Hepatitis C
Conditions
Brief summary
This is a study of the safety and efficacy of grazoprevir (MK-5172) in combination with elbasvir (MK-8742) ± ribavirin (RBV). The primary efficacy endpoint will be Sustained Virologic Response 12 weeks after the end of all study therapy (SVR12) in each of the treatment arms.
Detailed description
Part A is being done in treatment-naïve (TN), genotype 1 (GT1), interferon eligible, non-cirrhotic (N-C) participants with chronic hepatitis C (CHC). Participants will be assigned randomly to 1 of 2 treatment arms in which they will receive grazoprevir 100 mg once daily (QD) + elbasvir 20 mg or 50 mg QD and twice daily (BID) RBV, or to a treatment arm in which they will receive grazoprevir 100 mg QD + elbasvir 50 mg QD without RBV. Treatment will last 12 weeks. In Part B, participants with hepatitis C virus (HCV) GT1 and HCV ribonucleic acid (RNA) levels of ≥10,000 IU/mL will be randomly assigned to a study arm, based on absence or presence of cirrhosis (C), whether they are TN or had poor response to previous antiviral therapy (null responders \[NR\]), or whether co-infected with human immunodeficiency virus (HIV); these participants will receive open-label grazoprevir (100 mg) in combination with elbasvir (50 mg) ± RBV. Treatment will last 8 to 18 weeks dependent on arm assignment. In Part C, TN, N-C participants with HCV GT1b and HCV RNA levels of ≥10,000 IU/mL will be randomly assigned to receive open-label grazoprevir (100 mg) in combination with elbasvir (50 mg) ± RBV. Treatment will last 8 weeks. In Part D, TN N-C participants with HCV GT3 and HCV RNA levels of ≥10,000 IU/mL will be randomly assigned to receive open-label grazoprevir (100 mg) in combination with elbasvir (50 mg) + RBV for 12 or 18 weeks.
Interventions
DRUGGrazoprevir
100 mg tablet orally QD
DRUGElbasvir
Part A: 20 or 50 mg capsule orally QD Parts B, C, and D: 50 mg capsule orally QD
Placebo to Elbasvir 20 or 50 mg capsule, orally, once daily for 12 weeks to maintain blind (Part A only)
DRUGRibavirin
Oral capsules BID at a total daily dose from 800 to 1400 mg based on participant weight
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
All participants * CHC genotype 1 (GT1) virus infection (Parts A, B, and C) or GT3 virus infection (Part D) * Female participants of childbearing potential or male participant with female partners of childbearing potential, must use two acceptable methods of birth control from ≥2 weeks prior to Day 1 until ≥6 months after last dose of study drug, or longer if dictated by local regulations Part A - Absence (no medical history or physical findings) of ascites, bleeding esophageal varices, hepatic encephalopathy, or other signs or symptoms of advanced liver disease, or cirrhosis - No evidence of advanced fibrosis, cirrhosis and/or hepatocellular carcinoma by biopsy or noninvasive testing (FibroScan and/or FibroTest) Parts B, C, and D * Treatment naïve with or without cirrhosis, or * Prior treatment failure to Peg-IFN/Ribavirin with or without cirrhosis, or * Co-infected with human immunodeficiency virus (HIV) without cirrhosis * Absence (no medical history or physical findings) of ascites, bleeding esophageal varices, hepatic encephalopathy, or other signs or symptoms of advanced liver disease * Liver disease staging assessment by liver biopsy or noninvasive testing (FibroScan and/or FibroTest)
Exclusion criteria
All participants * Non-GT1 HCV infection (Part A, Part B, and Part C) or a non-GT3 HCV infection (Part D) including a mixed GT infection (with a non-GT1 \[Part A, Part B, and Part C\] or non-GT3 \[Part D\]) or a non-typeable genotype * Evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC * Currently participating or 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 study * Diabetic and/or hypertensive with clinically significant ocular examination findings * History of depression associated with hospitalization for depression, electroconvulsive therapy, or resulting in prolonged absence from work and/or significant disruption of daily functions * Suicidal or homicidal ideations and/or attempt, or history of severe psychiatric disorders * Clinical diagnosis of substance abuse * Current history of seizure disorder, stroke, or transient ischemic attack * Immunologically mediated disease * Chronic pulmonary disease * Clinically significant cardiac abnormalities/dysfunction * Active clinical gout within the last year * Hemoglobinopathy or myelodysplastic syndromes * History of organ transplants including hematopoietic stem cell transplants * Poor venous access * Indwelling venous catheter * History of gastric surgery or malabsorption disorders * Severe concurrent disease * Evidence of active or suspected malignancy, or a history of malignancy, ≤5 years before * Pregnant, lactating, expecting to conceive or donate eggs * Male participant with pregnant female partner * Member/family member of the investigational study or sponsor staff directly involved with this study * Evidence or history of chronic hepatitis not caused by HCV Part A * Not treatment-naïve * Documented to be HIV positive * Taking or planning to take significant inducers or inhibitors of CYP3A4 substrates or herbal supplements 2 weeks prior to start of study medications Parts B, C, and D * Previously received any HCV direct-acting antivirals * Requiring, or likely to require, chronic systemic administration of corticosteroids during the course of the trial * For participants diagnosed with diabetes mellitus, documented HbA1c \>8.5%
