Hepatitis C
Conditions
Brief summary
This is a randomized, three-part, parallel-group, open-label trial of grazoprevir (MK-5172) (100 mg) and uprifosbuvir (MK-3682) (300 mg or 450 mg) with either elbasvir (MK-8742) (50 mg) or ruzasvir (MK-8408) (60 mg), and with or without ribavirin (RBV), in treatment-naive (TN) or treatment-experienced (TE) cirrhotic (C) or non-cirrhotic (NC) participants infected with hepatitis C virus (HCV) genotype (GT) 3, GT4, GT5, or GT6. Part A will consist of 4 arms to evaluate the safety of dose combinations. In Part B, participants will take 2 uprifosbuvir (+) grazoprevir (+) ruzasvir (MK-3682B) fixed dose combination (FDC) tablets once daily (q.d.) by mouth, with or without twice-daily (b.i.d.) RBV (200 mg capsules; weight-based dosing). Participants who relapse following completion of therapy in Part A will be offered the option of retreatment with 16 weeks of uprifosbuvir (+) grazoprevir (+) ruzasvir with RBV in Part C (data obtained from Part C will not be used in the analysis of outcome measures).
Detailed description
In Part A, study therapy will be administered as separate products, each taken q.d. by mouth. In Part B and Part C, participants will take 2 uprifosbuvir (+) grazoprevir (+) ruzasvir FDC tablets q.d. by mouth; each uprifosbuvir (+) grazoprevir (+) ruzasvir FDC tablet contains grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg.
Interventions
DRUGGrazoprevir
Part A: one grazoprevir 100 mg tablet taken q.d. by mouth.
DRUGUprifosbuvir
Part A: two or three uprifosbuvir 150 mg (300 or 450 mg total daily dose) tablets taken q.d. by mouth.
DRUGElbasvir
Part A: one elbasvir 50 mg tablet taken q.d. by mouth.
DRUGRuzasvir
Part A: six ruzasvir 10 mg (60 mg total daily dose) capsules taken q.d. by mouth.
DRUGMK-3682B
Part B and Part C: two FDC tablets, each containing grazoprevir 50 mg + elbasvir 225 mg + ruzasvir 30 mg, taken q.d. by mouth.
DRUGRibavirin (RBV)
Part B and Part C: RBV 200 mg capsules taken b.i.d. by mouth at a total daily dose of 800 mg - 1400 mg based on participant body weight.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has documented chronic HCV GT3, GT4, GT5, or GT6 with no evidence of non-typeable or mixed GT infection * Is otherwise healthy as determined by the medical history, physical examination, electrocardiogram (ECG), and clinical laboratory measurements performed at the time of screening * Has cirrhosis of the liver (Part B only) or is non-cirrhotic (Part A and B) * Is HCV treatment-naïve or has experienced virologic failure after completing a prior Pegylated Interferon/Ribavirin (Peg-IFN/RBV) regimen * Is of non childbearing potential or agrees to avoid becoming pregnant or impregnating a partner beginning at least 2 weeks prior to administration of the initial dose of study drug and for 14 days after the last dose of study drug if not taking RBV, or for 6 months after the last dose of study drug if taking RBV (or longer if dictated by local regulations). If not abstinent from heterosexual activity, participants in Part A must use 2 acceptable forms of barrier contraception whereas participants in Parts B and C must use 2 acceptable forms of contraception which may include oral contraceptives Part B only: * If coinfected with human immunodeficiency virus (HIV) is not currently on antiretroviral therapy (ART) and has no plans to initiate ART treatment while participating in this study OR has well-controlled HIV on ART. * Has at least 1 viable antiretroviral regimen alternative beyond their current regimen in the event of HIV virologic failure and the development of anti-retroviral drug resistance.
