Hepatitis C
Conditions
Brief summary
A study to evaluate how effective different levels of Vaniprevir (MK-7009), when administered with Pegylated-Interferon (Peg-IFN) and Ribavirin, are at achieving rapid viral response (RVR) i.e., undetectable hepatitis C virus \[HCV\] viral ribonucleic acid \[RNA\] at Week 4 in participants with chronic HCV infection. The primary hypothesis was that the proportion of participants in one or more of the Vaniprevir treatment groups achieving RVR would be greater than the proportion of placebo participants achieving RVR when Vaniprevir and placebo were co-administered with Peg-IFN/Ribavirin.
Interventions
DRUGComparator: Vaniprevir
Vaniprevir 300 mg b.i.d., 600 mg b.i.d., 600 mg q.d., or 800 mg q.d.; duration of treatment: 28 days
DRUGComparator: Pegylated-Interferon (Peg-IFN)
Peg-IFN 180 mcg once-weekly subcutaneous injection; duration of treatment: 48 weeks
Ribavirin 200 mg tablet b.i.d. (dose based on body weight); duration of treatment: 48 weeks
DRUGComparator: placebo
Matching placebo to vaniprevir; duration of treatment: 28 days
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 65 Years
Healthy volunteers
No
Inclusion criteria
* Patient has chronic Genotype 1 Hepatitis C infection
Exclusion criteria
* Subject has been previously treated for HCV * Has Human Immunodeficiency Virus (HIV) * Has Hepatitis B * Has a history of clinically significant medical condition that may interfere with the study (e.g., stroke or chronic seizures or major neurological disorder) or is contraindicated for treatment with peg-IFN and Ribavirin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving RVR | Week 4 | Rapid Viral Response (RVR) was declared if Hepatitis C Virus (HCV) ribonucleic acid (RNA) was undetectable at Week 4. |
| Number of Participants Experiencing an Adverse Event (AE) | Up to Day 42 | The number of participants experiencing AEs in each treatment group was monitored during the Vaniprevir/Placebo treatment (Day 1 to Day 28) and safety follow-up (Day 29 to Day 42) periods. |
| Number of Participants Discontinuing From Study Therapy Due to AEs | Day 1 to Day 28 | 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 study therapy, whether or not considered related to the use of the product. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With ≥2-log10 Decrease in HCV RNA | Baseline and Week 4 | The number of participants with at least a 2-log10 decrease from baseline in HCV RNA following 4 weeks of treatment with Placebo or Vaniprevir. |
| Number of Participants With ≥3-log10 Decrease in HCV RNA | Baseline and Week 4 | The number of participants with at least a 3-log10 decrease from baseline in HCV RNA following 4 weeks of treatment with Placebo or Vaniprevir. |
| Mean Log Change From Baseline in HCV RNA | Baseline and Week 4 | The mean changes from baseline in log10 HCV RNA in each vaniprevir group was compared against control treatment at Week 4. |
Participant flow
Pre-assignment details
During the double-blind phase (Day 1 to Day 28), participants took Vaniprevir or Placebo in combination with Pegylated Interferon (Peg-IFN)/Ribavirin. During the open-label phase (Day 29 to Week 48), participants took Peg-IFN/Ribavirin only.
Participants by arm
| Arm | Count |
|---|---|
| Placebo + Peg-IFN/Ribavirin Participants took double-blind Placebo + Peg-IFN/Ribavarin from Week 1 to Week 4, followed by open-label Peg-IFN/Ribavarin from Week 5 to Week 48. | 19 |
| Vaniprevir 300 mg b.i.d. + Peg-IFN/Ribavirin Participants took double-blind Vaniprevir 300 mg b.i.d. + Peg-IFN/Ribavarin from Week 1 to Week 4, followed by open-label Peg-IFN/Ribavarin from Week 5 to Week 48. | 18 |
| Vaniprevir 600 mg b.i.d. + Peg-IFN/Ribavirin Participants took double-blind Vaniprevir 600 mg b.i.d. + Peg-IFN/Ribavarin from Week 1 to Week 4, followed by open-label Peg-IFN/Ribavarin from Week 5 to Week 48. | 20 |
| Vaniprevir 600 mg q.d. + Peg-IFN/Ribavirin Participants took double-blind Vaniprevir 600 mg q.d. + Peg-IFN/Ribavarin from Week 1 to Week 4, followed by open-label Peg-IFN/Ribavarin from Week 5 to Week 48. | 18 |
| Vaniprevir 800 mg q.d. + Peg-IFN/Ribavirin Participants took double-blind Vaniprevir 800 mg q.d. + Peg-IFN/Ribavarin from Week 1 to Week 4, followed by open-label Peg-IFN/Ribavarin from Week 5 to Week 48. | 19 |
| Total | 94 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Double-Blind Treatment | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 |
| Open-Label Treatment | Adverse Event | 0 | 0 | 2 | 0 | 1 |
| Open-Label Treatment | Lack of Efficacy | 0 | 2 | 2 | 2 | 1 |
| Open-Label Treatment | Physician Decision | 0 | 0 | 0 | 0 | 1 |