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12) | 12 weeks after end of therapy (up to 30 weeks) | Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a lower limit of quantification of 25 IU/mL and a limit of detection of 15.1 IU/mL (in plasma). SVR12 was defined as HCV RNA \<25 IU/ml at 12 weeks after the end of all study therapy. 95% confidence intervals provided based on the Clopper-Pearson method. |
| Percentage of Participants Experiencing at Least One Adverse Event (AE) During the Treatment Period and First 14 Follow-up Days | From Day 1 [post-dose] through 14 days following last dose of study drug (up to 20 weeks) | An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product, was also an AE. |
| Percentage of Participants Discontinuing Study Therapy Due to an AE During the Treatment Period and First 14 Follow-up Days | From Day 1 [post-dose] through 14 days following last dose of study drug (up to 20 weeks) | An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product, was also an AE. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Undetectable HCV RNA at Week 12 | Week 12 | HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at various time points prior to, during, and after dosing. Undetectable HCV RNA was defined as below the 15.1 IU/ml limit of detection. The percentage of participants achieving undetectable HCV RNA and accompanying 95% CIs were reported at TW12 for each treatment arm of the PP Population (as applicable). 95% confidence intervals provided based on the Clopper-Pearson method. |
| Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 2 | Week 2 | HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a LLoQ of 25 IU/mL and a limit of detection of 15.1 IU/mL (in plasma). The percentage of participants achieving HCV RNA levels \<25 IU/ml and accompanying 95% CIs were reported at TW2 for each treatment arm of the PP Population. 95% confidence intervals provided based on the Clopper-Pearson method. |
| Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 4 | Week 4 | HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a LLoQ of 25 IU/mL and a limit of detection of 15.1 IU/mL (in plasma). The percentage of participants achieving HCV RNA levels \<25 IU/ml and accompanying 95% CIs were reported at TW4 for each treatment arm of the PP Population. 95% confidence intervals provided based on the Clopper-Pearson method. |
| Mean Time to First Achievement of Undetectable Hepatitis C Virus Ribonucleic Acid (HCV RNA) | From first dose of study medication until first achievement of undetectable HCV RNA (up to 18 weeks of treatment) | Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. Kaplan Meier summary statistics were used to characterize the time to first achievement of undetectable HCV RNA. |
| Percentage of Participants Achieving Sustained Virologic Response 4 Weeks After the End of All Therapy (SVR4) | 4 weeks after end of therapy (up to 22 weeks) | Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a LLoQ of 25 IU/mL and a limit of detection of 15.1 IU/mL (in plasma). SVR4 was defined as HCV RNA \<25 IU/ml at 4 weeks after the end of all study therapy. 95% confidence intervals provided based on the Clopper-Pearson method. |
| Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of All Study Therapy (SVR24) | 24 weeks after end of therapy (up to 42 weeks) | Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a LLoQ of 25 IU/mL and a limit of detection of 15.1 IU/mL (in plasma). SVR24 was defined as HCV RNA \<25 IU/ml at 24 weeks after the end of all study therapy. 95% confidence intervals provided based on the Clopper-Pearson method. |
| Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 12 | Week 12 | HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a LLoQ of 25 IU/mL and a limit of detection of 15.1 IU/mL (in plasma). The percentage of participants achieving HCV RNA levels \<25 IU/ml and accompanying 95% CIs were reported at TW12 for each treatment arm of the PP Population (as applicable). 95% confidence intervals provided based on the Clopper-Pearson method. |
| Percentage of Participants Achieving Undetectable HCV RNA at Week 2 | Week 2 | HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at various time points prior to, during, and after dosing. Undetectable HCV RNA was defined as below the 15.1 IU/ml limit of detection. The percentage of participants achieving undetectable HCV RNA and accompanying 95% CIs were reported at TW2 for each treatment arm of the PP Population. 95% confidence intervals provided based on the Clopper-Pearson method. |
| Percentage of Participants Achieving Undetectable HCV RNA at Week 4 | Week 4 | HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at various time points prior to, during, and after dosing. Undetectable HCV RNA was defined as below the 15.1 IU/ml limit of detection. The percentage of participants achieving undetectable HCV RNA and accompanying 95% CIs were reported at TW4 for each treatment arm of the PP Population. 95% confidence intervals provided based on the Clopper-Pearson method. |
Participant flow
Recruitment details
Male/female participants with Hepatitis C Virus (HCV) genotype 1 (GT1) or GT3 who were either treatment-naïve (TN) or prior null responder (NR), cirrhotic (C) or noncirrhotic (NC), and monoinfected with HCV or coinfected with HCV and human immunodeficiency virus (HIV) were recruited based on entry requirements for Parts A, B, C, or D.
Pre-assignment details
573 participants were randomized on study. 65 TN NC GT1 participants were randomized in Part A. Part B randomized 94 TN NC participants, 123 TN C participants, 130 NR participants (C and NC), and 59 TN HIV coinfected participants. Part C randomized 61 TN NC GT1b participants, and Part D randomized 41 TN NC GT3 participants.