Exclusion criteria
Parts A, B, and C (unless otherwise specified): * 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. * If cirrhotic (Part B only), is Child-Pugh Class B or C or has a Pugh-Turcotte (CPT) score \>5. * Is coinfected with hepatitis B virus (Parts A, B, and C) or is coinfected with HIV (Part A only; HIV coinfected participants are eligible for Parts B and C). * If coinfected with HIV, has a history of opportunistic infection in the preceding 6 months prior to screening. * 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. * Has cirrhosis and liver imaging within 6 months of Day 1 showing evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC. * Has clinically-relevant drug or alcohol abuse within 12 months of screening. * Is female and is pregnant or breastfeeding, or expecting to conceive or donate eggs from at least 2 weeks prior to Day 1 and 6 months after the last dose of study medication, or longer if dictated by local regulations OR a male participant who is expecting to donate sperm from at least 2 weeks prior to day 1 until 6 months after the last dose of study medication. * 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. * History of gastric surgery (e.g., stapling, bypass) or a history of malabsorption disorders (e.g., celiac sprue disease). * Current or history of any clinically significant cardiac abnormalities/dysfunction, including but not limited to: angina, congestive heart failure, myocardial infarction, pulmonary hypertension, complex congenital heart disease, cardiomyopathy, significant arrhythmia, uncontrolled hypertension, a history of use of antianginal or anti-arrythmic agents for cardiac conditions, prolonged ECG QTc interval (\>470 ms for males or \>480 ms for females by either the Fridericia formula) at the screening visit, personal or family history of Torsade de pointes. * Chronic pulmonary disease, including but not limited to: clinically significant chronic obstructive pulmonary disease, interstitial lung disease, pulmonary fibrosis, sarcoidosis. * Central nervous system (CNS) trauma requiring intubation, intracranial pressure monitoring, brain meningeal or skull surgery, or resulting in seizure, coma, permanent neurologic deficits, abnormal brain imaging, or cerebral spinal fluid (CSF) leak. Prior brain hemorrhage and/or intracranial aneurysms (whether adequately repaired or not). * Current or history of seizure disorder unless seizure was \>10 years ago, a single isolated event, no history of or current use of anti-seizure medications prescribed, and a normal neurological examination is documented in trial files within 6 months of Day 1. * Has a history of stroke or transient ischemic attack. * Has a history of a medical/surgical condition that resulted in hospitalization within the 3 months prior to enrollment, other than for minor elective procedures. * Has medical/surgical conditions that may result in a need for hospitalization during the period of the study. * Has any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids, tumor necrosis factor (TNF) antagonists, or other immunosuppressant drugs during the course of the trial. * Has any condition, prestudy laboratory or ECG abnormality or history of any illness, which, in the opinion of the investigator, might confound the results of the study or pose additional risk in administering the study drugs to the participant. * Has had a life-threatening serious adverse event (SAE) during the screening period. * Has evidence of history of chronic hepatitis not caused by HCV, including but not limited to nonalcoholic steatohepatitis (NASH), drug-induced hepatitis, hemochromatosis, Wilson's disease, α1-antitrypsin deficiency, alcoholic liver disease and autoimmune hepatitis Parts B and C only: is a male whose female partner(s) is/are pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of HCV GT3-infected Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12) | Up to 20 weeks (Part A), up to 28 weeks (Part B) | SVR12 is defined as HCV ribonucleic acid (RNA) less than the lower limit of quantification (\<LLOQ, 15 IU/mL) 12 weeks after the end of all study therapy. A4+B4: GT3 NC TN MK-3682B (8 weeks) arm includes both participants from Part A and Part B who received equivalent dose of MK-3682B. |
| Number of Participants Experiencing an Adverse Event (AE) | Up to 40 weeks | An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. Part C in the table below combines all (eight) participants from the four distinct arms of Part A who relapsed and were subsequently treated with MK-3682B + RBV for 16 weeks. |
| Number of Participants Who Had Study Drug Discontinued Due to an AE | Up to 16 weeks | An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. Part C in the table below combines all (eight) participants from the four distinct arms of Part A who relapsed and were subsequently treated with MK-3682B + RBV for 16 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of GT3-infected Participants Achieving SVR at Follow-up Week 24 (SVR24) | Up to 40 weeks | SVR24 is defined as HCV RNA \<LLOQ of 15 IU/mL 24 weeks after the end of all study therapy. A4+B4: GT3 NC TN MK-3682B (8 weeks) arm includes both participants from Part A and Part B who received equivalent dose of MK-3682B. |
Participant flow
Recruitment details
No participants were randomized to the 'B21: GT5 NC TN MK-3682B (12 weeks)' arm.
Pre-assignment details
Participants were enrolled into either Part A or Part B. Part A enrolled non-cirrhotic (NC), treatment-naïve (TN) participants with hepatitis C virus (HCV) genotype (GT) 3; Part B enrolled NC or cirrhotic (C), TN or treatment-experienced (TE) participants with HCV GT3, GT4, GT5 or GT6. Participants who relapsed in Part A were retreated in Part C.
