Hepatitis C, Chronic
Conditions
Brief summary
This study will evaluate the safety, tolerability, and antiviral activity of grazoprevir (MK-5172) when administered in combination with peginterferon alfa-2b (Peg-IFN) and ribavirin (RBV) in treatment-naïve (TN) participants with chronic hepatitis C.
Detailed description
Amendment 4 unblinded treatment after an interim analysis for all subsequently enrolled TN participants (the Second Cohort) who were receiving grazoprevir 400 or 800 mg daily, and they were down-dosed to 100 mg daily between Treatment Week (TW) 3 and TW12 for the remainder of the 12-week treatment course. Amendment 5 allowed treatment-naïve participants with chronic hepatitis C and compensated cirrhosis to be enrolled and receive open-label grazoprevir 100 mg in combination with Peg-IFN and RBV, without a corresponding control arm.
Interventions
DRUGPlacebo for Grazoprevir
Orally once daily in AM.
DRUGPlacebo for Boceprevir
Four capsules orally three times daily.
1.5 μg/kg/week subcutaneous injection.
DRUGRibavirin
300 mg to 700 mg orally twice daily.
DRUGGrazoprevir
Orally once daily in AM. Blinded or open-label depending on treatment arm.
DRUGBoceprevir
Four 200 mg capsules orally three times daily.
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
* Has previously documented chronic hepatitis C genotype 1 (CHC GT 1) infection * Has hepatitis C virus (HCV) ribonucleic acid (RNA value) ≥10,000 IU/mL * Body weight ≥40 kg (88 lbs) and ≤125 kg (275 lbs) * Absence (no medical history or physical findings) of ascites, bleeding esophageal varices, hepatic encephalopathy, or other signs and symptoms of decompensated liver disease * Had a liver biopsy within 3 years of screening or between screening and Day 1 with histology consistent with CHC and no evidence of cirrhosis or hepatocellular carcinoma or no other cause for chronic liver disease (for participants with compensated cirrhosis, any liver biopsy demonstrating cirrhosis regardless of length of time since biopsy) * Female of childbearing potential or a male with female sexual partner who is of childbearing potential agrees to use two acceptable methods of birth control from at least 2 weeks prior to Day 1 and continue until at least 6 months after last dose of study drug, or longer if dictated by local regulations * For participants with compensated cirrhosis, evidence of cirrhosis without evidence of hepatocellular carcinoma (confirmed by ultrasound within 4 weeks prior)
Exclusion criteria
* Is pregnant, breastfeeding, or plans to become pregnant or donate eggs * Is human immunodeficiency virus (HIV) positive or known to be co-infected with hepatitis B virus * Has received prior approved or investigational treatment for hepatitis C * Has evidence of hepatocellular carcinoma or is under evaluation for hepatocellular carcinoma * For participants with compensated cirrhosis: alphafetoprotein level of ≥100 ng/mL * Has evidence of active or suspected malignancy, or a history of malignancy, within the last 5 years * Has evidence or history of chronic hepatitis not caused by HCV * Is diabetic and/or hypertensive with clinically significant ocular examination findings: retinopathy, cotton wool spots, optic nerve disorder, retinal hemorrhage, or any other clinically significant abnormality * Has any known medical condition that could interfere with participation in and completion of the study * Pre-existing psychiatric condition including but not limited to moderate or severe depression, suicidal or homicidal ideation or attempt, schizophrenia, psychosis, bipolar disorder, post traumatic stress disorder, or mania * Is currently participating or has participated in a study with an investigational compound or device within 30 days of signing informed consent * Member or family member of study staff
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Complete Early Viral Response (cEVR) | After 12 weeks of treatment with grazoprevir/boceprevir | 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 9.3 IU/mL (in plasma). cEVR was defined as undetectable HCV RNA (target not detected \[TND\]) at Week 12. 95% confidence intervals provided based on the Clopper-Pearson method. |