Participants by arm
| Arm | Count |
|---|---|
| A1: TN NC Grazoprevir 100 mg + Elbasvir 20 mg + RBV-12 wk GT1a and GT1b participants receive Grazoprevir 100 mg tablet orally once daily (QD) for 12 weeks, Elbasvir 20 mg capsule and Placebo capsule orally QD for 12 weeks, RBV capsules orally twice daily (BID) for 24 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | 25 |
| A2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk GT1a and GT1b participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule and Placebo capsule orally QD for 12 weeks, RBV capsules orally BID for 24 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | 27 |
| A3: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk GT1b only participants receive Grazoprevr 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | 13 |
| B1: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk GT1a only participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | 30 |
| B2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | 33 |
| B3: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk GT1a only participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | 31 |
| B4: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | 31 |
| B5: TN C Grazoprevir 100 mg + Elbasvir 50 mg for 12 wk GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | 29 |
| B6: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks, RBV capsules orally BID for 18 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | 32 |
| B7: TN C Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks. | 31 |
| B8: NR Grazoprevir 100 mg + Elbasvir 50 mg +RBV-12 wk GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | 32 |
| B9: NR Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | 33 |
| B10: NR Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | 33 |
| B11: NR Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks. | 32 |
| B12: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | 29 |
| B13: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | 30 |
| C1: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk GT1b participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, and RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | 30 |
| C2: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-8 wk GT1b participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks and Elbasvir 50 mg capsule orally QD for 8 weeks. | 31 |
| D1: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk GT3 participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, and RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | 20 |
| D2: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk GT3 participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks, and RBV capsules orally BID for 18 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | 21 |
| Total | 573 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 | FG016 | FG017 | FG018 | FG019 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 3 | 0 | 0 | 2 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 2 | 1 | 0 | 2 | 3 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 2 | 3 |
Baseline characteristics
| Characteristic | A1: TN NC Grazoprevir 100 mg + Elbasvir 20 mg + RBV-12 wk | A2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | A3: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B1: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | B2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B3: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B4: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B5: TN C Grazoprevir 100 mg + Elbasvir 50 mg for 12 wk | B6: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | B7: TN C Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | B8: NR Grazoprevir 100 mg + Elbasvir 50 mg +RBV-12 wk | B9: NR Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B10: NR Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | B11: NR Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | B12: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B13: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | C1: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | C2: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-8 wk | D1: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | D2: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 48.7 years STANDARD_DEVIATION 12.5 | 43.9 years STANDARD_DEVIATION 12.6 | 43.3 years STANDARD_DEVIATION 13.5 | 48.4 years STANDARD_DEVIATION 11.9 | 49.7 years STANDARD_DEVIATION 11.5 | 53.6 years STANDARD_DEVIATION 8.4 | 57.0 years STANDARD_DEVIATION 7 | 59.0 years STANDARD_DEVIATION 7.8 | 58.8 years STANDARD_DEVIATION 8.2 | 58.9 years STANDARD_DEVIATION 8 | 52.2 years STANDARD_DEVIATION 8.8 | 54.4 years STANDARD_DEVIATION 9.1 | 56.2 years STANDARD_DEVIATION 10.9 | 54.3 years STANDARD_DEVIATION 12.3 | 46.2 years STANDARD_DEVIATION 8.4 | 43.5 years STANDARD_DEVIATION 10.4 | 50.6 years STANDARD_DEVIATION 10.9 | 55.3 years STANDARD_DEVIATION 10.3 | 49.0 years STANDARD_DEVIATION 11.5 | 42.4 years STANDARD_DEVIATION 10.8 | 51.9 years STANDARD_DEVIATION 11.3 |
| Sex: Female, Male Female | 13 Participants | 17 Participants | 6 Participants | 12 Participants | 15 Participants | 15 Participants | 12 Participants | 10 Participants | 17 Participants | 10 Participants | 12 Participants | 13 Participants | 17 Participants | 14 Participants | 6 Participants | 6 Participants | 14 Participants | 18 Participants | 12 Participants | 13 Participants | 252 Participants |
| Sex: Female, Male Male | 12 Participants | 10 Participants | 7 Participants | 18 Participants | 18 Participants | 16 Participants | 19 Participants | 19 Participants | 15 Participants | 21 Participants | 20 Participants | 20 Participants | 16 Participants | 18 Participants | 23 Participants | 24 Participants | 16 Participants | 13 Participants | 8 Participants | 8 Participants | 321 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 19 / 25 | 24 / 28 | 11 / 12 | 27 / 30 | 23 / 33 | 24 / 31 | 23 / 31 | 18 / 29 | 26 / 32 | 24 / 31 | 24 / 32 | 25 / 33 | 32 / 33 | 25 / 32 | 18 / 29 | 14 / 30 | 22 / 30 | 14 / 31 | 16 / 20 | 20 / 21 |
| serious Total, serious adverse events | 1 / 25 | 0 / 28 | 0 / 12 | 0 / 30 | 0 / 33 | 0 / 31 | 1 / 31 | 2 / 29 | 1 / 32 | 1 / 31 | 2 / 32 | 1 / 33 | 0 / 33 | 1 / 32 | 1 / 29 | 2 / 30 | 1 / 30 | 0 / 31 | 0 / 20 | 2 / 21 |
Outcome results
Primary
Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12)
Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a lower limit of quantification of 25 IU/mL and a limit of detection of 15.1 IU/mL (in plasma). SVR12 was defined as HCV RNA \<25 IU/ml at 12 weeks after the end of all study therapy. 95% confidence intervals provided based on the Clopper-Pearson method.
Time frame: 12 weeks after end of therapy (up to 30 weeks)
Population: The Per-Protocol (PP) population; all randomized participants who received ≥1 dose of study treatment and without important protocol deviations who had data available at the respective time point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A1: TN NC Grazoprevir 100 mg + Elbasvir 20 mg + RBV-12 wk | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12) | 100.0 percentage of participants |
| A2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12) | 95.8 percentage of participants |
| A3: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12) | 100.0 percentage of participants |
| B1: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12) | 82.8 percentage of participants |
| B2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12) | 100.0 percentage of participants |
| B3: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12) | 96.8 percentage of participants |
| B4: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12) | 90.0 percentage of participants |
| B5: TN C Grazoprevir 100 mg + Elbasvir 50 mg for 12 wk | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12) | 96.6 percentage of participants |
| B6: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12) | 100.0 percentage of participants |
| B7: TN C Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12) | 93.5 percentage of participants |
| B8: NR Grazoprevir 100 mg + Elbasvir 50 mg +RBV-12 wk | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12) | 100.0 percentage of participants |
| B9: NR Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12) | 90.9 percentage of participants |
| B10: NR Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12) | 100.0 percentage of participants |
| B11: NR Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12) | 96.9 percentage of participants |
| B12: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12) | 96.6 percentage of participants |
| B13: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12) | 92.9 percentage of participants |
| C1: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12) | 93.1 percentage of participants |
| C2: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-8 wk | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12) | 93.5 percentage of participants |
| D1: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12) | 47.4 percentage of participants |
| D2: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12) | 61.1 percentage of participants |
Primary
Percentage of Participants Discontinuing Study Therapy Due to an AE During the Treatment Period and First 14 Follow-up Days
An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product, was also an AE.
