Chronic Hepatitis C, Cirrhosis
Conditions
Keywords
Hepatitis C; Cirrhosis
Brief summary
The objective of the study is to evaluate the safety and efficacy of PEG-Intron vs. no treatment for the prevention of disease progression in adult subjects with compensated cirrhosis secondary to chronic hepatitis C, who failed to respond to therapy with an a interferon plus ribavirin.
Interventions
BIOLOGICALpeginterferon alfa-2b (SCH 54031)
0.5 µg/kg subcutaneously once weekly for 60 months
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
* Age at entry 18-65 years; * Non-responders to previous treatment (minimum of 3 months) with an alpha interferon plus ribavirin; * Liver biopsy demonstrating cirrhosis
Exclusion criteria
* Any other cause for liver disease other than chronic hepatitis C; * History or presence of complications of cirrhosis; * Alcohol or illicit drug abuse or treatment with methadone within the past 2 years; * Diseases or conditions that could interfere with participation in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Observation of the First Clinical Event Experienced by a Subject | Up to 60 months of treatment or observation, or when 98 subjects experience at least one clinical event | Clinical events are liver decompensation \[variceal bleeding, development of Child-Pugh Class C, hepatic encephalopathy ≥Grade 2, ascites\], hepatic carcinoma, death, and/or liver transplantation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Observation of the Disease Progression Experienced by a Subject | Up to 60 months of treatment or observation, or when 98 subjects experience at least one clinical event | Disease progression was observation of any clinical event defined for the primary outcome, plus any of development of Child-Pugh Class B, emergence of varices, or enlargement of pre-existing varices requiring additional therapy. |
Participant flow
Pre-assignment details
Analysis population is modified intent to treat (MITT), comprising 626 randomized subjects from sites compliant with GCP (Good Clinical Practice). Two sites were closed due to GCP noncompliance, and the 5 subjects from these sites were excluded from analyses.
Participants by arm
| Arm | Count |
|---|---|
| PegIntron PegIntron 0.5 µg/kg subcutaneously once weekly as maintenance therapy for 60 months with a 4-week post-treatment follow-up | 311 |
| Untreated Control | 315 |
| Total | 626 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative | 1 | 1 |
| Overall Study | Adverse Event | 53 | 12 |
| Overall Study | Did Not Meet Protocol Eligibility | 2 | 2 |
| Overall Study | Lost to Follow-up | 5 | 5 |
| Overall Study | Noncompliance With Protocol | 4 | 12 |
| Overall Study | Protocol-defined Clinical Event | 17 | 32 |
| Overall Study | Withdrawal by Subject | 34 | 54 |
Baseline characteristics
| Characteristic | PegIntron | Untreated Control | Total |
|---|---|---|---|
| Age, Customized <=50 years | 130 Participants | 132 Participants | 262 Participants |
| Age, Customized >50 years | 181 Participants | 183 Participants | 364 Participants |
| Sex: Female, Male Female | 105 Participants | 100 Participants | 205 Participants |
| Sex: Female, Male Male | 206 Participants | 215 Participants | 421 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 290 / 311 | 260 / 315 |
| serious Total, serious adverse events | 93 / 311 | 74 / 315 |
Outcome results
Primary
Time to Observation of the First Clinical Event Experienced by a Subject
Clinical events are liver decompensation \[variceal bleeding, development of Child-Pugh Class C, hepatic encephalopathy ≥Grade 2, ascites\], hepatic carcinoma, death, and/or liver transplantation
Time frame: Up to 60 months of treatment or observation, or when 98 subjects experience at least one clinical event
Population: Analysis population is modified intent to treat (MITT), comprising all randomized subjects from sites compliant with GCP (Good Clinical Practice). Two sites were closed due to GCP noncompliance, and the 5 subjects from these sites were excluded from efficacy analyses.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PegIntron | Time to Observation of the First Clinical Event Experienced by a Subject | >30 to 36 Months | 1 Participants |
| PegIntron | Time to Observation of the First Clinical Event Experienced by a Subject | >6 to 12 Months | 5 Participants |
| PegIntron | Time to Observation of the First Clinical Event Experienced by a Subject | >36 to 42 Months | 0 Participants |
| PegIntron | Time to Observation of the First Clinical Event Experienced by a Subject | >18 to 24 Months | 3 Participants |
| PegIntron | Time to Observation of the First Clinical Event Experienced by a Subject | >42 to 48 Months | 2 Participants |
| PegIntron | Time to Observation of the First Clinical Event Experienced by a Subject | <=6 Months | 3 Participants |
| PegIntron | Time to Observation of the First Clinical Event Experienced by a Subject | >48 to 54 Months | 2 Participants |
| PegIntron | Time to Observation of the First Clinical Event Experienced by a Subject | >24 to 30 Months | 7 Participants |
| PegIntron | Time to Observation of the First Clinical Event Experienced by a Subject | >54 to 60 Months | 0 Participants |
| PegIntron | Time to Observation of the First Clinical Event Experienced by a Subject | Total Over Study | 27 Participants |
| PegIntron | Time to Observation of the First Clinical Event Experienced by a Subject | >12 to 18 Months | 4 Participants |
| Untreated Control | Time to Observation of the First Clinical Event Experienced by a Subject | Total Over Study | 36 Participants |
| Untreated Control | Time to Observation of the First Clinical Event Experienced by a Subject | <=6 Months | 2 Participants |