Participants by arm
| Arm | Count |
|---|---|
| A1: GT3 NC TN Grazoprevir+Uprifosbuvir+Elbasvir (8 Weeks) In Part A, HCV GT3-infected NC TN participants received grazoprevir (100 mg) + uprifosbuvir (300 mg) + elbasvir (50 mg) q.d. by mouth for 8 weeks. Part A participants who relapsed following completion of therapy were offered the option of retreatment with 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. and RBV (weight-based dosing) b.i.d. by mouth for 16 weeks during Part C. | 21 |
| A2: GT3 NC TN Grazoprevir+Uprifosbuvir+Ruzasvir (8 Weeks) In Part A, HCV GT3-infected NC TN participants received grazoprevir (100 mg) + uprifosbuvir (300 mg) + ruzasvir (60 mg) q.d. by mouth for 8 weeks. Part A participants who relapsed following completion of therapy were offered the option of retreatment with 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. and RBV (weight-based dosing) b.i.d. by mouth for 16 weeks during Part C. | 21 |
| A3: GT3 NC TN Grazoprevir+Uprifosbuvir+Elbasvir (8 Weeks) In Part A, HCV GT3-infected NC TN participants received grazoprevir (100 mg) + uprifosbuvir (450 mg) + elbasvir (50 mg) q.d. by mouth for 8 weeks. Part A participants who relapsed following completion of therapy were offered the option of retreatment with 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. and RBV (weight-based dosing) b.i.d. by mouth for 16 weeks during Part C. | 22 |
| A4: GT3 NC TN Grazoprevir+Uprifosbuvir+Ruzasvir (8 Weeks) In Part A, HCV GT3-infected NC TN participants received grazoprevir 100 mg + uprifosbuvir 450 mg + ruzasvir 60 mg q.d. by mouth for 8 weeks. Part A participants who relapsed following completion of therapy received retreatment with 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. and RBV (weight-based dosing) b.i.d. by mouth for 16 weeks during Part C. | 22 |
| B4: GT3 NC TN MK-3682B (8 Weeks) In Part B, HCV GT3-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 8 weeks. | 16 |
| B5: GT3 NC TN MK-3682B + RBV (8 Weeks) In Part B, HCV GT3-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 8 weeks. | 36 |
| B6: GT3 NC TN MK-3682B (12 Weeks) In Part B, HCV GT3-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks. | 37 |
| B7: GT3 NC TN MK-3682B + RBV (12 Weeks) In Part B, HCV GT3-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 12 weeks. | 35 |
| B8: GT3 NC TE MK-3682B (8 Weeks) In Part B, HCV GT3-infected NC TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 8 weeks. | 15 |
| B9: GT3 NC TE MK-3682B + RBV (8 Weeks) In Part B, HCV GT3-infected NC TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 8 weeks. | 14 |
| B10: GT3 NC TE MK-3682B (12 Weeks) In Part B, HCV GT3-infected NC TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks. | 14 |
| B11: GT3 NC TE MK-3682B + RBV (12 Weeks) In Part B, HCV GT3-infected NC TE participants received 2 MK-3682 FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 12 weeks. | 15 |
| B12: GT3 NC TE MK-3682B (16 Weeks) In Part B, HCV GT3-infected NC TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 16 weeks. | 16 |
| B13: GT3 C TN MK-3682B (12 Weeks) In Part B, HCV GT3-infected C TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks. | 13 |
| B14: GT3 C TN MK-3682B + RBV (12 Weeks) In Part B, HCV GT3-infected C TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 12 weeks. | 16 |
| B15: GT3 C TN MK-3682B (16 Weeks) In Part B, HCV GT3-infected C TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 16 weeks. | 14 |
| B16: GT3 C TE MK-3682B (12 Weeks) In Part B, HCV GT3-infected C TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks. | 15 |
| B17: GT3 C TE MK-3682B + RBV (12 Weeks) In Part B, HCV GT3-infected C TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 12 weeks. | 14 |
| B18: GT3 C TE MK-3682B (16 Weeks) In Part B, HCV GT3-infected C TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 16 weeks. | 20 |
| B19: GT3 C TE MK-3682B + RBV (16 Weeks) In Part B, HCV GT3-infected C TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 16 weeks | 25 |
| B20: GT4 NC TN MK-3682B (8 Weeks) In Part B, HCV GT4-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 8 weeks. | 7 |
| B21: GT5 NC TN MK-3682B (12 Weeks) In Part B, HCV GT5-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks. | 0 |
| B22: GT6 NC TN MK-3682B (12 Weeks) In Part B, HCV GT6-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks. | 4 |
