Hepatitis C, Chronic
Conditions
Brief summary
The purpose of this study is to estimate the difference in the efficacy between a 16-week treatment regimen of boceprevir (BOC) in combination with peg-intron alpha 2b (P) plus ribavirin (R) (BOC + PR) and a 28-week treatment regimen of BOC + PR in previously untreated participants with chronic hepatitis C (CHC) genotype 1 in Asia who achieve undetectable hepatitis C virus ribonucleic acid (HCV RNA).
Interventions
DRUGBoceprevir
800 mg three times daily orally
BIOLOGICALPeg-interferon alfa-2b
1.5 mcg/kg weekly subcutaneously
DRUGRibavirin
800-1400 mg twice-daily divided orally based on body weight
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* weigh ≥ 40 kg and ≤ 125 kg * have CHC genotype 1 infection * has had a liver biopsy or non-invasive liver fibrosis test that shows no evidence of cirrhosis and hepatocellular carcinoma * must agree that the participant and the participant's partner will each use acceptable methods of contraception for at least 2 weeks prior to Day 1 and continue until at least 6 months after last dose of study medication, or longer if dictated by local regulations (for a female participant who is of childbearing potential or male participant with female sexual partner who is of childbearing potential)
Exclusion criteria
* participates in any other interventional clinical trial within 30 days of the screening visit in this trial or intends to participate in another interventional clinical trial during participation in this trial * is co-infected with human immunodeficiency virus (HIV) or hepatitis B virus * has evidence or history of chronic hepatitis not caused by HCV, including but not limited to nonalcoholic steatohepatitis (NASH), drug-induced hepatitis, and autoimmune hepatitis * has evidence of decompensated liver disease including, but not limited to, a history or presence of clinical ascites, bleeding varices, or hepatic encephalopathy * has evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC * has evidence of active or suspected malignancy, or a history of malignancy, within the last 5 years * has been previously treated with an interferon or ribavirin regimen or HCV direct acting anti-viral regimen, or treated for hepatitis C with any investigational medication * taking/plans to take significant inducers of inhibitors of Cytochrome P450 3A4 (CYP3A4) substrates 2 weeks prior to start of study medications, or herbal supplements, including but not limited to St. John's Wort 2 weeks prior to start of study medications (Day 1) * has pre-existing psychiatric condition(s) * has a clinical diagnosis of substance abuse * has any known medical condition that could interfere with the participation in and completion of the trial including immunologically-mediated disease, chronic pulmonary disease, or current or history of any clinically significant cardiac abnormalities/dysfunction * is pregnant or nursing (for female participant) or female partner intends to become pregnant (for male participant)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Undetectable HCV RNA Who Achieve Sustained Viral Response at Follow-up Week 12 (SVR12) [16-Week Arm vs. 28-Week Arm] | Follow-up Week (FW) 12 (up to 40 weeks) | SVR12 was declared when participants who had undetectable HCV RNA (HCV RNA \< Lower Limit of Quantification \[LLoQ\]) after the 12-week lead-in also had undetectable HCV RNA 12 weeks after completing their assigned BOC treatment regimen. The Roche COBAS™ Taqman™ automated HCV test (v2.0 assay) used in this study has a LLoQ of 15 IU/mL. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving SVR12 Among Participants With Undetectable HCV RNA Across Treatment | TW4, TW8, and TW12 | The percentage of participants achieving SVR12 who had undetectable HCV RNA (HCV RNA \<LLoQ) at Week 4, Week 8, and Week 12 is summarized for each arm. The Roche COBAS™ Taqman™ automated HCV test (v2.0 assay) used in this study has a LLoQ of 15 IU/mL. |
| Percentage of Participants With Relapse | From EOT to FW12 (up to 12 weeks) | The percentage of viral relapse (defined as confirmed HCV RNA \>15 IU/mL after End-of-Treatment \[EOT\]) among participants who had undetectable HCV RNA at EOT was determined for each arm. The Roche COBAS™ Taqman™ automated HCV test (v2.0 assay) used in this study has a LLoQ of 15 IU/mL. |
| Percentage of Participants With Neutropenia | Up to 60 weeks | The percentage of participants with neutropenia (neutrophil count \<0.75 x10\^9/L) is summarized for each arm. |
| Percentage of Participants With Undetectable HCV RNA Across Treatment | TW4, TW8, and TW12 | The percentage of participants with undetectable HCV RNA (HCV RNA \<LLoQ) at TW4, TW8, and TW12 is summarized for each arm. The Roche COBAS™ Taqman™ automated HCV test (v2.0 assay) used in this study has a LLoQ of 15 IU/mL. |
| Percentage of Participants With Dose Discontinuation Due to Adverse Events (AEs) | From TW1 through TW48 | An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The percentage of participants who discontinued from BOC, BOC + RBV, or all medications due to an AE are reported. |
| Percentage of Participants With Treatment-Related Serious AEs (SAEs) | Up to 60 weeks | A SAE is any AE that results in death, is life threatening, results in persistent or significant disability, results in or prolongs an existing inpatient hospitalization, is a congenital birth defect, is a cancer, is associated with an overdose, or is another important medical event. |
| Percentage of Participants With Anemia | Up to 60 weeks | The percentage of participants with anemia (hemoglobin \[Hgb\] \<10 g/dL) was determined in each arm. |
Participant flow
Recruitment details
Treatment-naïve adult male and female participants with chronic hepatitis C virus (HCV) genotype 1 (GT1) infection were recruited in the Asia-Pacific region.
