Hepatitis C
Conditions
Brief summary
This study is being done to find out if the addition of boceprevir to standard of care (SOC) treatment with peginterferon alfa-2b (PegIFN-2b) + ribavirin (RBV) is effective for participants with chronic hepatitis C (CHC) genotype 1 and cirrhosis who were not successfully treated by previous SOC. All participants will receive treatment with SOC alone for 4 weeks and then boceprevir will be added to the treatment regimen for 44 additional weeks of combined treatment.
Interventions
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Weight between 40 kg and 125 kg * Documented CHC genotype 1 infection * Previous course of treatment with SOC (PegIFN-2a or PegIFN-2b + RBV) with a documented non-response * Documented diagnosis of cirrhosis * No evidence of hepatocellular carcinoma (HCC) by ultrasound * Participant and partner of participant must agree to use 2 effective contraceptives as specified for at least 2 weeks prior to Day 1 of treatment and continue until at least 6 months after last dose of study drug (7 months for male participants)
Exclusion criteria
* Co-infection with human immunodeficiency virus (HIV) or hepatitis B virus * Use of any investigational drugs within 30 days prior to study enrollment * Participation in any other clinical trial within 30 days of study enrollment or intention to participate in another clinical trial during this study * Evidence of present or previous decompensated liver disease including, but not limited to, a history or presence of clinical ascites or hepatic encephalopathy. Only participants with large (F3) esophageal varices, as determined in an esophagogastroduodenoscopy (EGD) performed within the past 12 months according to international guidelines will be excluded. * Clinically significant ocular examination findings * Pre-existing significant psychiatric condition(s) * Clinical diagnosis of active or recent substance abuse * Evidence of active or suspected malignancy, or a history of malignancy, within the last 3 years (except adequately treated carcinoma in situ and basal cell carcinoma of the skin)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieve Sustained Virological Response at Follow-up Week 24 (SVR24) | Week 72 (24 weeks after end of treatment) | Hepatitis C Virus (HCV) ribonucleic acid (RNA) was measured using a polymerase chain reaction assay. SVR24 was defined as HCV RNA less than the Limit of Quantification (\<25 International Units (IU)/mL) 24 weeks after the end of the Treatment Period. |
| Percentage of Participants With One or More Adverse Events | Up to 48 weeks (Lead-in and Treatment Periods) | Adverse events were monitored during the Lead-in and Treatment Periods |
| Percentage of Participants With an Adverse Event Leading to Discontinuation of Study Medication | Up to 48 weeks (Lead-in and Treatment Periods) | Adverse events were monitored during the Lead-in and Treatment Periods |
Participant flow
Pre-assignment details
A total of 130 participants were screened. Sixty participants passed screening, but 2 of these participants were excluded before assignment because standard of care treatment was not received during the Lead-in Period.
Participants by arm
| Arm | Count |
|---|---|
| Overall Participants Participants received PegIFN-2b (once weekly, 1.5 µg/kg subcutaneously) + RBV (capsules, orally, weight-based dose from 800-1400 mg/day divided into two daily doses) for 4 weeks during the Lead-in Period and then 44 additional weeks of treatment in the Treatment Period receiving PegIFN-2b (once weekly, 1.5 µg/kg subcutaneously) + RBV (capsules, orally, weight-based dose from 800-1400 mg/day divided into two daily doses) + boceprevir (capsules, orally, 800 mg three times per day). After completion of treatment, follow-up continued for an additional 24 weeks. | 58 |
| Total | 58 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Treatment / Follow-up: Week 4 to Week 72 | Adverse Event | 5 |
| Treatment / Follow-up: Week 4 to Week 72 | Lack of Efficacy | 20 |
| Treatment / Follow-up: Week 4 to Week 72 | No boceprevir during Treatment Period | 4 |
| Treatment / Follow-up: Week 4 to Week 72 | No information available | 2 |
| Treatment / Follow-up: Week 4 to Week 72 | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Overall Participants |
|---|---|
| Age, Continuous | 59.3 Years STANDARD_DEVIATION 9.2 |
| Sex: Female, Male Female | 19 Participants |
| Sex: Female, Male Male | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 56 / 58 |
| serious Total, serious adverse events | 10 / 58 |
Outcome results
Primary
Percentage of Participants Who Achieve Sustained Virological Response at Follow-up Week 24 (SVR24)
Hepatitis C Virus (HCV) ribonucleic acid (RNA) was measured using a polymerase chain reaction assay. SVR24 was defined as HCV RNA less than the Limit of Quantification (\<25 International Units (IU)/mL) 24 weeks after the end of the Treatment Period.
Time frame: Week 72 (24 weeks after end of treatment)
Population: The Intent to Treat population included all participants who received at least 1 administration of boceprevir during the Treatment Period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Overall Participants | Percentage of Participants Who Achieve Sustained Virological Response at Follow-up Week 24 (SVR24) | 35.2 Percentage of participants |
Primary
Percentage of Participants With an Adverse Event Leading to Discontinuation of Study Medication
Adverse events were monitored during the Lead-in and Treatment Periods
Time frame: Up to 48 weeks (Lead-in and Treatment Periods)
Population: Safety Analysis Set 2 included all participants who received boceprevir during the Treatment Period
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Overall Participants | Percentage of Participants With an Adverse Event Leading to Discontinuation of Study Medication | 9.3 Percentage of participants |
Primary
Percentage of Participants With One or More Adverse Events
Adverse events were monitored during the Lead-in and Treatment Periods
Time frame: Up to 48 weeks (Lead-in and Treatment Periods)
Population: Safety Analysis Set 2 included all participants who received boceprevir during the Treatment Period
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Overall Participants | Percentage of Participants With One or More Adverse Events | 98.1 Percentage of participants |