| Open-Label Treatment | Withdrawal by Subject | 1 | 0 | 0 | 3 | 0 |
Baseline characteristics
| Characteristic | Vaniprevir 300 mg b.i.d. + Peg-IFN/Ribavirin | Vaniprevir 600 mg b.i.d. + Peg-IFN/Ribavirin | Vaniprevir 600 mg q.d. + Peg-IFN/Ribavirin | Vaniprevir 800 mg q.d. + Peg-IFN/Ribavirin | Total | Placebo + Peg-IFN/Ribavirin |
|---|---|---|---|---|---|---|
| Age, Continuous | 46.7 Years STANDARD_DEVIATION 10.2 | 42.0 Years STANDARD_DEVIATION 10.7 | 50.1 Years STANDARD_DEVIATION 8.4 | 45.1 Years STANDARD_DEVIATION 12 | 46.2 Years STANDARD_DEVIATION 10.5 | 47.8 Years STANDARD_DEVIATION 10.1 |
| Sex: Female, Male Female | 4 Participants | 9 Participants | 11 Participants | 7 Participants | 39 Participants | 8 Participants |
| Sex: Female, Male Male | 14 Participants | 11 Participants | 7 Participants | 12 Participants | 55 Participants | 11 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 19 / 19 | 16 / 18 | 20 / 20 | 17 / 18 | 18 / 19 |
| serious Total, serious adverse events | 1 / 19 | 3 / 18 | 1 / 20 | 2 / 18 | 2 / 19 |
Outcome results
Primary
Number of Participants Discontinuing From Study Therapy Due to AEs
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 study therapy, whether or not considered related to the use of the product.
Time frame: Day 1 to Day 28
Population: The Safety Population consists of all randomized participants who received at least 1 dose of study therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + Peg-IFN/Ribavirin | Number of Participants Discontinuing From Study Therapy Due to AEs | 0 Participants |
| Vaniprevir 300 mg b.i.d. + Peg-IFN/Ribavirin | Number of Participants Discontinuing From Study Therapy Due to AEs | 0 Participants |
| Vaniprevir 600 mg b.i.d. + Peg-IFN/Ribavirin | Number of Participants Discontinuing From Study Therapy Due to AEs | 0 Participants |
| Vaniprevir 600 mg q.d. + Peg-IFN/Ribavirin | Number of Participants Discontinuing From Study Therapy Due to AEs | 0 Participants |
| Vaniprevir 800 mg q.d. + Peg-IFN/Ribavirin | Number of Participants Discontinuing From Study Therapy Due to AEs | 0 Participants |
Primary
Number of Participants Experiencing an Adverse Event (AE)
The number of participants experiencing AEs in each treatment group was monitored during the Vaniprevir/Placebo treatment (Day 1 to Day 28) and safety follow-up (Day 29 to Day 42) periods.
Time frame: Up to Day 42
Population: The Safety Population consists of all randomized participants who received at least 1 dose of study therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + Peg-IFN/Ribavirin | Number of Participants Experiencing an Adverse Event (AE) | 18 Participants |
| Vaniprevir 300 mg b.i.d. + Peg-IFN/Ribavirin | Number of Participants Experiencing an Adverse Event (AE) | 15 Participants |
| Vaniprevir 600 mg b.i.d. + Peg-IFN/Ribavirin | Number of Participants Experiencing an Adverse Event (AE) | 18 Participants |
| Vaniprevir 600 mg q.d. + Peg-IFN/Ribavirin | Number of Participants Experiencing an Adverse Event (AE) | 16 Participants |
| Vaniprevir 800 mg q.d. + Peg-IFN/Ribavirin | Number of Participants Experiencing an Adverse Event (AE) | 18 Participants |
Primary
Percentage of Participants Achieving RVR
Rapid Viral Response (RVR) was declared if Hepatitis C Virus (HCV) ribonucleic acid (RNA) was undetectable at Week 4.
Time frame: Week 4
Population: The Per Protocol population included all participants who did not have clinically important deviations from protocol-specified criteria. Only participants with an HCV RNA result at the Week 4 time point were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + Peg-IFN/Ribavirin | Percentage of Participants Achieving RVR | 5.6 Percentage of Participants |
| Vaniprevir 300 mg b.i.d. + Peg-IFN/Ribavirin | Percentage of Participants Achieving RVR | 75.0 Percentage of Participants |
| Vaniprevir 600 mg b.i.d. + Peg-IFN/Ribavirin | Percentage of Participants Achieving RVR | 78.9 Percentage of Participants |
| Vaniprevir 600 mg q.d. + Peg-IFN/Ribavirin | Percentage of Participants Achieving RVR | 68.8 Percentage of Participants |
| Vaniprevir 800 mg q.d. + Peg-IFN/Ribavirin | Percentage of Participants Achieving RVR | 83.3 Percentage of Participants |
p-value: <0.00195% CI: [40.3, 86.7]Miettinen and Nurminen method
p-value: <0.00195% CI: [46, 88.6]Miettinen and Nurminen method
p-value: <0.00195% CI: [32.8, 82.7]Miettinen and Nurminen method
p-value: <0.00195% CI: [49.2, 91.3]Miettinen and Nurminen method
Secondary
Mean Log Change From Baseline in HCV RNA
The mean changes from baseline in log10 HCV RNA in each vaniprevir group was compared against control treatment at Week 4.