Time frame: From Day 1 [post-dose] through 14 days following last dose of study drug (up to 20 weeks)
Population: APaT population; all randomized who received ≥1 dose of study treatment according to treatment actually received. One participant randomized to A3 arm was treated on A2 arm and thus was counted under the A2 arm (n=28).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A1: TN NC Grazoprevir 100 mg + Elbasvir 20 mg + RBV-12 wk | Percentage of Participants Discontinuing Study Therapy Due to an AE During the Treatment Period and First 14 Follow-up Days | 0.0 percentage of participants |
| A2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Discontinuing Study Therapy Due to an AE During the Treatment Period and First 14 Follow-up Days | 0.0 percentage of participants |
| A3: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Percentage of Participants Discontinuing Study Therapy Due to an AE During the Treatment Period and First 14 Follow-up Days | 0.0 percentage of participants |
| B1: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | Percentage of Participants Discontinuing Study Therapy Due to an AE During the Treatment Period and First 14 Follow-up Days | 0.0 percentage of participants |
| B2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Discontinuing Study Therapy Due to an AE During the Treatment Period and First 14 Follow-up Days | 0.0 percentage of participants |
| B3: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Percentage of Participants Discontinuing Study Therapy Due to an AE During the Treatment Period and First 14 Follow-up Days | 0.0 percentage of participants |
| B4: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Discontinuing Study Therapy Due to an AE During the Treatment Period and First 14 Follow-up Days | 0.0 percentage of participants |
| B5: TN C Grazoprevir 100 mg + Elbasvir 50 mg for 12 wk | Percentage of Participants Discontinuing Study Therapy Due to an AE During the Treatment Period and First 14 Follow-up Days | 0.0 percentage of participants |
| B6: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | Percentage of Participants Discontinuing Study Therapy Due to an AE During the Treatment Period and First 14 Follow-up Days | 6.3 percentage of participants |
| B7: TN C Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | Percentage of Participants Discontinuing Study Therapy Due to an AE During the Treatment Period and First 14 Follow-up Days | 0.0 percentage of participants |
| B8: NR Grazoprevir 100 mg + Elbasvir 50 mg +RBV-12 wk | Percentage of Participants Discontinuing Study Therapy Due to an AE During the Treatment Period and First 14 Follow-up Days | 3.1 percentage of participants |
| B9: NR Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Percentage of Participants Discontinuing Study Therapy Due to an AE During the Treatment Period and First 14 Follow-up Days | 0.0 percentage of participants |
| B10: NR Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | Percentage of Participants Discontinuing Study Therapy Due to an AE During the Treatment Period and First 14 Follow-up Days | 0.0 percentage of participants |
| B11: NR Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | Percentage of Participants Discontinuing Study Therapy Due to an AE During the Treatment Period and First 14 Follow-up Days | 0.0 percentage of participants |
| B12: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Discontinuing Study Therapy Due to an AE During the Treatment Period and First 14 Follow-up Days | 0.0 percentage of participants |
| B13: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Percentage of Participants Discontinuing Study Therapy Due to an AE During the Treatment Period and First 14 Follow-up Days | 0.0 percentage of participants |
| C1: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | Percentage of Participants Discontinuing Study Therapy Due to an AE During the Treatment Period and First 14 Follow-up Days | 0.0 percentage of participants |
| C2: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-8 wk | Percentage of Participants Discontinuing Study Therapy Due to an AE During the Treatment Period and First 14 Follow-up Days | 0.0 percentage of participants |
| D1: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Discontinuing Study Therapy Due to an AE During the Treatment Period and First 14 Follow-up Days | 0.0 percentage of participants |
| D2: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | Percentage of Participants Discontinuing Study Therapy Due to an AE During the Treatment Period and First 14 Follow-up Days | 4.8 percentage of participants |
Primary
Percentage of Participants Experiencing at Least One Adverse Event (AE) During the Treatment Period and First 14 Follow-up Days
An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product, was also an AE.
Time frame: From Day 1 [post-dose] through 14 days following last dose of study drug (up to 20 weeks)
Population: All Participants as Treated (APaT) population; all randomized who received ≥1 dose of study treatment according to treatment actually received. One participant randomized to A3 arm was treated on A2 arm and thus was counted under the A2 arm (n=28).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A1: TN NC Grazoprevir 100 mg + Elbasvir 20 mg + RBV-12 wk | Percentage of Participants Experiencing at Least One Adverse Event (AE) During the Treatment Period and First 14 Follow-up Days | 88.0 percentage of participants |
| A2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Experiencing at Least One Adverse Event (AE) During the Treatment Period and First 14 Follow-up Days | 85.7 percentage of participants |
| A3: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Percentage of Participants Experiencing at Least One Adverse Event (AE) During the Treatment Period and First 14 Follow-up Days | 91.7 percentage of participants |
| B1: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | Percentage of Participants Experiencing at Least One Adverse Event (AE) During the Treatment Period and First 14 Follow-up Days | 90.0 percentage of participants |
| B2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Experiencing at Least One Adverse Event (AE) During the Treatment Period and First 14 Follow-up Days | 72.7 percentage of participants |
| B3: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Percentage of Participants Experiencing at Least One Adverse Event (AE) During the Treatment Period and First 14 Follow-up Days | 87.1 percentage of participants |
| B4: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Experiencing at Least One Adverse Event (AE) During the Treatment Period and First 14 Follow-up Days | 77.4 percentage of participants |
| B5: TN C Grazoprevir 100 mg + Elbasvir 50 mg for 12 wk | Percentage of Participants Experiencing at Least One Adverse Event (AE) During the Treatment Period and First 14 Follow-up Days | 65.5 percentage of participants |
| B6: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | Percentage of Participants Experiencing at Least One Adverse Event (AE) During the Treatment Period and First 14 Follow-up Days | 87.5 percentage of participants |