| Untreated Control | Time to Observation of the First Clinical Event Experienced by a Subject | >6 to 12 Months | 5 Participants |
| Untreated Control | Time to Observation of the First Clinical Event Experienced by a Subject | >12 to 18 Months | 4 Participants |
| Untreated Control | Time to Observation of the First Clinical Event Experienced by a Subject | >18 to 24 Months | 7 Participants |
| Untreated Control | Time to Observation of the First Clinical Event Experienced by a Subject | >24 to 30 Months | 6 Participants |
| Untreated Control | Time to Observation of the First Clinical Event Experienced by a Subject | >30 to 36 Months | 6 Participants |
| Untreated Control | Time to Observation of the First Clinical Event Experienced by a Subject | >36 to 42 Months | 5 Participants |
| Untreated Control | Time to Observation of the First Clinical Event Experienced by a Subject | >42 to 48 Months | 0 Participants |
| Untreated Control | Time to Observation of the First Clinical Event Experienced by a Subject | >48 to 54 Months | 1 Participants |
| Untreated Control | Time to Observation of the First Clinical Event Experienced by a Subject | >54 to 60 Months | 0 Participants |
Comparison: The primary scientific hypothesis is that, 0.5 ug/kg subcutaneous once weekly PegIntron as maintenance therapy is efficacious, when compared to no treatment, in the prevention of clinical events in adult subjects with compensated cirrhosis (Metavir F4), secondary to Chronic Hepatitis C, who have failed to respond to therapy with any α interferon plus ribavirin.p-value: 0.143995% CI: [0.88, 2.396]Cox Proportional Hazards Model
Secondary
Time to Observation of the Disease Progression Experienced by a Subject
Disease progression was observation of any clinical event defined for the primary outcome, plus any of development of Child-Pugh Class B, emergence of varices, or enlargement of pre-existing varices requiring additional therapy.
Time frame: Up to 60 months of treatment or observation, or when 98 subjects experience at least one clinical event
Population: Analysis population is modified intent to treat (MITT), comprising all randomized subjects from sites compliant with GCP (Good Clinical Practice). Two sites were closed due to GCP noncompliance, and the 5 subjects from these sites were excluded from efficacy analyses.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PegIntron | Time to Observation of the Disease Progression Experienced by a Subject | >30 to 36 Months | 4 Participants |
| PegIntron | Time to Observation of the Disease Progression Experienced by a Subject | >36 to 42 Months | 2 Participants |
| PegIntron | Time to Observation of the Disease Progression Experienced by a Subject | >42 to 48 Months | 2 Participants |
| PegIntron | Time to Observation of the Disease Progression Experienced by a Subject | >54 to 60 Months | 1 Participants |
| PegIntron | Time to Observation of the Disease Progression Experienced by a Subject | Total Over Study | 63 Participants |
| PegIntron | Time to Observation of the Disease Progression Experienced by a Subject | <=6 Months | 16 Participants |
| PegIntron | Time to Observation of the Disease Progression Experienced by a Subject | >6 to 12 Months | 6 Participants |
| PegIntron | Time to Observation of the Disease Progression Experienced by a Subject | >12 to 18 Months | 5 Participants |
| PegIntron | Time to Observation of the Disease Progression Experienced by a Subject | >18 to 24 Months | 12 Participants |
| PegIntron | Time to Observation of the Disease Progression Experienced by a Subject | >24 to 30 Months | 10 Participants |
| PegIntron | Time to Observation of the Disease Progression Experienced by a Subject | >48 to 54 Months | 5 Participants |
| Untreated Control | Time to Observation of the Disease Progression Experienced by a Subject | >12 to 18 Months | 7 Participants |
| Untreated Control | Time to Observation of the Disease Progression Experienced by a Subject | >24 to 30 Months | 11 Participants |
| Untreated Control | Time to Observation of the Disease Progression Experienced by a Subject | >30 to 36 Months | 9 Participants |
| Untreated Control | Time to Observation of the Disease Progression Experienced by a Subject | <=6 Months | 17 Participants |
| Untreated Control | Time to Observation of the Disease Progression Experienced by a Subject | >36 to 42 Months | 4 Participants |
| Untreated Control | Time to Observation of the Disease Progression Experienced by a Subject | >48 to 54 Months | 4 Participants |
| Untreated Control | Time to Observation of the Disease Progression Experienced by a Subject | >42 to 48 Months | 6 Participants |
| Untreated Control | Time to Observation of the Disease Progression Experienced by a Subject | >6 to 12 Months | 6 Participants |
| Untreated Control | Time to Observation of the Disease Progression Experienced by a Subject | >54 to 60 Months | 3 Participants |
| Untreated Control | Time to Observation of the Disease Progression Experienced by a Subject | >18 to 24 Months | 20 Participants |
| Untreated Control | Time to Observation of the Disease Progression Experienced by a Subject | Total Over Study | 87 Participants |
Comparison: The secondary hypothesis is that 0.5 ug/kg subcutaneous once weekly PegIntron as maintenance therapy is efficacious, when compared to no treatment, in the prevention of disease progression in adult subjects with compensated cirrhosis (Metavir F4), secondary to Chronic Hepatitis C, who have failed to respond to therapy with any α interferon plus ribavirin.p-value: 0.00795% CI: [1.13, 2.166]Cox Proportional Hazards Model