Time frame: Baseline and Week 4
Population: The Per Protocol population included all participants who did not have clinically important deviations from protocol-specified criteria. Only participants with an HCV RNA result at the Week 4 time point were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + Peg-IFN/Ribavirin | Mean Log Change From Baseline in HCV RNA | -3.6 Log10 IU/mL | Standard Deviation 1.3 |
| Vaniprevir 300 mg b.i.d. + Peg-IFN/Ribavirin | Mean Log Change From Baseline in HCV RNA | -6.1 Log10 IU/mL | Standard Deviation 1.1 |
| Vaniprevir 600 mg b.i.d. + Peg-IFN/Ribavirin | Mean Log Change From Baseline in HCV RNA | -6.3 Log10 IU/mL | Standard Deviation 0.7 |
| Vaniprevir 600 mg q.d. + Peg-IFN/Ribavirin | Mean Log Change From Baseline in HCV RNA | -6.2 Log10 IU/mL | Standard Deviation 0.6 |
| Vaniprevir 800 mg q.d. + Peg-IFN/Ribavirin | Mean Log Change From Baseline in HCV RNA | -6.3 Log10 IU/mL | Standard Deviation 1.4 |
95% CI: [-3.2, -1.8]
95% CI: [-3.4, -2]
95% CI: [-3.4, -2]
95% CI: [-3.3, -2]
Secondary
Number of Participants With ≥2-log10 Decrease in HCV RNA
The number of participants with at least a 2-log10 decrease from baseline in HCV RNA following 4 weeks of treatment with Placebo or Vaniprevir.
Time frame: Baseline and Week 4
Population: The Per Protocol population included all participants who did not have clinically important deviations from protocol-specified criteria. Only participants with an HCV RNA result at the Week 4 time point were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + Peg-IFN/Ribavirin | Number of Participants With ≥2-log10 Decrease in HCV RNA | 16 Number of Participants |
| Vaniprevir 300 mg b.i.d. + Peg-IFN/Ribavirin | Number of Participants With ≥2-log10 Decrease in HCV RNA | 16 Number of Participants |
| Vaniprevir 600 mg b.i.d. + Peg-IFN/Ribavirin | Number of Participants With ≥2-log10 Decrease in HCV RNA | 19 Number of Participants |
| Vaniprevir 600 mg q.d. + Peg-IFN/Ribavirin | Number of Participants With ≥2-log10 Decrease in HCV RNA | 16 Number of Participants |
| Vaniprevir 800 mg q.d. + Peg-IFN/Ribavirin | Number of Participants With ≥2-log10 Decrease in HCV RNA | 17 Number of Participants |
95% CI: [-7.6, 33.2]
95% CI: [-9.7, 33.8]
95% CI: [-16.5, 28.4]
95% CI: [-9.7, 33.8]
Secondary
Number of Participants With ≥3-log10 Decrease in HCV RNA
The number of participants with at least a 3-log10 decrease from baseline in HCV RNA following 4 weeks of treatment with Placebo or Vaniprevir.
Time frame: Baseline and Week 4
Population: The Per Protocol population included all participants who did not have clinically important deviations from protocol-specified criteria. Only participants with an HCV RNA result at the Week 4 time point were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + Peg-IFN/Ribavirin | Number of Participants With ≥3-log10 Decrease in HCV RNA | 15 Number of Participants |
| Vaniprevir 300 mg b.i.d. + Peg-IFN/Ribavirin | Number of Participants With ≥3-log10 Decrease in HCV RNA | 16 Number of Participants |
| Vaniprevir 600 mg b.i.d. + Peg-IFN/Ribavirin | Number of Participants With ≥3-log10 Decrease in HCV RNA | 19 Number of Participants |
| Vaniprevir 600 mg q.d. + Peg-IFN/Ribavirin | Number of Participants With ≥3-log10 Decrease in HCV RNA | 16 Number of Participants |
| Vaniprevir 800 mg q.d. + Peg-IFN/Ribavirin | Number of Participants With ≥3-log10 Decrease in HCV RNA | 17 Number of Participants |
95% CI: [-4, 40.2]
95% CI: [-2.2, 39.5]
95% CI: [-4, 40.2]
95% CI: [-11.4, 34.6]