) tablets given once daily; Objectives will be evaluated separately for each HCV Genotype (GT) 1. To evaluate the efficacy of MK-3682B following 12 weeks of treatment as assessed by the proportion of subjects achieving SVR12 (defined as HCV 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 ;Secondary Objective: Objectives will be evaluated for each HCV GT 1. To evaluate the efficacy of MK-3682B following 8 weeks of treatment as assessed by the proportion of subjects achieving SVR12 (HCV RNA <LLOQ 12 weeks after the end of study therapy) 2. To evaluate the efficacy of 12 or 8 weeks of treatment with MK-3682B, respectively, as assessed by the proportion of subjects achieving SVR24 (HCV RNA <LLOQ 24 weeks after the end of study therapy) 3. To evaluate the efficacy of 12 or 8 weeks of treatment with MK-3682B, respectively, as assessed by the proportion of subjects experiencing virologic failure (either on-treatment failure or relapse post-treatment) at FW12 among subjects who do not discontinue the study for non-treatment-related reasons 4. To evaluate the effect of baseline resistance-associated polymorphisms in NS3, NS5A, and/or NS5B on the efficacy of 12 or 8 weeks of treatment with MK-3682B, respectively, as assessed by the proportion of subjects with baseline RAPs achieving SVR12 ;Primary end point(s): Proportion of subjects achieving SVR12;Timepoint(s) of evaluation of this end point: SVR12 (Sustained Virologic Response 12 weeks after the end of all study therapy). The subject has HCV RNA <LLOQ 12 weeks after the end of all study therapy | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Proportion of subjects achieving SVR24 Proportion of subjects experiencing virologic failure at Follow-up Week 12 among subjects who do not discontinue study for non-treatment-related reasons;Timepoint(s) of evaluation of this end point: SVR24 (Sustained Virologic Response 24 weeks after the end of all study therapy). The subject has HCV RNA <LLOQ 24 weeks after the end of all study therapy Virologic failure rate among subjects who do not discontinue the study for non-treatment-related reasons at FW12 | — |
Countries
Australia, Belgium, Canada, France, Hong Kong, South Africa, Thailand, United States
Contacts
Public ContactGlobal Clinical Trials Operations
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Outcome results
None listed