| Number of Participants Experiencing Adverse Events (AEs) During the Treatment Period and First 14 Follow-up Days | Treatment period plus the first 14 days of follow-up (up to 50 weeks) | An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. 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. |
| Number of Participants Who Discontinued Study Medication Due to AEs During the Treatment Period and First 14 Follow-up Days | Treatment period plus the first 14 days of follow-up (up to 50 weeks) | An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. 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 Sustained Virologic Response 24 Weeks After the End of Study Therapy (SVR24) | 24 weeks after the end of all treatment (up to 72 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 9.3 IU/mL (in plasma). SVR24 was defined as undetectable (TND) HCV RNA at 24 weeks after the end of all study therapy. 95% confidence intervals provided based on the Clopper-Pearson method. |
| Median Time to First Achievement of Undetectable HCV RNA During Treatment | From first dose of study medication until first achievement of undetectable HCV RNA (up to 48 weeks of treatment) | 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. Undetectable HCV RNA (target not detected \[TND\]) was defined as below the 9.3 IU/ml limit of detection. Kaplan Meier summary statistics were calculated for each treatment arm. |
| Percentage of Participants Achieving Undetectable HCV RNA at Week 72 | Week 72 | 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. Undetectable HCV RNA (target not detected \[TND\]) was defined as below the 9.3 IU/ml limit of detection. 95% confidence intervals provided based on the Clopper-Pearson method. |
| Percentage of Participants Achieving Rapid Viral Response (RVR) | After 4 weeks of treatment with grazoprevir/boceprevir | 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 9.3 IU/mL (in plasma). RVR was defined as undetectable (TND) HCV RNA at Week 4 of study therapy. 95% confidence intervals provided based on the Clopper-Pearson method. |
| Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of Study Therapy (SVR12) | 12 weeks after the end of all treatment (up to 60 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 9.3 IU/mL (in plasma). SVR12 was defined as undetectable (TND) HCV RNA at 12 weeks after the end of all study therapy. 95% confidence intervals provided based on the Clopper-Pearson method. |
Participant flow
Pre-assignment details
368 participants enrolled on study. 36 cirrhotic participants received open-label (OL) grazoprevir + peginterferon (Peg-IFN) + ribavirin (RBV), and 332 non-cirrhotic participants were randomized to receive 100, 200, 400, or 800 mg grazoprevir + Peg-IFN + RBV. 43 in the 400 mg group and 36 in the 800 mg group were down-dosed to 100 mg grazoprevir.
Participants by arm
| Arm | Count |
|---|---|
| OL Grazoprevir 100 mg Treatment-naïve (TN) cirrhotic participants received open-label Grazoprevir 100 mg + Peg-IFN + RBV for 12 weeks followed by 12 or 36 weeks of Peg-IFN + RBV, based on response guided therapy. | 36 |
| Grazoprevir 100 mg TN NC participants received Grazoprevir 100 mg + Peg-IFN + RBV for 12 weeks followed by 12 or 36 weeks of Peg-IFN + RBV, based on response guided therapy. | 66 |
| Grazoprevir 200 mg TN NC participants received Grazoprevir 200 mg + Peg-IFN + RBV for 12 weeks followed by 12 or 36 weeks of Peg-IFN + RBV, based on response guided therapy. | 68 |
| Grazoprevir 400 mg TN NC participants received Grazoprevir 400 mg + Peg-IFN + RBV for 12 weeks followed by 12 or 36 weeks of Peg-IFN + RBV, based on response guided therapy. | 24 |
| Grazoprevir 800 mg TN NC participants received Grazoprevir 800 mg + Peg-IFN + RBV for 12 weeks followed by 12 or 36 weeks of Peg-IFN + RBV, based on response guided therapy. | 29 |
| Grazoprevir 400 mg/100 mg TN NC participants initially were randomized to receive Grazoprevir 400 mg + Peg-IFN + RBV for 12 weeks followed by 12 or 36 weeks of Peg-IFN + RBV, based on response guided therapy. As the result of an interim analysis, these participants were unblinded and transitioned to 100 mg grazoprevir once daily + Peg-IFN + RBV for 12 weeks followed by 12 or 36 weeks of Peg-IFN + RBV, based on response guided therapy. | 43 |
