Hepatitis C, Chronic
Conditions
Brief summary
This is a Phase IIIB randomized, controlled, multi-centre, open-label study of 24 versus 48 weeks therapy with Pegetron® (peginterferon alfa-2b + ribavirin) at standard doses in naïve Hepatitis C Virus (HCV) genotype 1 high viral load (HVL) participants who are Hepatitis C Virus-Ribonucleic Acid (HCV-RNA) negative at Week 4. HVL will be defined as HCV-RNA of \>600,000 IU/mL prior to the initiation of therapy. Participants with genotype 1 baseline HVL prescribed Pegetron® (peginterferon and ribavirin) in the usual manner in accordance with the marketing authorization and who are viral negative at Week 4 will be randomized at Week 8 to receive a total of 24 or 48 weeks of therapy. Participants will be required to have their baseline and Week-12 viral load analyzed by the same local laboratory using the standard of care test used by the site. Qualitative testing at Week 4, 8, 16-20, 24, and 48 may be conducted either by local laboratory or a central laboratory identified by the sponsor using an assay specified by the sponsor. No additional interventions outside of the clinic's standard of care and the conditions of the Canadian product monograph for Pegetron® will be applied to participants.
Interventions
DRUGCombination of pegylated interferon alfa-2b (PEG) and ribavirin (RBV)
1. Powder for Solution in Redipen® (pegylated interferon alfa-2b) (80, 100, 120, and 150 microgram strengths), subcutaneous, dose of 1.5 micrograms/kg, weekly for up to 24 or 48 weeks 2. 200 mg ribavirin capsules, oral, weight-based dose of 800, 1000, or 1200 mg, daily for up to 24 or 48 weeks
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 65 Years
Healthy volunteers
No
Inclusion criteria
* Must demonstrate willingness to participate in the study. * Diagnosed with chronic HCV. * Between 18 and 65 years of age of either gender and of any race. * a. HCV positive, \>600,000 IU/mL at baseline AND b. Genotype 1. * Suitable for treatment with Pegetron® per the Canadian product monograph. * Investigator has already decided to treat with PEGETRON REDIPEN® 1.5mcg/kg/week of peginterferon alpha-2b plus 800-1200 mg /day of ribavirin. * HCV-RNA negative at treatment week 4. * Meet certain minimum laboratory values at the week 4 screening visit. * Women of childbearing potential and male partners must agree to use a medically accepted method of contraception prior to screening, while receiving protocol-specified medication, and for 6 months after stopping the medication. Acceptable methods of contraception include condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide, medically prescribed IUD, oral or injectable hormonal contraceptive, and surgical sterilization (e.g. hysterectomy or tubal ligation).
Exclusion criteria
* Had previous interferon-based therapy for Chronic Hepatitis C. * Active Hepatitis B virus (HBV) infection. * Human Immunodeficiency Virus (HIV) antibody positive. * Cirrhotic (Stage 4 on Metavir system). * Uncontrolled history or current severe depression or psychoses. * Uncontrolled epilepsy. * Use of illicit drugs. * History of non-compliance to medical regimens. * Liver disease other than from chronic hepatitis C. * Participating in any other clinical study. * Used any investigational drugs within 30 days of screening. * Participants weighing \< 40 kg or \> 125 kg. * Pregnant women or women who plan to become pregnant or sexual partners of women who want to become pregnant.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Sustained Virologic Response | 24 weeks following completion of 24 or 48 weeks of therapy | Participants were tested for the presence of Hepatitis C Virus-Ribonucleic Acid (HCV-RNA) in blood by Qualitative Polymerase Chain Reaction (qPCR). If the HCV-RNA is not detectable, the participant is negative for HCV-RNA. Sustained virologic responders were participants negative for HCV-RNA at 24 weeks following the completion of therapy. A Participant that withdrew prior to 24 weeks following the completion of therapy was considered a non-responder. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Virological Relapse | 24 weeks following completion of 24 or 48 weeks of therapy | Participants were tested for the presence of Hepatitis C Virus-Ribonucleic Acid (HCV-RNA) in blood by Qualitative Polymerase Chain Reaction (qPCR). Virological relapse in participants was defined as having negative virology (HCV-RNA) at end of treatment, but positive virology (HCV-RNA) again at 24 weeks of follow up post treatment. |
Participant flow
Pre-assignment details
56 participants were enrolled. 51 participants were screening failures, were not randomized and are not included in the study. Of the 5 participants randomized, 2 did not meet inclusion/exclusion criteria. All 5 are included in the intent-to-treat (ITT) population.
Participants by arm
| Arm | Count |
|---|---|
| Pegetron® - 24 Weeks Participants are treated for 8 weeks and then randomized to an additional 16 weeks of treatment | 3 |
| Pegetron® - 48 Weeks Participants are treated for 8 weeks and then randomized to an additional 40 weeks of treatment | 2 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 0 | 1 |
Baseline characteristics
| Characteristic | Pegetron® - 24 Weeks | Pegetron® - 48 Weeks | Total |
|---|---|---|---|
| Age, Continuous | 54.0 years STANDARD_DEVIATION 9.5 | 22 years STANDARD_DEVIATION 0 | 41.2 years STANDARD_DEVIATION 18.8 |
| Region of Enrollment Canada | 3 participants | 2 participants | 5 participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 1 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 | 0 / 2 | 2 / 3 | 1 / 2 |
| serious Total, serious adverse events | 2 / 2 | 0 / 3 | 0 / 2 |
Outcome results
Primary
Number of Participants With a Sustained Virologic Response
Participants were tested for the presence of Hepatitis C Virus-Ribonucleic Acid (HCV-RNA) in blood by Qualitative Polymerase Chain Reaction (qPCR). If the HCV-RNA is not detectable, the participant is negative for HCV-RNA. Sustained virologic responders were participants negative for HCV-RNA at 24 weeks following the completion of therapy. A Participant that withdrew prior to 24 weeks following the completion of therapy was considered a non-responder.
Time frame: 24 weeks following completion of 24 or 48 weeks of therapy
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pegetron® - 24 Weeks | Number of Participants With a Sustained Virologic Response | Responders | 3 Participants |
| Pegetron® - 24 Weeks | Number of Participants With a Sustained Virologic Response | Non-responders | 0 Participants |
| Pegetron® - 48 Weeks | Number of Participants With a Sustained Virologic Response | Responders | 1 Participants |
| Pegetron® - 48 Weeks | Number of Participants With a Sustained Virologic Response | Non-responders | 1 Participants |
Secondary
Number of Participants With a Virological Relapse
Participants were tested for the presence of Hepatitis C Virus-Ribonucleic Acid (HCV-RNA) in blood by Qualitative Polymerase Chain Reaction (qPCR). Virological relapse in participants was defined as having negative virology (HCV-RNA) at end of treatment, but positive virology (HCV-RNA) again at 24 weeks of follow up post treatment.
Time frame: 24 weeks following completion of 24 or 48 weeks of therapy
Population: ITT population that completed the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pegetron® - 24 Weeks | Number of Participants With a Virological Relapse | Participants with Virological Relapse | 0 Participants |
| Pegetron® - 24 Weeks | Number of Participants With a Virological Relapse | Participants with No Virological Relapse | 3 Participants |
| Pegetron® - 48 Weeks | Number of Participants With a Virological Relapse | Participants with Virological Relapse | 0 Participants |
| Pegetron® - 48 Weeks | Number of Participants With a Virological Relapse | Participants with No Virological Relapse | 1 Participants |