| Total | 412 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 | FG016 | FG017 | FG018 | FG019 | FG020 | FG021 | FG022 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part A and Part B | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Part A and Part B | Lost to Follow-up | 1 | 0 | 0 | 0 | 0 | 2 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part A and Part B | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Part A and Part B | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | A1: GT3 NC TN Grazoprevir+Uprifosbuvir+Elbasvir (8 Weeks) | Total | B22: GT6 NC TN MK-3682B (12 Weeks) | B20: GT4 NC TN MK-3682B (8 Weeks) | B19: GT3 C TE MK-3682B + RBV (16 Weeks) | B18: GT3 C TE MK-3682B (16 Weeks) | B17: GT3 C TE MK-3682B + RBV (12 Weeks) | B16: GT3 C TE MK-3682B (12 Weeks) | B15: GT3 C TN MK-3682B (16 Weeks) | B14: GT3 C TN MK-3682B + RBV (12 Weeks) | B13: GT3 C TN MK-3682B (12 Weeks) | B12: GT3 NC TE MK-3682B (16 Weeks) | B11: GT3 NC TE MK-3682B + RBV (12 Weeks) | B10: GT3 NC TE MK-3682B (12 Weeks) | B9: GT3 NC TE MK-3682B + RBV (8 Weeks) | B8: GT3 NC TE MK-3682B (8 Weeks) | B7: GT3 NC TN MK-3682B + RBV (12 Weeks) | B6: GT3 NC TN MK-3682B (12 Weeks) | B5: GT3 NC TN MK-3682B + RBV (8 Weeks) | B4: GT3 NC TN MK-3682B (8 Weeks) | A4: GT3 NC TN Grazoprevir+Uprifosbuvir+Ruzasvir (8 Weeks) | A3: GT3 NC TN Grazoprevir+Uprifosbuvir+Elbasvir (8 Weeks) | A2: GT3 NC TN Grazoprevir+Uprifosbuvir+Ruzasvir (8 Weeks) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized 18 to 35 years | 4 Participants | 49 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 7 Participants | 9 Participants | 8 Participants | 3 Participants | 4 Participants | 3 Participants | 4 Participants |
| Age, Customized 36 to 50 years | 12 Participants | 150 Participants | 1 Participants | 3 Participants | 6 Participants | 6 Participants | 3 Participants | 4 Participants | 3 Participants | 3 Participants | 7 Participants | 6 Participants | 4 Participants | 6 Participants | 5 Participants | 5 Participants | 12 Participants | 14 Participants | 11 Participants | 4 Participants | 12 Participants | 14 Participants | 9 Participants |
| Age, Customized 51 to 64 years | 5 Participants | 194 Participants | 3 Participants | 3 Participants | 18 Participants | 13 Participants | 9 Participants | 11 Participants | 9 Participants | 13 Participants | 4 Participants | 9 Participants | 9 Participants | 6 Participants | 7 Participants | 8 Participants | 16 Participants | 13 Participants | 16 Participants | 6 Participants | 3 Participants | 5 Participants | 8 Participants |
| Age, Customized Less than 18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Over 64 years | 0 Participants | 19 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants | 3 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 9 Participants | 179 Participants | 2 Participants | 1 Participants | 5 Participants | 2 Participants | 1 Participants | 8 Participants | 3 Participants | 5 Participants | 3 Participants | 5 Participants | 6 Participants | 8 Participants | 2 Participants | 7 Participants | 23 Participants | 23 Participants | 19 Participants | 7 Participants | 11 Participants | 14 Participants | 15 Participants |
| Sex: Female, Male Male | 12 Participants | 233 Participants | 2 Participants | 6 Participants | 20 Participants | 18 Participants | 13 Participants | 7 Participants | 11 Participants | 11 Participants | 10 Participants | 11 Participants | 9 Participants | 6 Participants | 12 Participants | 8 Participants | 12 Participants | 14 Participants | 17 Participants | 9 Participants | 11 Participants | 8 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk | EG019 affected / at risk | EG020 affected / at risk | EG021 affected / at risk | EG022 affected / at risk | EG023 affected / at risk | EG024 affected / at risk | EG025 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 19 | 0 / 2 | 0 / 20 | 0 / 1 | 0 / 19 | 0 / 3 | 0 / 20 | 0 / 2 | 0 / 16 | 0 / 36 | 0 / 37 | 0 / 35 | 0 / 15 | 0 / 14 | 0 / 14 | 0 / 15 | 0 / 16 | 0 / 13 | 0 / 16 | 0 / 14 | 0 / 15 | 0 / 14 | 0 / 20 | 0 / 25 | 0 / 7 | 0 / 4 |
| other Total, other adverse events | 17 / 19 | 1 / 2 | 12 / 20 | 1 / 1 | 13 / 19 | 3 / 3 | 16 / 20 | 2 / 2 | 9 / 16 | 30 / 36 | 24 / 37 | 32 / 35 | 12 / 15 | 12 / 14 | 9 / 14 | 13 / 15 | 13 / 16 | 9 / 13 | 14 / 16 | 12 / 14 | 12 / 15 | 11 / 14 | 15 / 20 | 21 / 25 | 3 / 7 | 3 / 4 |
| serious Total, serious adverse events | 1 / 19 | 0 / 2 | 0 / 20 | 0 / 1 | 1 / 19 | 0 / 3 | 0 / 20 | 1 / 2 | 0 / 16 | 1 / 36 | 0 / 37 | 1 / 35 | 0 / 15 | 0 / 14 | 0 / 14 | 0 / 15 | 1 / 16 | 1 / 13 | 0 / 16 | 2 / 14 | 2 / 15 | 2 / 14 | 2 / 20 | 1 / 25 | 0 / 7 | 0 / 4 |
Outcome results
Primary
Number of Participants Experiencing an Adverse Event (AE)
An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. Part C in the table below combines all (eight) participants from the four distinct arms of Part A who relapsed and were subsequently treated with MK-3682B + RBV for 16 weeks.