| B7: TN C Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | Percentage of Participants Experiencing at Least One Adverse Event (AE) During the Treatment Period and First 14 Follow-up Days | 83.9 percentage of participants |
| B8: NR Grazoprevir 100 mg + Elbasvir 50 mg +RBV-12 wk | Percentage of Participants Experiencing at Least One Adverse Event (AE) During the Treatment Period and First 14 Follow-up Days | 81.3 percentage of participants |
| B9: NR Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Percentage of Participants Experiencing at Least One Adverse Event (AE) During the Treatment Period and First 14 Follow-up Days | 78.8 percentage of participants |
| B10: NR Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | Percentage of Participants Experiencing at Least One Adverse Event (AE) During the Treatment Period and First 14 Follow-up Days | 97.0 percentage of participants |
| B11: NR Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | Percentage of Participants Experiencing at Least One Adverse Event (AE) During the Treatment Period and First 14 Follow-up Days | 81.3 percentage of participants |
| B12: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Experiencing at Least One Adverse Event (AE) During the Treatment Period and First 14 Follow-up Days | 65.5 percentage of participants |
| B13: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Percentage of Participants Experiencing at Least One Adverse Event (AE) During the Treatment Period and First 14 Follow-up Days | 53.3 percentage of participants |
| C1: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | Percentage of Participants Experiencing at Least One Adverse Event (AE) During the Treatment Period and First 14 Follow-up Days | 73.3 percentage of participants |
| C2: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-8 wk | Percentage of Participants Experiencing at Least One Adverse Event (AE) During the Treatment Period and First 14 Follow-up Days | 54.8 percentage of participants |
| D1: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Experiencing at Least One Adverse Event (AE) During the Treatment Period and First 14 Follow-up Days | 85.0 percentage of participants |
| D2: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | Percentage of Participants Experiencing at Least One Adverse Event (AE) During the Treatment Period and First 14 Follow-up Days | 90.5 percentage of participants |
Secondary
Mean Time to First Achievement of Undetectable Hepatitis C Virus Ribonucleic Acid (HCV RNA)
Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. Kaplan Meier summary statistics were used to characterize the time to first achievement of undetectable HCV RNA.
Time frame: From first dose of study medication until first achievement of undetectable HCV RNA (up to 18 weeks of treatment)
Population: FAS; all randomized participants who received ≥1 dose of study treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| A1: TN NC Grazoprevir 100 mg + Elbasvir 20 mg + RBV-12 wk | Mean Time to First Achievement of Undetectable Hepatitis C Virus Ribonucleic Acid (HCV RNA) | 21.7 days | Standard Error 2.2 |
| A2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Mean Time to First Achievement of Undetectable Hepatitis C Virus Ribonucleic Acid (HCV RNA) | 19.2 days | Standard Error 1.8 |
| A3: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Mean Time to First Achievement of Undetectable Hepatitis C Virus Ribonucleic Acid (HCV RNA) | 23.4 days | Standard Error 2.9 |
| B1: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | Mean Time to First Achievement of Undetectable Hepatitis C Virus Ribonucleic Acid (HCV RNA) | 27.9 days | Standard Error 3 |
| B2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Mean Time to First Achievement of Undetectable Hepatitis C Virus Ribonucleic Acid (HCV RNA) | 30.7 days | Standard Error 2.3 |
| B3: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Mean Time to First Achievement of Undetectable Hepatitis C Virus Ribonucleic Acid (HCV RNA) | 32.0 days | Standard Error 3 |
| B4: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Mean Time to First Achievement of Undetectable Hepatitis C Virus Ribonucleic Acid (HCV RNA) | 37.0 days | Standard Error 2.8 |
| B5: TN C Grazoprevir 100 mg + Elbasvir 50 mg for 12 wk | Mean Time to First Achievement of Undetectable Hepatitis C Virus Ribonucleic Acid (HCV RNA) | 33.2 days | Standard Error 2.4 |
| B6: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | Mean Time to First Achievement of Undetectable Hepatitis C Virus Ribonucleic Acid (HCV RNA) | 33.1 days | Standard Error 2.8 |
| B7: TN C Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | Mean Time to First Achievement of Undetectable Hepatitis C Virus Ribonucleic Acid (HCV RNA) | 33.7 days | Standard Error 2.6 |
| B8: NR Grazoprevir 100 mg + Elbasvir 50 mg +RBV-12 wk | Mean Time to First Achievement of Undetectable Hepatitis C Virus Ribonucleic Acid (HCV RNA) | 31.9 days | Standard Error 2.2 |
| B9: NR Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Mean Time to First Achievement of Undetectable Hepatitis C Virus Ribonucleic Acid (HCV RNA) | 37.4 days | Standard Error 2.5 |
| B10: NR Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | Mean Time to First Achievement of Undetectable Hepatitis C Virus Ribonucleic Acid (HCV RNA) | 37.4 days | Standard Error 2.7 |
| B11: NR Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | Mean Time to First Achievement of Undetectable Hepatitis C Virus Ribonucleic Acid (HCV RNA) | 42.7 days | Standard Error 3.3 |
| B12: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Mean Time to First Achievement of Undetectable Hepatitis C Virus Ribonucleic Acid (HCV RNA) | 27.6 days | Standard Error 3 |
| B13: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Mean Time to First Achievement of Undetectable Hepatitis C Virus Ribonucleic Acid (HCV RNA) | 29.0 days | Standard Error 2.9 |
| C1: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | Mean Time to First Achievement of Undetectable Hepatitis C Virus Ribonucleic Acid (HCV RNA) | 23.7 days | Standard Error 2.1 |
| C2: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-8 wk | Mean Time to First Achievement of Undetectable Hepatitis C Virus Ribonucleic Acid (HCV RNA) | 34.5 days | Standard Error 2.6 |
| D1: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Mean Time to First Achievement of Undetectable Hepatitis C Virus Ribonucleic Acid (HCV RNA) | 30.1 days | Standard Error 3.7 |
| D2: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | Mean Time to First Achievement of Undetectable Hepatitis C Virus Ribonucleic Acid (HCV RNA) | 19.8 days | Standard Error 2.3 |
Secondary
Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 12
HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a LLoQ of 25 IU/mL and a limit of detection of 15.1 IU/mL (in plasma). The percentage of participants achieving HCV RNA levels \<25 IU/ml and accompanying 95% CIs were reported at TW12 for each treatment arm of the PP Population (as applicable). 95% confidence intervals provided based on the Clopper-Pearson method.
