Hepatitis C, Chronic
Conditions
Brief summary
This is an open-label, randomized, comparative, multicenter, 48-week study designed to evaluate the efficacy and safety of combination treatment with pegylated interferon and ribavirin in adult subjects with a diagnosis of compensated chronic hepatitis C (hepatitis C virus (HCV)-ribonucleic acid (RNA) positive) (Genotype 1). All subjects will complete 24 weeks of treatment, termed the Pilot Treatment Program, after which all eligible subjects will be randomly assigned to one of two study groups. One group will be followed for an additional 48 weeks without study medication, while the other will be continuously treated for an additional 24 weeks and then followed for another 24 weeks without study medication. Sustained virologic response, defined as undetectable HCV-RNA in serum at the end of the follow-up period, will be measured along with other outcomes.
Detailed description
This is an open-label, randomized, comparative, multicenter study for evaluation of PegIntron/Ribavirin therapy in the efficacy and safety in adult subjects with a diagnosis of compensated chronic hepatitis C (HCV-RNA+) (Genotype 1). This is a 48-week study, for which all subjects should participate in the Pilot Treatment Program and complete 24 weeks treatment. To avoid a treatment gap, subjects who will be screened and eligible subjects will sign informed consent prior to the end of the Pilot Treatment Program. After completion of the Pilot Treatment Program, all eligible subjects will be randomly assigned to either study group. Subjects in the 24-Week Treatment arm will be followed-up without study medication for 48 weeks; subjects in the 48-Week Treatment arm will be continuously treated for another 24 weeks and all subjects in the 48-Week Treatment arm will be followed for another 24 weeks after completion of the treatment period. Subjects in both arms will be evaluated at screening, randomization, 4, 8, 12, 16, 20, 24, 28, 36 and 48 weeks after randomization.
Interventions
Powder for injection in vial (120 microgram strength), subcutaneous, dose of 1.5 micrograms/kg weekly for 24 weeks during the pilot treatment program
DRUGRibavirin
200 mg capsules, oral, weight-based dose of 1000 or 1200 mg, daily for for 24 weeks during the pilot treatment program
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
* Subject must be willing to give written informed consent and be able to adhere to dose and visit schedules. * Males and non-pregnant females and aged \>= 18 years, subjects who are over 65 years of age must be in generally good health and must be discussed with and approved by the principal investigator prior to entry. * The laboratory evaluation within 6 months prior to entering the Pilot Treatment Program must meet the following criteria: * Hemoglobin values of \>= 12 g/dL for females and \>= 13 g/dL for males * Neutrophil count \>= 1.5 X10\^9/L * Platelets count \>= 100 x 10\^9/L * Total bilirubin \< 1.5 mg/dL * Serum creatinine within normal limits * Positive serum HCV-RNA (\>= 50 IU (100 copy numbers)/mL) * Anti-HCV positive * Available HCV genotype 1 * Liver biopsy performed within 12 months prior to entry to this protocol with a pathology report confirming that the histological diagnosis is consistent with chronic hepatitis (METAVIR system \>=F1). * Compensated liver disease with the following hematological, biochemical, and serologic criteria at the screening visit: * Hemoglobin values of \>= 9 g/dL * Neutrophil count \>= 0.75 x 10\^9/L * Platelets count \>= 50 x 10\^9/L * Prothrombin time (PT) prolong \<= 3 sec, International Normalized Ratio (INR) \<= 1.2 * Total bilirubin \<= 3 mg/dL * Within normal limits (subjects requiring medication to maintain TSH levels in the normal range are eligible if all other inclusion/
Exclusion criteria