Time frame: Up to 40 weeks
Population: All participants who received at least 1 dose of study drug, categorized according to the treatment actually received. A4+B4 arm includes both participants from Part A and Part B who received equivalent dose of MK-3682B. Part C arm includes participants who relapsed following the completion of Part A therapy and received treatment during Part C.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| A1: GT3 NC TN Grazoprevir+Uprifosbuvir+Elbasvir (8 Weeks) | Number of Participants Experiencing an Adverse Event (AE) | 18 Participants |
| A2: GT3 NC TN Grazoprevir+Uprifosbuvir+Ruzasvir (8 Weeks) | Number of Participants Experiencing an Adverse Event (AE) | 14 Participants |
| A3: GT3 NC TN Grazoprevir+Uprifosbuvir+Elbasvir (8 Weeks) | Number of Participants Experiencing an Adverse Event (AE) | 16 Participants |
| A4: GT3 NC TN Grazoprevir+Uprifosbuvir+Ruzasvir (8 Weeks) | Number of Participants Experiencing an Adverse Event (AE) | 17 Participants |
| A4+B4: GT3 NC TN MK-3682B (8 Weeks) | Number of Participants Experiencing an Adverse Event (AE) | 26 Participants |
| B4: GT3 NC TN MK-3682B (8 Weeks) | Number of Participants Experiencing an Adverse Event (AE) | 9 Participants |
| B5: GT3 NC TN MK-3682B + RBV (8 Weeks) | Number of Participants Experiencing an Adverse Event (AE) | 30 Participants |
| B6: GT3 NC TN MK-3682B (12 Weeks) | Number of Participants Experiencing an Adverse Event (AE) | 25 Participants |
| B7: GT3 NC TN MK-3682B + RBV (12 Weeks) | Number of Participants Experiencing an Adverse Event (AE) | 33 Participants |
| B8: GT3 NC TE MK-3682B (8 Weeks) | Number of Participants Experiencing an Adverse Event (AE) | 12 Participants |
| B9: GT3 NC TE MK-3682B + RBV (8 Weeks) | Number of Participants Experiencing an Adverse Event (AE) | 12 Participants |
| B10: GT3 NC TE MK-3682B (12 Weeks) | Number of Participants Experiencing an Adverse Event (AE) | 9 Participants |
| B11: GT3 NC TE MK-3682B + RBV (12 Weeks) | Number of Participants Experiencing an Adverse Event (AE) | 13 Participants |
| B12: GT3 NC TE MK-3682B (16 Weeks) | Number of Participants Experiencing an Adverse Event (AE) | 13 Participants |
| B13: GT3 C TN MK-3682B (12 Weeks) | Number of Participants Experiencing an Adverse Event (AE) | 9 Participants |
| B14: GT3 C TN MK-3682B + RBV (12 Weeks) | Number of Participants Experiencing an Adverse Event (AE) | 14 Participants |
| B15: GT3 C TN MK-3682B (16 Weeks) | Number of Participants Experiencing an Adverse Event (AE) | 12 Participants |
| B16: GT3 C TE MK-3682B (12 Weeks) | Number of Participants Experiencing an Adverse Event (AE) | 12 Participants |
| B17: GT3 C TE MK-3682B + RBV (12 Weeks) | Number of Participants Experiencing an Adverse Event (AE) | 12 Participants |
| B18: GT3 C TE MK-3682B (16 Weeks) | Number of Participants Experiencing an Adverse Event (AE) | 16 Participants |
| B19: GT3 C TE MK-3682B + RBV (16 Weeks) | Number of Participants Experiencing an Adverse Event (AE) | 21 Participants |
| B20: GT4 NC TN MK-3682B (8 Weeks) | Number of Participants Experiencing an Adverse Event (AE) | 3 Participants |
| B22: GT6 NC TN MK-3682B (12 Weeks) | Number of Participants Experiencing an Adverse Event (AE) | 3 Participants |
| Part C: GT3 NC TN: MK-3682B + RBV (16 Weeks) | Number of Participants Experiencing an Adverse Event (AE) | 7 Participants |
Primary
Number of Participants Who Had Study Drug Discontinued Due to an AE
An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. Part C in the table below combines all (eight) participants from the four distinct arms of Part A who relapsed and were subsequently treated with MK-3682B + RBV for 16 weeks.