Time frame: Week 12
Population: The PP population; all randomized participants who received ≥1 dose of study treatment and without important protocol deviations who had data available at the respective time point. The B1, C1, and C2 arms only received 8 weeks of treatment and were thus excluded from this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A1: TN NC Grazoprevir 100 mg + Elbasvir 20 mg + RBV-12 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 12 | 100.0 percentage of participants |
| A2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 12 | 100.0 percentage of participants |
| A3: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 12 | 100.0 percentage of participants |
| B2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 12 | 100.0 percentage of participants |
| B3: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 12 | 100.0 percentage of participants |
| B4: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 12 | 93.3 percentage of participants |
| B5: TN C Grazoprevir 100 mg + Elbasvir 50 mg for 12 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 12 | 100.0 percentage of participants |
| B6: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 12 | 100.0 percentage of participants |
| B7: TN C Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 12 | 100.0 percentage of participants |
| B8: NR Grazoprevir 100 mg + Elbasvir 50 mg +RBV-12 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 12 | 100.0 percentage of participants |
| B9: NR Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 12 | 100.0 percentage of participants |
| B10: NR Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 12 | 100.0 percentage of participants |
| B11: NR Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 12 | 96.9 percentage of participants |
| B12: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 12 | 100.0 percentage of participants |
| B13: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 12 | 92.9 percentage of participants |
| D1: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 12 | 47.4 percentage of participants |
| D2: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 12 | 75.0 percentage of participants |
Secondary
Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 2
HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a LLoQ of 25 IU/mL and a limit of detection of 15.1 IU/mL (in plasma). The percentage of participants achieving HCV RNA levels \<25 IU/ml and accompanying 95% CIs were reported at TW2 for each treatment arm of the PP Population. 95% confidence intervals provided based on the Clopper-Pearson method.
Time frame: Week 2
Population: The PP population; all randomized participants who received ≥1 dose of study treatment and without important protocol deviations who had data available at the respective time point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A1: TN NC Grazoprevir 100 mg + Elbasvir 20 mg + RBV-12 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 2 | 91.3 percentage of participants |
| A2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 2 | 92.0 percentage of participants |
| A3: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 2 | 91.7 percentage of participants |
| B1: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 2 | 86.2 percentage of participants |
| B2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 2 | 73.3 percentage of participants |
| B3: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 2 | 77.4 percentage of participants |
| B4: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 2 | 60.0 percentage of participants |
| B5: TN C Grazoprevir 100 mg + Elbasvir 50 mg for 12 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 2 | 79.3 percentage of participants |
| B6: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 2 | 78.1 percentage of participants |
| B7: TN C Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 2 | 67.7 percentage of participants |
| B8: NR Grazoprevir 100 mg + Elbasvir 50 mg +RBV-12 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 2 | 77.4 percentage of participants |
| B9: NR Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 2 | 66.7 percentage of participants |
| B10: NR Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 2 | 57.6 percentage of participants |
| B11: NR Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 2 | 62.5 percentage of participants |
| B12: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 2 | 89.7 percentage of participants |
| B13: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 2 | 76.7 percentage of participants |
| C1: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 2 | 76.7 percentage of participants |
| C2: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-8 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 2 | 61.3 percentage of participants |
| D1: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 2 | 70.0 percentage of participants |
| D2: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 2 | 85.0 percentage of participants |
Secondary
Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 4
HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a LLoQ of 25 IU/mL and a limit of detection of 15.1 IU/mL (in plasma). The percentage of participants achieving HCV RNA levels \<25 IU/ml and accompanying 95% CIs were reported at TW4 for each treatment arm of the PP Population. 95% confidence intervals provided based on the Clopper-Pearson method.
Time frame: Week 4
Population: The PP population; all randomized participants who received ≥1 dose of study treatment and without important protocol deviations who had data available at the respective time point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A1: TN NC Grazoprevir 100 mg + Elbasvir 20 mg + RBV-12 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 4 | 100.0 percentage of participants |
| A2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 4 | 100.0 percentage of participants |
| A3: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 4 | 100.0 percentage of participants |
| B1: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 4 | 100.0 percentage of participants |
| B2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 4 | 100.0 percentage of participants |
| B3: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 4 | 100.0 percentage of participants |
| B4: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 4 | 90.0 percentage of participants |
| B5: TN C Grazoprevir 100 mg + Elbasvir 50 mg for 12 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 4 | 100.0 percentage of participants |
| B6: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 4 | 100.0 percentage of participants |
| B7: TN C Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 4 | 90.3 percentage of participants |
| B8: NR Grazoprevir 100 mg + Elbasvir 50 mg +RBV-12 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 4 | 100.0 percentage of participants |
| B9: NR Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 4 | 96.9 percentage of participants |
| B10: NR Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 4 | 97.0 percentage of participants |
| B11: NR Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 4 | 93.8 percentage of participants |
| B12: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 4 | 100.0 percentage of participants |
| B13: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 4 | 100.0 percentage of participants |
| C1: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 4 | 100.0 percentage of participants |
| C2: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-8 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 4 | 96.8 percentage of participants |
| D1: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 4 | 65.0 percentage of participants |
| D2: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 4 | 83.3 percentage of participants |
Secondary
Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of All Study Therapy (SVR24)
Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a LLoQ of 25 IU/mL and a limit of detection of 15.1 IU/mL (in plasma). SVR24 was defined as HCV RNA \<25 IU/ml at 24 weeks after the end of all study therapy. 95% confidence intervals provided based on the Clopper-Pearson method.