| Grazoprevir 800 mg/100 mg TN NC participants initially were randomized to receive Grazoprevir 800 mg + Peg-IFN + RBV for 12 weeks followed by 12 or 36 weeks of Peg-IFN + RBV, based on response guided therapy. As the result of an interim analysis, these participants were unblinded and transitioned to 100 mg grazoprevir once daily + Peg-IFN + RBV for 12 weeks followed by 12 or 36 weeks of Peg-IFN + RBV, based on response guided therapy. | 36 |
| Boceprevir 800 mg TN NC participants started a 4 week lead-in with Peg-IFN + RBV, then received Boceprevir 800 mg + Peg-IFN + RBV for 24 weeks followed by 0 or 20 weeks of Peg-IFN + RBV, based on response guided therapy. | 66 |
| Total | 368 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 6 | 4 | 0 | 4 | 4 | 3 | 6 |
| Overall Study | Status Not Recorded | 4 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 3 | 4 | 2 | 2 | 3 | 3 | 9 |
Baseline characteristics
| Characteristic | OL Grazoprevir 100 mg | Grazoprevir 100 mg | Grazoprevir 200 mg | Grazoprevir 400 mg | Grazoprevir 800 mg | Grazoprevir 400 mg/100 mg | Grazoprevir 800 mg/100 mg | Boceprevir 800 mg | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 54.4 years STANDARD_DEVIATION 6.9 | 46.4 years STANDARD_DEVIATION 11.3 | 48.3 years STANDARD_DEVIATION 10.6 | 44.6 years STANDARD_DEVIATION 12.5 | 50.4 years STANDARD_DEVIATION 13.4 | 48.3 years STANDARD_DEVIATION 11.4 | 50.3 years STANDARD_DEVIATION 11.2 | 48.3 years STANDARD_DEVIATION 11.2 | 48.7 years STANDARD_DEVIATION 11.2 |
| Sex: Female, Male Female | 14 Participants | 25 Participants | 32 Participants | 12 Participants | 15 Participants | 15 Participants | 13 Participants | 29 Participants | 155 Participants |
| Sex: Female, Male Male | 22 Participants | 41 Participants | 36 Participants | 12 Participants | 14 Participants | 28 Participants | 23 Participants | 37 Participants | 213 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 |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 34 / 36 | 64 / 66 | 65 / 68 | 23 / 24 | 27 / 29 | 42 / 43 | 36 / 36 | 64 / 66 |
| serious Total, serious adverse events | 3 / 36 | 6 / 66 | 9 / 68 | 2 / 24 | 2 / 29 | 5 / 43 | 4 / 36 | 5 / 66 |
Outcome results
Primary
Number of Participants Experiencing Adverse Events (AEs) During the Treatment Period and First 14 Follow-up Days
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. 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: Treatment period plus the first 14 days of follow-up (up to 50 weeks)
Population: All Participants as Treated (APaT) population; all randomized/enrolled who received ≥1 dose of study treatment according to treatment actually received. Participants who received grazoprevir 400 or 800 mg and were then down-dosed to receive grazoprevir 100 mg are reported separately from participants who completed the 400 mg and 800 mg regimens.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OL Grazoprevir 100 mg | Number of Participants Experiencing Adverse Events (AEs) During the Treatment Period and First 14 Follow-up Days | 34 participants |
| Grazoprevir 100 mg | Number of Participants Experiencing Adverse Events (AEs) During the Treatment Period and First 14 Follow-up Days | 65 participants |
| Grazoprevir 200 mg | Number of Participants Experiencing Adverse Events (AEs) During the Treatment Period and First 14 Follow-up Days | 66 participants |
| Grazoprevir 400 mg | Number of Participants Experiencing Adverse Events (AEs) During the Treatment Period and First 14 Follow-up Days | 23 participants |
| Grazoprevir 800 mg | Number of Participants Experiencing Adverse Events (AEs) During the Treatment Period and First 14 Follow-up Days | 28 participants |
| Grazoprevir 400 mg/100 mg | Number of Participants Experiencing Adverse Events (AEs) During the Treatment Period and First 14 Follow-up Days | 42 participants |
| Grazoprevir 800 mg/100 mg | Number of Participants Experiencing Adverse Events (AEs) During the Treatment Period and First 14 Follow-up Days | 35 participants |
| Boceprevir 800 mg | Number of Participants Experiencing Adverse Events (AEs) During the Treatment Period and First 14 Follow-up Days | 64 participants |