Time frame: Up to 16 weeks
Population: All participants who received at least 1 dose of study drug, categorized according to the treatment actually received. A4+B4 arm includes both participants from Part A and Part B who received equivalent dose of MK-3682B. Part C arm includes participants who relapsed following the completion of Part A therapy and received treatment during Part C.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| A1: GT3 NC TN Grazoprevir+Uprifosbuvir+Elbasvir (8 Weeks) | Number of Participants Who Had Study Drug Discontinued Due to an AE | 0 Participants |
| A2: GT3 NC TN Grazoprevir+Uprifosbuvir+Ruzasvir (8 Weeks) | Number of Participants Who Had Study Drug Discontinued Due to an AE | 0 Participants |
| A3: GT3 NC TN Grazoprevir+Uprifosbuvir+Elbasvir (8 Weeks) | Number of Participants Who Had Study Drug Discontinued Due to an AE | 0 Participants |
| A4: GT3 NC TN Grazoprevir+Uprifosbuvir+Ruzasvir (8 Weeks) | Number of Participants Who Had Study Drug Discontinued Due to an AE | 0 Participants |
| A4+B4: GT3 NC TN MK-3682B (8 Weeks) | Number of Participants Who Had Study Drug Discontinued Due to an AE | 0 Participants |
| B4: GT3 NC TN MK-3682B (8 Weeks) | Number of Participants Who Had Study Drug Discontinued Due to an AE | 0 Participants |
| B5: GT3 NC TN MK-3682B + RBV (8 Weeks) | Number of Participants Who Had Study Drug Discontinued Due to an AE | 0 Participants |
| B6: GT3 NC TN MK-3682B (12 Weeks) | Number of Participants Who Had Study Drug Discontinued Due to an AE | 0 Participants |
| B7: GT3 NC TN MK-3682B + RBV (12 Weeks) | Number of Participants Who Had Study Drug Discontinued Due to an AE | 1 Participants |
| B8: GT3 NC TE MK-3682B (8 Weeks) | Number of Participants Who Had Study Drug Discontinued Due to an AE | 0 Participants |
| B9: GT3 NC TE MK-3682B + RBV (8 Weeks) | Number of Participants Who Had Study Drug Discontinued Due to an AE | 0 Participants |
| B10: GT3 NC TE MK-3682B (12 Weeks) | Number of Participants Who Had Study Drug Discontinued Due to an AE | 0 Participants |
| B11: GT3 NC TE MK-3682B + RBV (12 Weeks) | Number of Participants Who Had Study Drug Discontinued Due to an AE | 0 Participants |
| B12: GT3 NC TE MK-3682B (16 Weeks) | Number of Participants Who Had Study Drug Discontinued Due to an AE | 0 Participants |
| B13: GT3 C TN MK-3682B (12 Weeks) | Number of Participants Who Had Study Drug Discontinued Due to an AE | 0 Participants |
| B14: GT3 C TN MK-3682B + RBV (12 Weeks) | Number of Participants Who Had Study Drug Discontinued Due to an AE | 1 Participants |
| B15: GT3 C TN MK-3682B (16 Weeks) | Number of Participants Who Had Study Drug Discontinued Due to an AE | 1 Participants |
| B16: GT3 C TE MK-3682B (12 Weeks) | Number of Participants Who Had Study Drug Discontinued Due to an AE | 0 Participants |
| B17: GT3 C TE MK-3682B + RBV (12 Weeks) | Number of Participants Who Had Study Drug Discontinued Due to an AE | 0 Participants |
| B18: GT3 C TE MK-3682B (16 Weeks) | Number of Participants Who Had Study Drug Discontinued Due to an AE | 1 Participants |
| B19: GT3 C TE MK-3682B + RBV (16 Weeks) | Number of Participants Who Had Study Drug Discontinued Due to an AE | 0 Participants |
| B20: GT4 NC TN MK-3682B (8 Weeks) | Number of Participants Who Had Study Drug Discontinued Due to an AE | 0 Participants |
| B22: GT6 NC TN MK-3682B (12 Weeks) | Number of Participants Who Had Study Drug Discontinued Due to an AE | 0 Participants |
| Part C: GT3 NC TN: MK-3682B + RBV (16 Weeks) | Number of Participants Who Had Study Drug Discontinued Due to an AE | 0 Participants |
Primary
Percentage of HCV GT3-infected Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12)
SVR12 is defined as HCV ribonucleic acid (RNA) less than the lower limit of quantification (\<LLOQ, 15 IU/mL) 12 weeks after the end of all study therapy. A4+B4: GT3 NC TN MK-3682B (8 weeks) arm includes both participants from Part A and Part B who received equivalent dose of MK-3682B.