are met). * Anti-Human Immunodeficiency Virus (HIV) negative. * Alpha-fetoprotein (AFP) value within normal limits obtained within 12 months prior to entry. Results above the upper limit of normal but \<= 50 ng/mL require both of the following: * AFP value \<= 50 ng/mL obtained within 9 months prior to entry in the study or during the Screening period, and Ultrasound obtained within 9 months prior to entry or in the screening period in the study for evidence of not having hepatocellular carcinoma. * A urine pregnancy test obtained prior to the initiation of pilot treatment must be negative. Female subjects must not be breast feeding. * Reconfirmation that sexually-active subjects are practicing acceptable methods of contraception during screening period. * Complete 24 weeks treatment of the Pilot Treatment Program with Peg-Intron + Ribavirin. * Must be never treated with interferon for HCV infected hepatitis (treatment naïve) before the Pilot Treatment Program. * The total amount of Peg-Intron and Ribavirin received during the pilot treatment program must achieve more than 80% of the recommended dosage.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Participants Who Achieved a Sustained Virologic Response (SVR) | 24 weeks of follow-up after either 24 or 48 weeks of anti-HCV therapy | Sustained virologic response was defined as hepatitis C virus ribonucleic acid \[HCV-RNA\] levels below assay detection 24 weeks after termination of anti-HCV therapy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Participants Who Achieved a Virologic Response 48 Weeks After Randomization. | 48 weeks after randomization (with 24 weeks of treatment immediately before randomization and either 0 or 24 weeks of treatment immediately after randomization) | Virologic response was defined as undetectable HCV-RNA level in the blood. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 24-Week Treatment Genotype 1 hepatitis C virus \[HCV\] subjects treated for a total of 24 weeks, during the pilot treatment program (immediately before randomization) | 78 |
| 48-Week Treatment Genotype 1 HCV subjects treated for a total of 48 weeks: 24 weeks during the pilot treatment program (immediately before randomization) plus 24 weeks during the extended treatment program (immediately after randomization) | 82 |
| Total | 160 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 5 |
| Overall Study | Lost to Follow-up | 3 | 2 |
| Overall Study | Physician Decision | 12 | 0 |
| Overall Study | Protocol Violation | 2 | 1 |
| Overall Study | Withdrawal by Subject | 6 | 2 |
Baseline characteristics
| Characteristic | 24-Week Treatment | 48-Week Treatment | Total |
|---|---|---|---|
| Age, Continuous | 50.63 years STANDARD_DEVIATION 10.6 | 50.46 years STANDARD_DEVIATION 10.93 | 50.55 years STANDARD_DEVIATION 10.74 |
| Region of Enrollment Taiwan, Province Of China | 78 participants | 82 participants | 160 participants |
| Sex: Female, Male Female | 20 Participants | 39 Participants | 59 Participants |
| Sex: Female, Male Male | 58 Participants | 43 Participants | 101 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 29 / 78 | 47 / 82 |
| serious Total, serious adverse events | 5 / 78 | 8 / 82 |
Outcome results
Primary
The Percentage of Participants Who Achieved a Sustained Virologic Response (SVR)
Sustained virologic response was defined as hepatitis C virus ribonucleic acid \[HCV-RNA\] levels below assay detection 24 weeks after termination of anti-HCV therapy
Time frame: 24 weeks of follow-up after either 24 or 48 weeks of anti-HCV therapy
Population: Intention to treat \[ITT\] population defined as participants who received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 24-Week Treatment | The Percentage of Participants Who Achieved a Sustained Virologic Response (SVR) | 56.41 Percentage of participants |
| 48-Week Treatment | The Percentage of Participants Who Achieved a Sustained Virologic Response (SVR) | 67.07 Percentage of participants |
p-value: 0.1651Chi-squared
Secondary
The Percentage of Participants Who Achieved a Virologic Response 48 Weeks After Randomization.
Virologic response was defined as undetectable HCV-RNA level in the blood.
Time frame: 48 weeks after randomization (with 24 weeks of treatment immediately before randomization and either 0 or 24 weeks of treatment immediately after randomization)
Population: Intention to treat \[ITT\] population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 24-Week Treatment | The Percentage of Participants Who Achieved a Virologic Response 48 Weeks After Randomization. | 57.69 Percentage of Participants |
| 48-Week Treatment | The Percentage of Participants Who Achieved a Virologic Response 48 Weeks After Randomization. | 67.07 Percentage of Participants |