Primary
Number of Participants Who Discontinued Study Medication Due to AEs During the Treatment Period and First 14 Follow-up Days
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. 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: Treatment period plus the first 14 days of follow-up (up to 50 weeks)
Population: APaT population; all randomized/enrolled who received ≥1 dose of study treatment according to treatment actually received. Participants who received grazoprevir 400 or 800 mg and were then down-dosed to receive grazoprevir 100 mg are reported separately from participants who completed the 400 mg and 800 mg regimens.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OL Grazoprevir 100 mg | Number of Participants Who Discontinued Study Medication Due to AEs During the Treatment Period and First 14 Follow-up Days | 2 participants |
| Grazoprevir 100 mg | Number of Participants Who Discontinued Study Medication Due to AEs During the Treatment Period and First 14 Follow-up Days | 3 participants |
| Grazoprevir 200 mg | Number of Participants Who Discontinued Study Medication Due to AEs During the Treatment Period and First 14 Follow-up Days | 4 participants |
| Grazoprevir 400 mg | Number of Participants Who Discontinued Study Medication Due to AEs During the Treatment Period and First 14 Follow-up Days | 2 participants |
| Grazoprevir 800 mg | Number of Participants Who Discontinued Study Medication Due to AEs During the Treatment Period and First 14 Follow-up Days | 3 participants |
| Grazoprevir 400 mg/100 mg | Number of Participants Who Discontinued Study Medication Due to AEs During the Treatment Period and First 14 Follow-up Days | 4 participants |
| Grazoprevir 800 mg/100 mg | Number of Participants Who Discontinued Study Medication Due to AEs During the Treatment Period and First 14 Follow-up Days | 2 participants |
| Boceprevir 800 mg | Number of Participants Who Discontinued Study Medication Due to AEs During the Treatment Period and First 14 Follow-up Days | 9 participants |
Primary
Percentage of Participants Achieving Complete Early Viral Response (cEVR)
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 9.3 IU/mL (in plasma). cEVR was defined as undetectable HCV RNA (target not detected \[TND\]) at Week 12. 95% confidence intervals provided based on the Clopper-Pearson method.
Time frame: After 12 weeks of treatment with grazoprevir/boceprevir
Population: FAS; all randomized/enrolled participants who received ≥1 dose of study treatment. A Missing = Failure approach was used for missing data. Results for participants who received grazoprevir 400 or 800 mg and were then down-dosed to receive grazoprevir 100 mg are reported separately from participants who completed the 400 mg and 800 mg regimens.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OL Grazoprevir 100 mg | Percentage of Participants Achieving Complete Early Viral Response (cEVR) | 94.4 percentage of participants |
| Grazoprevir 100 mg | Percentage of Participants Achieving Complete Early Viral Response (cEVR) | 80.3 percentage of participants |
| Grazoprevir 200 mg | Percentage of Participants Achieving Complete Early Viral Response (cEVR) | 85.3 percentage of participants |
| Grazoprevir 400 mg | Percentage of Participants Achieving Complete Early Viral Response (cEVR) | 87.5 percentage of participants |
| Grazoprevir 800 mg | Percentage of Participants Achieving Complete Early Viral Response (cEVR) | 75.9 percentage of participants |
| Grazoprevir 400 mg/100 mg | Percentage of Participants Achieving Complete Early Viral Response (cEVR) | 86.0 percentage of participants |
| Grazoprevir 800 mg/100 mg | Percentage of Participants Achieving Complete Early Viral Response (cEVR) | 86.1 percentage of participants |
| Boceprevir 800 mg | Percentage of Participants Achieving Complete Early Viral Response (cEVR) | 69.7 percentage of participants |
Secondary
Median Time to First Achievement of Undetectable HCV RNA During Treatment
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. Undetectable HCV RNA (target not detected \[TND\]) was defined as below the 9.3 IU/ml limit of detection. Kaplan Meier summary statistics were calculated for each treatment arm.