Time frame: Up to 20 weeks (Part A), up to 28 weeks (Part B)
Population: Analysis population included HCV GT3 participants who received treatment and did not have major protocol deviations that may substantially affect the results of the SVR endpoints. Therefore, only GT3 treatment arms are presented in the table below.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A1: GT3 NC TN Grazoprevir+Uprifosbuvir+Elbasvir (8 Weeks) | Percentage of HCV GT3-infected Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12) | 90.5 Percentage of participants |
| A2: GT3 NC TN Grazoprevir+Uprifosbuvir+Ruzasvir (8 Weeks) | Percentage of HCV GT3-infected Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12) | 95.2 Percentage of participants |
| A3: GT3 NC TN Grazoprevir+Uprifosbuvir+Elbasvir (8 Weeks) | Percentage of HCV GT3-infected Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12) | 86.4 Percentage of participants |
| A4: GT3 NC TN Grazoprevir+Uprifosbuvir+Ruzasvir (8 Weeks) | Percentage of HCV GT3-infected Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12) | 90.9 Percentage of participants |
| A4+B4: GT3 NC TN MK-3682B (8 Weeks) | Percentage of HCV GT3-infected Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12) | 92.1 Percentage of participants |
| B4: GT3 NC TN MK-3682B (8 Weeks) | Percentage of HCV GT3-infected Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12) | 93.8 Percentage of participants |
| B5: GT3 NC TN MK-3682B + RBV (8 Weeks) | Percentage of HCV GT3-infected Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12) | 100.0 Percentage of participants |
| B6: GT3 NC TN MK-3682B (12 Weeks) | Percentage of HCV GT3-infected Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12) | 97.2 Percentage of participants |
| B7: GT3 NC TN MK-3682B + RBV (12 Weeks) | Percentage of HCV GT3-infected Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12) | 100.0 Percentage of participants |
| B8: GT3 NC TE MK-3682B (8 Weeks) | Percentage of HCV GT3-infected Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12) | 100.0 Percentage of participants |
| B9: GT3 NC TE MK-3682B + RBV (8 Weeks) | Percentage of HCV GT3-infected Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12) | 92.9 Percentage of participants |
| B10: GT3 NC TE MK-3682B (12 Weeks) | Percentage of HCV GT3-infected Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12) | 100.0 Percentage of participants |
| B11: GT3 NC TE MK-3682B + RBV (12 Weeks) | Percentage of HCV GT3-infected Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12) | 93.3 Percentage of participants |
| B12: GT3 NC TE MK-3682B (16 Weeks) | Percentage of HCV GT3-infected Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12) | 93.8 Percentage of participants |
| B13: GT3 C TN MK-3682B (12 Weeks) | Percentage of HCV GT3-infected Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12) | 92.3 Percentage of participants |
| B14: GT3 C TN MK-3682B + RBV (12 Weeks) | Percentage of HCV GT3-infected Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12) | 100.0 Percentage of participants |
| B15: GT3 C TN MK-3682B (16 Weeks) | Percentage of HCV GT3-infected Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12) | 100.0 Percentage of participants |
| B16: GT3 C TE MK-3682B (12 Weeks) | Percentage of HCV GT3-infected Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12) | 100.0 Percentage of participants |
| B17: GT3 C TE MK-3682B + RBV (12 Weeks) | Percentage of HCV GT3-infected Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12) | 100.0 Percentage of participants |
| B18: GT3 C TE MK-3682B (16 Weeks) | Percentage of HCV GT3-infected Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12) | 100.0 Percentage of participants |
| B19: GT3 C TE MK-3682B + RBV (16 Weeks) | Percentage of HCV GT3-infected Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12) | 96.0 Percentage of participants |
Secondary
Percentage of GT3-infected Participants Achieving SVR at Follow-up Week 24 (SVR24)
SVR24 is defined as HCV RNA \<LLOQ of 15 IU/mL 24 weeks after the end of all study therapy. A4+B4: GT3 NC TN MK-3682B (8 weeks) arm includes both participants from Part A and Part B who received equivalent dose of MK-3682B.