Participants by arm
| Arm | Count |
|---|---|
| Arm 1: 16-week Treatment Arm After completing the 12-week lead-in, participants with undetectable HCV RNA were randomized to receive an additional 4 weeks of BOC + PR, for a total of 16 weeks of treatment. At Week 16, participants underwent 12 weeks of follow-up (participation complete at Week 28). | 102 |
| Arm 2: 28-week Treatment Arm After completing the 12-week lead-in, participants with undetectable HCV RNA were randomized to receive an additional 16 weeks of BOC + PR, for a total of 28 weeks of treatment. At Week 28, participants underwent 12 weeks of follow-up (participation complete at Week 40). | 105 |
| Arm 3: 48-week Treatment Arm After completing the 12-week lead-in, participants with detectable HCV RNA were allocated to receive an additional 24 weeks of BOC + PR and an additional 12 weeks of PR, for a total of 48 weeks of treatment. At Week 48, participants underwent 12 weeks of follow-up (participation complete at Week 60). | 50 |
| Total | 257 |
Baseline characteristics
| Characteristic | Arm 1: 16-week Treatment Arm | Arm 2: 28-week Treatment Arm | Arm 3: 48-week Treatment Arm | Total |
|---|---|---|---|---|
| Age, Continuous | 44.1 Years STANDARD_DEVIATION 11.1 | 44.6 Years STANDARD_DEVIATION 10.6 | 46.5 Years STANDARD_DEVIATION 11.8 | 44.8 Years STANDARD_DEVIATION 11 |
| Sex: Female, Male Female | 43 Participants | 41 Participants | 24 Participants | 108 Participants |
| Sex: Female, Male Male | 59 Participants | 64 Participants | 26 Participants | 149 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 96 / 102 | 98 / 105 | 46 / 50 |
| serious Total, serious adverse events | 9 / 102 | 6 / 105 | 4 / 50 |
Outcome results
Primary
Percentage of Participants With Undetectable HCV RNA Who Achieve Sustained Viral Response at Follow-up Week 12 (SVR12) [16-Week Arm vs. 28-Week Arm]
SVR12 was declared when participants who had undetectable HCV RNA (HCV RNA \< Lower Limit of Quantification \[LLoQ\]) after the 12-week lead-in also had undetectable HCV RNA 12 weeks after completing their assigned BOC treatment regimen. The Roche COBAS™ Taqman™ automated HCV test (v2.0 assay) used in this study has a LLoQ of 15 IU/mL.
Time frame: Follow-up Week (FW) 12 (up to 40 weeks)
Population: Participants of the Full Analysis Set (FAS) who were treated with any study medication, had undetectable HCV RNA at TW8, and were randomized to Arm 1 or Arm 2. Participants in Arm 3 were not included in the primary efficacy analysis as pre-specified by the protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: 16-week Treatment Arm | Percentage of Participants With Undetectable HCV RNA Who Achieve Sustained Viral Response at Follow-up Week 12 (SVR12) [16-Week Arm vs. 28-Week Arm] | 70.6 Percentage of Participants |
| Arm 2: 28-week Treatment Arm | Percentage of Participants With Undetectable HCV RNA Who Achieve Sustained Viral Response at Follow-up Week 12 (SVR12) [16-Week Arm vs. 28-Week Arm] | 81.9 Percentage of Participants |
95% CI: [-23.2, 0.4]
Secondary
Percentage of Participants Achieving SVR12 Among Participants With Undetectable HCV RNA Across Treatment
The percentage of participants achieving SVR12 who had undetectable HCV RNA (HCV RNA \<LLoQ) at Week 4, Week 8, and Week 12 is summarized for each arm. The Roche COBAS™ Taqman™ automated HCV test (v2.0 assay) used in this study has a LLoQ of 15 IU/mL.