Time frame: From first dose of study medication until first achievement of undetectable HCV RNA (up to 48 weeks of treatment)
Population: FAS; all randomized/enrolled participants who received ≥1 dose of study treatment. Results for participants who received grazoprevir 400 or 800 mg and were then down-dosed to receive grazoprevir 100 mg are reported separately from participants who completed the 400 mg and 800 mg regimens. Participants in the FAS not achieving TND were censored.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| OL Grazoprevir 100 mg | Median Time to First Achievement of Undetectable HCV RNA During Treatment | 22.0 days |
| Grazoprevir 100 mg | Median Time to First Achievement of Undetectable HCV RNA During Treatment | 15.0 days |
| Grazoprevir 200 mg | Median Time to First Achievement of Undetectable HCV RNA During Treatment | 28.0 days |
| Grazoprevir 400 mg | Median Time to First Achievement of Undetectable HCV RNA During Treatment | 16.0 days |
| Grazoprevir 800 mg | Median Time to First Achievement of Undetectable HCV RNA During Treatment | 16.5 days |
| Grazoprevir 400 mg/100 mg | Median Time to First Achievement of Undetectable HCV RNA During Treatment | 27.0 days |
| Grazoprevir 800 mg/100 mg | Median Time to First Achievement of Undetectable HCV RNA During Treatment | 29.0 days |
| Boceprevir 800 mg | Median Time to First Achievement of Undetectable HCV RNA During Treatment | 57.0 days |
Secondary
Percentage of Participants Achieving Rapid Viral Response (RVR)
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 9.3 IU/mL (in plasma). RVR was defined as undetectable (TND) HCV RNA at Week 4 of study therapy. 95% confidence intervals provided based on the Clopper-Pearson method.
Time frame: After 4 weeks of treatment with grazoprevir/boceprevir
Population: FAS; all randomized/enrolled participants who received ≥1 dose of study treatment. A Missing = Failure approach was used for missing data. Results for participants who received grazoprevir 400 or 800 mg and were then down-dosed to receive grazoprevir 100 mg are reported separately from participants who completed the 400 mg and 800 mg regimens.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OL Grazoprevir 100 mg | Percentage of Participants Achieving Rapid Viral Response (RVR) | 72.2 percentage of participants |
| Grazoprevir 100 mg | Percentage of Participants Achieving Rapid Viral Response (RVR) | 90.9 percentage of participants |
| Grazoprevir 200 mg | Percentage of Participants Achieving Rapid Viral Response (RVR) | 91.2 percentage of participants |
| Grazoprevir 400 mg | Percentage of Participants Achieving Rapid Viral Response (RVR) | 87.5 percentage of participants |
| Grazoprevir 800 mg | Percentage of Participants Achieving Rapid Viral Response (RVR) | 86.2 percentage of participants |
| Grazoprevir 400 mg/100 mg | Percentage of Participants Achieving Rapid Viral Response (RVR) | 81.4 percentage of participants |
| Grazoprevir 800 mg/100 mg | Percentage of Participants Achieving Rapid Viral Response (RVR) | 83.3 percentage of participants |
| Boceprevir 800 mg | Percentage of Participants Achieving Rapid Viral Response (RVR) | 59.1 percentage of participants |
Secondary
Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of 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 9.3 IU/mL (in plasma). SVR12 was defined as undetectable (TND) HCV RNA 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 the end of all treatment (up to 60 weeks)
Population: FAS; all randomized/enrolled participants who received ≥1 dose of study treatment. A Missing = Failure approach was used for missing data. Results for participants who received grazoprevir 400 or 800 mg and were then down-dosed to receive grazoprevir 100 mg are reported separately from participants who completed the 400 mg and 800 mg regimens.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OL Grazoprevir 100 mg | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of Study Therapy (SVR12) | 72.2 percentage of participants |
| Grazoprevir 100 mg | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of Study Therapy (SVR12) | 89.4 percentage of participants |
| Grazoprevir 200 mg | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of Study Therapy (SVR12) | 91.2 percentage of participants |
