Hepatitis C, Chronic
Conditions
Brief summary
The primary purpose of this study is to compare the efficacy of two boceprevir (BOC)-containing therapeutic regimens in the treatment of naïve participants with chronic hepatitis C virus (HCV) genotype 1 who have the IL28B CC allele. The regimens differ in the treatment for participants who achieve undetectable HCV ribonucleic acid (RNA) at the end of the peginterferon alfa-2a (peg-IFN) plus ribavirin (RBV) 4 week lead-in. Participants receive either peg-IFN + RBV (Arm 1) or BOC + peg-IFN + RBV (Arm 2). The hypothesis is that Arm 2 is noninferior to Arm 1 in the proportion of participants with undetectable HCV RNA at Follow-Up (FU) Week 24.
Interventions
BIOLOGICALpeg-Interferon alfa-2a
peg-IFN (180 ug) was taken once weekly via subcutaneous injection.
DRUGRibavirin
RBV 200 mg tablets taken by mouth at a total daily dose of 1,000 mg (body weight \<75 kilograms \[kg\]) or 1,200 mg (body weight ≥75 kg) with total daily dose divided into 2 dosings.
DRUGBoceprevir
Four 200 mg BOC capsules taken three times a day by mouth for a total daily dose of 2,400 mg.
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
* Is ≥ 40 kg and ≤ 125 kg. * Documented CHC genotype 1 with HCV RNA ≥10,000 International Units (IU)/mL * Has IL-28B CC allele gene * Has had a liver biopsy without evidence of cirrhosis and hepatocellular carcinoma (non-invasive fibroscan and Fibrotest can also be used for staging of liver disease).
Exclusion criteria
* Co-infection with the human immunodeficiency virus (HIV) or hepatitis B virus (Hepatitis B surface antigen \[HBsAg\] or HIV positive). * Previously treated with an interferon and ribavirin regimen or HCV direct acting antiviral regimen. * Treatment for hepatitis C with any investigational medication, or prior treatments with herbal remedies with known hepatotoxicity * Receiving any medication(s) within 2 weeks prior to the Day 1 visit that are highly dependent on Cytochrome P450 3A4 (CYP3A4/5) for clearance, and for which elevated plasma concentrations could be associated with serious and/or life-threatening events * Participation in any other clinical trial within 30 days of the screening visit in this trial or intention to participate in another clinical trial during participation in this trial. * Evidence of decompensated liver disease or hepatocellular carcinoma (HCC) * Is diabetic and/or hypertensive with significant retinopathy * 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. * Evidence of active or suspected malignancy, or a history of malignancy, within the last 5 years * Hemoglobin \<12 g/dL for females and \<13 g/dL for males * Neutrophils \<1,500/mm\^3, or \<1,200/mm\^3 for participants of African descent * Platelets \<150,000/mm\^3 * Direct bilirubin \>1.5 x upper limit of normal (ULN) of the laboratory reference range.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) 24 Weeks After Completing Study Treatment (SVR24) | Up to Week 74 | SVR24 rates were determined for all participants in Arm 1 and Arm 2. HCV RNA viral load was determined using the Roche COBAS® AmpliPrep/COBAS® TaqMan HCV Test v1.0, which has a lower limit of quantification of 43 IU/mL. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Had Undetectable HCV RNA at Week 4 Achieving SVR24 | Up to Week 48 | SVR24 rates were determined for only participants that had undetectable HCV RNA at Week 4 of treatment (Arm 1a and Arm 2a). HCV RNA viral load was determined using the Roche COBAS® AmpliPrep/COBAS® TaqMan HCV Test v1.0, which has a lower limit of quantification of 43 IU/mL. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm 1: Peg-IFN + RBV Participants received an initial 4 week lead-in of peg-IFN + RBV. Following HCV RNA analysis at Week 4, participants with undetectable HCV RNA received open label peg-IFN + RBV for an additional 18 weeks (total of 24 weeks of peg-IFN/RBV therapy) \[Arm 1a\]. Participants with detectable HCV RNA at Week 4 had BOC added to the peg-IFN + RBV regimen at Week 6 and then followed the Response Guided Therapy (RGT) regimen for BOC + peg-IFN + RBV \[Arm 1b\]. | 368 |