Time frame: TW4, TW8, and TW12
Population: The subset of the FAS population consisting of all participants treated with any study medication in Arms 1, 2, and 3 and who had undetectable HCV RNA at Week 4, Week 8, or Week 12.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 1: 16-week Treatment Arm | Percentage of Participants Achieving SVR12 Among Participants With Undetectable HCV RNA Across Treatment | % Undetectable HCV RNA at TW8 (n=101, 104, 0) | 69.6 Percentage of Participants |
| Arm 1: 16-week Treatment Arm | Percentage of Participants Achieving SVR12 Among Participants With Undetectable HCV RNA Across Treatment | % Undetectable HCV RNA at TW4 (n=25, 18, 0) | 24.5 Percentage of Participants |
| Arm 1: 16-week Treatment Arm | Percentage of Participants Achieving SVR12 Among Participants With Undetectable HCV RNA Across Treatment | % Undetectable HCV RNA at TW12 (n=100, 103, 20) | 68.6 Percentage of Participants |
| Arm 2: 28-week Treatment Arm | Percentage of Participants Achieving SVR12 Among Participants With Undetectable HCV RNA Across Treatment | % Undetectable HCV RNA at TW8 (n=101, 104, 0) | 81.0 Percentage of Participants |
| Arm 2: 28-week Treatment Arm | Percentage of Participants Achieving SVR12 Among Participants With Undetectable HCV RNA Across Treatment | % Undetectable HCV RNA at TW4 (n=25, 18, 0) | 14.3 Percentage of Participants |
| Arm 2: 28-week Treatment Arm | Percentage of Participants Achieving SVR12 Among Participants With Undetectable HCV RNA Across Treatment | % Undetectable HCV RNA at TW12 (n=100, 103, 20) | 80.0 Percentage of Participants |
| Arm 3: 48-week Treatment Arm | Percentage of Participants Achieving SVR12 Among Participants With Undetectable HCV RNA Across Treatment | % Undetectable HCV RNA at TW4 (n=25, 18, 0) | 0.0 Percentage of Participants |
| Arm 3: 48-week Treatment Arm | Percentage of Participants Achieving SVR12 Among Participants With Undetectable HCV RNA Across Treatment | % Undetectable HCV RNA at TW12 (n=100, 103, 20) | 41.4 Percentage of Participants |
| Arm 3: 48-week Treatment Arm | Percentage of Participants Achieving SVR12 Among Participants With Undetectable HCV RNA Across Treatment | % Undetectable HCV RNA at TW8 (n=101, 104, 0) | 0.0 Percentage of Participants |
Secondary
Percentage of Participants With Anemia
The percentage of participants with anemia (hemoglobin \[Hgb\] \<10 g/dL) was determined in each arm.
Time frame: Up to 60 weeks
Population: The All Participants as Treated (APaT) includes all participants who received ≥1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: 16-week Treatment Arm | Percentage of Participants With Anemia | 33.3 Percentage of Participants |
| Arm 2: 28-week Treatment Arm | Percentage of Participants With Anemia | 43.8 Percentage of Participants |
| Arm 3: 48-week Treatment Arm | Percentage of Participants With Anemia | 26.0 Percentage of Participants |
Secondary
Percentage of Participants With Dose Discontinuation Due to Adverse Events (AEs)
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The percentage of participants who discontinued from BOC, BOC + RBV, or all medications due to an AE are reported.
Time frame: From TW1 through TW48
Population: The APaT includes all participants who received ≥1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 1: 16-week Treatment Arm | Percentage of Participants With Dose Discontinuation Due to Adverse Events (AEs) | Discontinued from BOC + R | 0.0 Percentage of Participants |
| Arm 1: 16-week Treatment Arm | Percentage of Participants With Dose Discontinuation Due to Adverse Events (AEs) | Discontinued from BOC | 2.9 Percentage of Participants |
| Arm 1: 16-week Treatment Arm | Percentage of Participants With Dose Discontinuation Due to Adverse Events (AEs) | Discontinued from all Study Medication | 0.0 Percentage of Participants |
| Arm 2: 28-week Treatment Arm | Percentage of Participants With Dose Discontinuation Due to Adverse Events (AEs) | Discontinued from BOC + R | 5.7 Percentage of Participants |
| Arm 2: 28-week Treatment Arm | Percentage of Participants With Dose Discontinuation Due to Adverse Events (AEs) | Discontinued from BOC | 7.6 Percentage of Participants |
| Arm 2: 28-week Treatment Arm | Percentage of Participants With Dose Discontinuation Due to Adverse Events (AEs) | Discontinued from all Study Medication | 5.7 Percentage of Participants |
| Arm 3: 48-week Treatment Arm | Percentage of Participants With Dose Discontinuation Due to Adverse Events (AEs) | Discontinued from BOC | 16.0 Percentage of Participants |
| Arm 3: 48-week Treatment Arm | Percentage of Participants With Dose Discontinuation Due to Adverse Events (AEs) | Discontinued from all Study Medication | 8.0 Percentage of Participants |
| Arm 3: 48-week Treatment Arm | Percentage of Participants With Dose Discontinuation Due to Adverse Events (AEs) | Discontinued from BOC + R | 8.0 Percentage of Participants |
Secondary
Percentage of Participants With Neutropenia
The percentage of participants with neutropenia (neutrophil count \<0.75 x10\^9/L) is summarized for each arm.