| Grazoprevir 400 mg | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of Study Therapy (SVR12) | 87.5 percentage of participants |
| Grazoprevir 800 mg | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of Study Therapy (SVR12) | 79.3 percentage of participants |
| Grazoprevir 400 mg/100 mg | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of Study Therapy (SVR12) | 93.0 percentage of participants |
| Grazoprevir 800 mg/100 mg | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of Study Therapy (SVR12) | 91.7 percentage of participants |
| Boceprevir 800 mg | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of Study Therapy (SVR12) | 60.6 percentage of participants |
Secondary
Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of 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 lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL (in plasma). SVR24 was defined as undetectable (TND) HCV RNA 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 the end of all treatment (up to 72 weeks)
Population: FAS; all randomized/enrolled participants who received ≥1 dose of study treatment. A Missing = Failure approach was used for missing data. Results for participants who received grazoprevir 400 or 800 mg and were then down-dosed to receive grazoprevir 100 mg are reported separately from participants who completed the 400 mg and 800 mg regimens.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OL Grazoprevir 100 mg | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of Study Therapy (SVR24) | 72.2 percentage of participants |
| Grazoprevir 100 mg | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of Study Therapy (SVR24) | 86.4 percentage of participants |
| Grazoprevir 200 mg | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of Study Therapy (SVR24) | 92.6 percentage of participants |
| Grazoprevir 400 mg | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of Study Therapy (SVR24) | 87.5 percentage of participants |
| Grazoprevir 800 mg | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of Study Therapy (SVR24) | 79.3 percentage of participants |
| Grazoprevir 400 mg/100 mg | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of Study Therapy (SVR24) | 93.0 percentage of participants |
| Grazoprevir 800 mg/100 mg | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of Study Therapy (SVR24) | 91.7 percentage of participants |
| Boceprevir 800 mg | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of Study Therapy (SVR24) | 57.6 percentage of participants |
Secondary
Percentage of Participants Achieving Undetectable HCV RNA at Week 72
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. Undetectable HCV RNA (target not detected \[TND\]) was defined as below the 9.3 IU/ml limit of detection. 95% confidence intervals provided based on the Clopper-Pearson method.
Time frame: Week 72
Population: FAS; all randomized/enrolled participants who received ≥1 dose of study treatment. A Missing = Failure approach was used for missing data. Results for participants who received grazoprevir 400 or 800 mg and were then down-dosed to receive grazoprevir 100 mg are reported separately from participants who completed the 400 mg and 800 mg regimens.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OL Grazoprevir 100 mg | Percentage of Participants Achieving Undetectable HCV RNA at Week 72 | 69.4 percentage of participants |
| Grazoprevir 100 mg | Percentage of Participants Achieving Undetectable HCV RNA at Week 72 | 80.3 percentage of participants |
| Grazoprevir 200 mg | Percentage of Participants Achieving Undetectable HCV RNA at Week 72 | 86.8 percentage of participants |
| Grazoprevir 400 mg | Percentage of Participants Achieving Undetectable HCV RNA at Week 72 | 87.5 percentage of participants |
| Grazoprevir 800 mg | Percentage of Participants Achieving Undetectable HCV RNA at Week 72 | 75.9 percentage of participants |
| Grazoprevir 400 mg/100 mg | Percentage of Participants Achieving Undetectable HCV RNA at Week 72 | 79.1 percentage of participants |
| Grazoprevir 800 mg/100 mg | Percentage of Participants Achieving Undetectable HCV RNA at Week 72 | 83.3 percentage of participants |
| Boceprevir 800 mg | Percentage of Participants Achieving Undetectable HCV RNA at Week 72 | 54.5 percentage of participants |