Time frame: Up to 40 weeks
Population: Analysis population included HCV GT3 participants who received treatment and did not have major protocol deviations that may substantially affect the results of the SVR endpoints. Therefore, only GT3 treatment arms are presented in the table below.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A1: GT3 NC TN Grazoprevir+Uprifosbuvir+Elbasvir (8 Weeks) | Percentage of GT3-infected Participants Achieving SVR at Follow-up Week 24 (SVR24) | 90.0 Percentage of participants |
| A2: GT3 NC TN Grazoprevir+Uprifosbuvir+Ruzasvir (8 Weeks) | Percentage of GT3-infected Participants Achieving SVR at Follow-up Week 24 (SVR24) | 95.2 Percentage of participants |
| A3: GT3 NC TN Grazoprevir+Uprifosbuvir+Elbasvir (8 Weeks) | Percentage of GT3-infected Participants Achieving SVR at Follow-up Week 24 (SVR24) | 86.4 Percentage of participants |
| A4: GT3 NC TN Grazoprevir+Uprifosbuvir+Ruzasvir (8 Weeks) | Percentage of GT3-infected Participants Achieving SVR at Follow-up Week 24 (SVR24) | 90.9 Percentage of participants |
| A4+B4: GT3 NC TN MK-3682B (8 Weeks) | Percentage of GT3-infected Participants Achieving SVR at Follow-up Week 24 (SVR24) | 92.1 Percentage of participants |
| B4: GT3 NC TN MK-3682B (8 Weeks) | Percentage of GT3-infected Participants Achieving SVR at Follow-up Week 24 (SVR24) | 93.8 Percentage of participants |
| B5: GT3 NC TN MK-3682B + RBV (8 Weeks) | Percentage of GT3-infected Participants Achieving SVR at Follow-up Week 24 (SVR24) | 100.0 Percentage of participants |
| B6: GT3 NC TN MK-3682B (12 Weeks) | Percentage of GT3-infected Participants Achieving SVR at Follow-up Week 24 (SVR24) | 97.2 Percentage of participants |
| B7: GT3 NC TN MK-3682B + RBV (12 Weeks) | Percentage of GT3-infected Participants Achieving SVR at Follow-up Week 24 (SVR24) | 100.0 Percentage of participants |
| B8: GT3 NC TE MK-3682B (8 Weeks) | Percentage of GT3-infected Participants Achieving SVR at Follow-up Week 24 (SVR24) | 100.0 Percentage of participants |
| B9: GT3 NC TE MK-3682B + RBV (8 Weeks) | Percentage of GT3-infected Participants Achieving SVR at Follow-up Week 24 (SVR24) | 92.9 Percentage of participants |
| B10: GT3 NC TE MK-3682B (12 Weeks) | Percentage of GT3-infected Participants Achieving SVR at Follow-up Week 24 (SVR24) | 100.0 Percentage of participants |
| B11: GT3 NC TE MK-3682B + RBV (12 Weeks) | Percentage of GT3-infected Participants Achieving SVR at Follow-up Week 24 (SVR24) | 93.3 Percentage of participants |
| B12: GT3 NC TE MK-3682B (16 Weeks) | Percentage of GT3-infected Participants Achieving SVR at Follow-up Week 24 (SVR24) | 93.8 Percentage of participants |
| B13: GT3 C TN MK-3682B (12 Weeks) | Percentage of GT3-infected Participants Achieving SVR at Follow-up Week 24 (SVR24) | 92.3 Percentage of participants |
| B14: GT3 C TN MK-3682B + RBV (12 Weeks) | Percentage of GT3-infected Participants Achieving SVR at Follow-up Week 24 (SVR24) | 100.0 Percentage of participants |
| B15: GT3 C TN MK-3682B (16 Weeks) | Percentage of GT3-infected Participants Achieving SVR at Follow-up Week 24 (SVR24) | 100.0 Percentage of participants |
| B16: GT3 C TE MK-3682B (12 Weeks) | Percentage of GT3-infected Participants Achieving SVR at Follow-up Week 24 (SVR24) | 100.0 Percentage of participants |
| B17: GT3 C TE MK-3682B + RBV (12 Weeks) | Percentage of GT3-infected Participants Achieving SVR at Follow-up Week 24 (SVR24) | 100.0 Percentage of participants |
| B18: GT3 C TE MK-3682B (16 Weeks) | Percentage of GT3-infected Participants Achieving SVR at Follow-up Week 24 (SVR24) | 100.0 Percentage of participants |
| B19: GT3 C TE MK-3682B + RBV (16 Weeks) | Percentage of GT3-infected Participants Achieving SVR at Follow-up Week 24 (SVR24) | 96.0 Percentage of participants |