Time frame: Up to 60 weeks
Population: The All Participants as Treated (APaT) includes all participants who received ≥1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: 16-week Treatment Arm | Percentage of Participants With Neutropenia | 10.8 Percentage of Participants |
| Arm 2: 28-week Treatment Arm | Percentage of Participants With Neutropenia | 12.4 Percentage of Participants |
| Arm 3: 48-week Treatment Arm | Percentage of Participants With Neutropenia | 4.0 Percentage of Participants |
Secondary
Percentage of Participants With Relapse
The percentage of viral relapse (defined as confirmed HCV RNA \>15 IU/mL after End-of-Treatment \[EOT\]) among participants who had undetectable HCV RNA at EOT was determined for each arm. The Roche COBAS™ Taqman™ automated HCV test (v2.0 assay) used in this study has a LLoQ of 15 IU/mL.
Time frame: From EOT to FW12 (up to 12 weeks)
Population: Participants in the FAS with undetectable HCV RNA at EOT and who have data available at FW12 were included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: 16-week Treatment Arm | Percentage of Participants With Relapse | 20.4 Percentage of Participants |
| Arm 2: 28-week Treatment Arm | Percentage of Participants With Relapse | 1.1 Percentage of Participants |
| Arm 3: 48-week Treatment Arm | Percentage of Participants With Relapse | 0.0 Percentage of Participants |
Secondary
Percentage of Participants With Treatment-Related Serious AEs (SAEs)
A SAE is any AE that results in death, is life threatening, results in persistent or significant disability, results in or prolongs an existing inpatient hospitalization, is a congenital birth defect, is a cancer, is associated with an overdose, or is another important medical event.
Time frame: Up to 60 weeks
Population: The APaT includes all participants who received ≥1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: 16-week Treatment Arm | Percentage of Participants With Treatment-Related Serious AEs (SAEs) | 2.9 Percentage of Participants |
| Arm 2: 28-week Treatment Arm | Percentage of Participants With Treatment-Related Serious AEs (SAEs) | 3.8 Percentage of Participants |
| Arm 3: 48-week Treatment Arm | Percentage of Participants With Treatment-Related Serious AEs (SAEs) | 4.0 Percentage of Participants |
Secondary
Percentage of Participants With Undetectable HCV RNA Across Treatment
The percentage of participants with undetectable HCV RNA (HCV RNA \<LLoQ) at TW4, TW8, and TW12 is summarized for each arm. The Roche COBAS™ Taqman™ automated HCV test (v2.0 assay) used in this study has a LLoQ of 15 IU/mL.
Time frame: TW4, TW8, and TW12
Population: Participants in the FAS population (consisting of all participants treated with any study medication who had undetectable HCV RNA at TW8 and were randomized to Arm 1 or Arm 2, and participants with detectable HCV RNA at TW8 in Arm 3) with available data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 1: 16-week Treatment Arm | Percentage of Participants With Undetectable HCV RNA Across Treatment | TW8 | 100.0 Percentage of Participants |
| Arm 1: 16-week Treatment Arm | Percentage of Participants With Undetectable HCV RNA Across Treatment | TW4 | 24.8 Percentage of Participants |
| Arm 1: 16-week Treatment Arm | Percentage of Participants With Undetectable HCV RNA Across Treatment | TW12 | 99.0 Percentage of Participants |
| Arm 2: 28-week Treatment Arm | Percentage of Participants With Undetectable HCV RNA Across Treatment | TW8 | 100.0 Percentage of Participants |
| Arm 2: 28-week Treatment Arm | Percentage of Participants With Undetectable HCV RNA Across Treatment | TW4 | 17.1 Percentage of Participants |
| Arm 2: 28-week Treatment Arm | Percentage of Participants With Undetectable HCV RNA Across Treatment | TW12 | 100.0 Percentage of Participants |
| Arm 3: 48-week Treatment Arm | Percentage of Participants With Undetectable HCV RNA Across Treatment | TW4 | 0.0 Percentage of Participants |
| Arm 3: 48-week Treatment Arm | Percentage of Participants With Undetectable HCV RNA Across Treatment | TW12 | 69.0 Percentage of Participants |
| Arm 3: 48-week Treatment Arm | Percentage of Participants With Undetectable HCV RNA Across Treatment | TW8 | 0.0 Percentage of Participants |