Time frame: 24 weeks after end of therapy (up to 42 weeks)
Population: The PP population; all randomized participants who received ≥1 dose of study treatment and without important protocol deviations who had data available at the respective time point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A1: TN NC Grazoprevir 100 mg + Elbasvir 20 mg + RBV-12 wk | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of All Study Therapy (SVR24) | 100.0 percentage of participants |
| A2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of All Study Therapy (SVR24) | 95.8 percentage of participants |
| A3: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of All Study Therapy (SVR24) | 100.0 percentage of participants |
| B1: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of All Study Therapy (SVR24) | 78.6 percentage of participants |
| B2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of All Study Therapy (SVR24) | 100.0 percentage of participants |
| B3: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of All Study Therapy (SVR24) | 96.8 percentage of participants |
| B4: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of All Study Therapy (SVR24) | 90.0 percentage of participants |
| B5: TN C Grazoprevir 100 mg + Elbasvir 50 mg for 12 wk | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of All Study Therapy (SVR24) | 96.6 percentage of participants |
| B6: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of All Study Therapy (SVR24) | 100.0 percentage of participants |
| B7: TN C Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of All Study Therapy (SVR24) | 93.1 percentage of participants |
| B8: NR Grazoprevir 100 mg + Elbasvir 50 mg +RBV-12 wk | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of All Study Therapy (SVR24) | 100.0 percentage of participants |
| B9: NR Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of All Study Therapy (SVR24) | 90.9 percentage of participants |
| B10: NR Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of All Study Therapy (SVR24) | 100.0 percentage of participants |
| B11: NR Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of All Study Therapy (SVR24) | 96.9 percentage of participants |
| B12: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of All Study Therapy (SVR24) | 96.6 percentage of participants |
| B13: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of All Study Therapy (SVR24) | 88.9 percentage of participants |
| C1: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of All Study Therapy (SVR24) | 93.1 percentage of participants |
| C2: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-8 wk | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of All Study Therapy (SVR24) | 93.5 percentage of participants |
| D1: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of All Study Therapy (SVR24) | 47.4 percentage of participants |
| D2: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of All Study Therapy (SVR24) | 58.8 percentage of participants |
Secondary
Percentage of Participants Achieving Sustained Virologic Response 4 Weeks After the End of All Therapy (SVR4)
Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a LLoQ of 25 IU/mL and a limit of detection of 15.1 IU/mL (in plasma). SVR4 was defined as HCV RNA \<25 IU/ml at 4 weeks after the end of all study therapy. 95% confidence intervals provided based on the Clopper-Pearson method.
Time frame: 4 weeks after end of therapy (up to 22 weeks)
Population: The PP population; all randomized participants who received ≥1 dose of study treatment and without important protocol deviations who had data available at the respective time point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A1: TN NC Grazoprevir 100 mg + Elbasvir 20 mg + RBV-12 wk | Percentage of Participants Achieving Sustained Virologic Response 4 Weeks After the End of All Therapy (SVR4) | 100.0 percentage of participants |
| A2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving Sustained Virologic Response 4 Weeks After the End of All Therapy (SVR4) | 95.8 percentage of participants |
| A3: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Percentage of Participants Achieving Sustained Virologic Response 4 Weeks After the End of All Therapy (SVR4) | 100.0 percentage of participants |
| B1: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | Percentage of Participants Achieving Sustained Virologic Response 4 Weeks After the End of All Therapy (SVR4) | 93.3 percentage of participants |
| B2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving Sustained Virologic Response 4 Weeks After the End of All Therapy (SVR4) | 100.0 percentage of participants |
| B3: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Percentage of Participants Achieving Sustained Virologic Response 4 Weeks After the End of All Therapy (SVR4) | 96.8 percentage of participants |
| B4: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving Sustained Virologic Response 4 Weeks After the End of All Therapy (SVR4) | 96.7 percentage of participants |
| B5: TN C Grazoprevir 100 mg + Elbasvir 50 mg for 12 wk | Percentage of Participants Achieving Sustained Virologic Response 4 Weeks After the End of All Therapy (SVR4) | 96.6 percentage of participants |
| B6: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | Percentage of Participants Achieving Sustained Virologic Response 4 Weeks After the End of All Therapy (SVR4) | 100.0 percentage of participants |
| B7: TN C Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | Percentage of Participants Achieving Sustained Virologic Response 4 Weeks After the End of All Therapy (SVR4) | 96.8 percentage of participants |
| B8: NR Grazoprevir 100 mg + Elbasvir 50 mg +RBV-12 wk | Percentage of Participants Achieving Sustained Virologic Response 4 Weeks After the End of All Therapy (SVR4) | 100.0 percentage of participants |
| B9: NR Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Percentage of Participants Achieving Sustained Virologic Response 4 Weeks After the End of All Therapy (SVR4) | 93.9 percentage of participants |
| B10: NR Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | Percentage of Participants Achieving Sustained Virologic Response 4 Weeks After the End of All Therapy (SVR4) | 100.0 percentage of participants |
| B11: NR Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | Percentage of Participants Achieving Sustained Virologic Response 4 Weeks After the End of All Therapy (SVR4) | 96.9 percentage of participants |
| B12: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving Sustained Virologic Response 4 Weeks After the End of All Therapy (SVR4) | 96.6 percentage of participants |
| B13: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Percentage of Participants Achieving Sustained Virologic Response 4 Weeks After the End of All Therapy (SVR4) | 93.1 percentage of participants |
| C1: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | Percentage of Participants Achieving Sustained Virologic Response 4 Weeks After the End of All Therapy (SVR4) | 93.1 percentage of participants |
| C2: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-8 wk | Percentage of Participants Achieving Sustained Virologic Response 4 Weeks After the End of All Therapy (SVR4) | 96.8 percentage of participants |
| D1: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving Sustained Virologic Response 4 Weeks After the End of All Therapy (SVR4) | 50.0 percentage of participants |
| D2: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | Percentage of Participants Achieving Sustained Virologic Response 4 Weeks After the End of All Therapy (SVR4) | 61.1 percentage of participants |
Secondary
Percentage of Participants Achieving Undetectable HCV RNA at Week 12
HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at various time points prior to, during, and after dosing. Undetectable HCV RNA was defined as below the 15.1 IU/ml limit of detection. The percentage of participants achieving undetectable HCV RNA and accompanying 95% CIs were reported at TW12 for each treatment arm of the PP Population (as applicable). 95% confidence intervals provided based on the Clopper-Pearson method.