| Arm 2: BOC + Peg-IFN + RBV Participants received an initial 4-week lead-in of peg-IFN + RBV. Following HCV RNA analysis at Week 4, all participants had BOC added to the peg-IFN + RBV regimen at Week 6 regardless of HCV RNA levels. Participants who had undetectable HCV RNA at Week 4 continued on the BOC + peg-IFN + RBV regimen for an additional 20 weeks (total of 24 weeks of BOC + peg-IFN + RBV therapy) \[Arm 2a\]. Participants with detectable HCV RNA at Week 4 followed the RGT regimen for BOC + peg-IFN + RBV \[Arm 2b\]. | 369 |
| Total | 737 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 3 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Lost to Follow-up | 11 | 12 |
| Overall Study | Physician Decision | 4 | 1 |
| Overall Study | Protocol Violation | 0 | 2 |
| Overall Study | Withdrawal by Subject | 4 | 4 |
Baseline characteristics
| Characteristic | Arm 1: Peg-IFN + RBV | Arm 2: BOC + Peg-IFN + RBV | Total |
|---|---|---|---|
| Age, Continuous | 43.9 Years STANDARD_DEVIATION 12 | 42.4 Years STANDARD_DEVIATION 12.4 | 43.1 Years STANDARD_DEVIATION 12.2 |
| Sex: Female, Male Female | 167 Participants | 148 Participants | 315 Participants |
| Sex: Female, Male Male | 201 Participants | 221 Participants | 422 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 348 / 368 | 351 / 369 |
| serious Total, serious adverse events | 27 / 368 | 37 / 369 |
Outcome results
Primary
Percentage of Participants With Undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) 24 Weeks After Completing Study Treatment (SVR24)
SVR24 rates were determined for all participants in Arm 1 and Arm 2. HCV RNA viral load was determined using the Roche COBAS® AmpliPrep/COBAS® TaqMan HCV Test v1.0, which has a lower limit of quantification of 43 IU/mL.
Time frame: Up to Week 74
Population: The Full Analysis Set (FAS) consisted of all participants who completed the 4-week peg-IFN + RBV lead-in and who were randomized at Week 4.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: Peg-IFN + RBV | Percentage of Participants With Undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) 24 Weeks After Completing Study Treatment (SVR24) | 86.7 Percentage of participants |
| Arm 2: BOC + Peg-IFN + RBV | Percentage of Participants With Undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) 24 Weeks After Completing Study Treatment (SVR24) | 88.3 Percentage of participants |
Comparison: Difference in percentage of participants achieving SVR2495% CI: [-3.2, 6.5]
Secondary
Percentage of Participants Who Had Undetectable HCV RNA at Week 4 Achieving SVR24
SVR24 rates were determined for only participants that had undetectable HCV RNA at Week 4 of treatment (Arm 1a and Arm 2a). HCV RNA viral load was determined using the Roche COBAS® AmpliPrep/COBAS® TaqMan HCV Test v1.0, which has a lower limit of quantification of 43 IU/mL.
Time frame: Up to Week 48
Population: The Full Analysis Set (FAS) consisted of all participants who completed the 4-week peg-IFN + RBV lead-in, who were randomized at Week 4, and also had undetectable HCV RNA at Week 4.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: Peg-IFN + RBV | Percentage of Participants Who Had Undetectable HCV RNA at Week 4 Achieving SVR24 | 87.0 Percentage of participants |
| Arm 2: BOC + Peg-IFN + RBV | Percentage of Participants Who Had Undetectable HCV RNA at Week 4 Achieving SVR24 | 97.2 Percentage of participants |
95% CI: [2.5, 18.1]