Time frame: Week 12
Population: The PP population; all randomized participants who received ≥1 dose of study treatment and without important protocol deviations who had data available at the respective time point. The B1, C1, and C2 arms only received 8 weeks of treatment and were thus excluded from this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A1: TN NC Grazoprevir 100 mg + Elbasvir 20 mg + RBV-12 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 12 | 100.0 percentage of participants |
| A2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 12 | 100.0 percentage of participants |
| A3: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 12 | 100.0 percentage of participants |
| B2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 12 | 100.0 percentage of participants |
| B3: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 12 | 100.0 percentage of participants |
| B4: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 12 | 93.3 percentage of participants |
| B5: TN C Grazoprevir 100 mg + Elbasvir 50 mg for 12 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 12 | 96.6 percentage of participants |
| B6: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 12 | 100.0 percentage of participants |
| B7: TN C Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 12 | 100.0 percentage of participants |
| B8: NR Grazoprevir 100 mg + Elbasvir 50 mg +RBV-12 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 12 | 100.0 percentage of participants |
| B9: NR Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 12 | 93.8 percentage of participants |
| B10: NR Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 12 | 100.0 percentage of participants |
| B11: NR Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 12 | 96.9 percentage of participants |
| B12: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 12 | 93.1 percentage of participants |
| B13: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 12 | 92.9 percentage of participants |
| D1: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 12 | 47.7 percentage of participants |
| D2: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 12 | 65.0 percentage of participants |
Secondary
Percentage of Participants Achieving Undetectable HCV RNA at Week 2
HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at various time points prior to, during, and after dosing. Undetectable HCV RNA was defined as below the 15.1 IU/ml limit of detection. The percentage of participants achieving undetectable HCV RNA and accompanying 95% CIs were reported at TW2 for each treatment arm of the PP Population. 95% confidence intervals provided based on the Clopper-Pearson method.
Time frame: Week 2
Population: The PP population; all randomized participants who received ≥1 dose of study treatment and without important protocol deviations who had data available at the respective time point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A1: TN NC Grazoprevir 100 mg + Elbasvir 20 mg + RBV-12 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 2 | 52.2 percentage of participants |
| A2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 2 | 44.0 percentage of participants |
| A3: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 2 | 41.7 percentage of participants |
| B1: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 2 | 44.8 percentage of participants |
| B2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 2 | 20.0 percentage of participants |
| B3: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 2 | 16.1 percentage of participants |
| B4: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 2 | 6.7 percentage of participants |
| B5: TN C Grazoprevir 100 mg + Elbasvir 50 mg for 12 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 2 | 10.3 percentage of participants |
| B6: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 2 | 25.0 percentage of participants |
| B7: TN C Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 2 | 16.1 percentage of participants |
| B8: NR Grazoprevir 100 mg + Elbasvir 50 mg +RBV-12 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 2 | 12.9 percentage of participants |
| B9: NR Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 2 | 6.1 percentage of participants |
| B10: NR Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 2 | 6.1 percentage of participants |
| B11: NR Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 2 | 6.3 percentage of participants |
| B12: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 2 | 37.9 percentage of participants |
| B13: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 2 | 40.0 percentage of participants |
| C1: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 2 | 46.7 percentage of participants |
| C2: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-8 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 2 | 12.9 percentage of participants |
| D1: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 2 | 40.0 percentage of participants |
| D2: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 2 | 70.0 percentage of participants |
Secondary
Percentage of Participants Achieving Undetectable HCV RNA at Week 4
HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at various time points prior to, during, and after dosing. Undetectable HCV RNA was defined as below the 15.1 IU/ml limit of detection. The percentage of participants achieving undetectable HCV RNA and accompanying 95% CIs were reported at TW4 for each treatment arm of the PP Population. 95% confidence intervals provided based on the Clopper-Pearson method.
Time frame: Week 4
Population: The PP population; all randomized participants who received ≥1 dose of study treatment and without important protocol deviations who had data available at the respective time point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A1: TN NC Grazoprevir 100 mg + Elbasvir 20 mg + RBV-12 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 4 | 73.9 percentage of participants |
| A2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 4 | 91.7 percentage of participants |
| A3: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 4 | 75.0 percentage of participants |
| B1: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 4 | 73.3 percentage of participants |
| B2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 4 | 83.3 percentage of participants |
| B3: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 4 | 77.4 percentage of participants |
| B4: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 4 | 60.0 percentage of participants |
| B5: TN C Grazoprevir 100 mg + Elbasvir 50 mg for 12 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 4 | 79.3 percentage of participants |
| B6: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 4 | 71.9 percentage of participants |
| B7: TN C Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 4 | 71.0 percentage of participants |
| B8: NR Grazoprevir 100 mg + Elbasvir 50 mg +RBV-12 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 4 | 83.3 percentage of participants |
| B9: NR Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 4 | 68.8 percentage of participants |
| B10: NR Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 4 | 69.7 percentage of participants |
| B11: NR Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 4 | 53.1 percentage of participants |
| B12: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 4 | 75.9 percentage of participants |
| B13: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 4 | 78.6 percentage of participants |
| C1: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 4 | 86.7 percentage of participants |
| C2: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-8 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 4 | 74.2 percentage of participants |
| D1: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 4 | 50.0 percentage of participants |
| D2: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | Percentage of Participants Achieving Undetectable HCV RNA at Week 4 | 77.8 percentage of participants |