Fibrosis, Hepatitis, Hepatitis C, Chronic, Liver Cirrhosis
Conditions
Brief summary
The objective of this study is to determine the effectiveness of PEG-Intron 1.5 ug/kg/wk plus REBETOL (ribavirin) 800-1400 mg/day in adults with chronic hepatitis C with moderate to severe liver fibrosis or cirrhosis who failed to respond to previous treatment with an alpha interferon in combination with ribavirin. Patients who do not respond to PEG-Intron plus REBETOL (ribavirin) will be enrolled in a long-term maintenance study to evaluate the effectiveness of PEG-Intron monotherapy versus no treatment for the prevention of disease progression (Protocols P02569 and P02570).
Interventions
PegIntron (peginterferon alfa-2b) administered at a dose of 1.5 mcg/kg subcutaneously (SC) once a week (QW) for up to 48 weeks
REBETOL (ribavirin) administered on a weight basis: 800-1400 mg/day orally (PO) for up to 48 weeks
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
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 * Positive for Hepatitis C * Nonresponder to previous treatment (minimum of 3 months) with an alpha Interferon plus ribavirin * Liver biopsy demonstrating moderate to severe fibrosis or cirrhosis
Exclusion criteria
* Any cause for the liver disease other than chronic hepatitis C * History or presence of complications of cirrhosis * Alcohol or illicit drug use or methadone treatment within the past 2 years * Treatment for chronic hepatitis C within the previous 6 months * Diseases or conditions that could interfere with the subject's participation in and completion of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sustained Virologic Response (SVR) Rate | Assessed at end of 24 weeks posttreatment follow-up | Number of participants with undetectable hepatitis C virus RNA (HCV-RNA) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sustained Virologic Response (SVR) for Participants With Undetectable HCV-RNA at Treatment Week 12 | 24 weeks posttreatment | Number of participants with undetectable HCV-RNA at Treatment Week 12 who had subsequent undetectable HCV-RNA after 24 weeks of posttreatment follow-up |
| Sustained Virologic Response (SVR) for Participants With Detectable But ≥2 Log Drop in HCV-RNA at Treatment Week 12 | 24 weeks posttreatment | Number of participants with detectable HCV-RNA but ≥2 log drop from baseline in HCV-RNA at Treatment Week 12 who had subsequent undetectable HCV-RNA after 24 weeks of posttreatment follow-up |
Participant flow
Pre-assignment details
Enrolled 2333; 21 subjects excluded due to Good Clinical Practice (GCP) non-compliance.
Participants by arm
| Arm | Count |
|---|---|
| PegIntron Plus Rebetol | 2,312 |
| Total | 2,312 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Administrative | 1 |
| Overall Study | Adverse Event | 165 |
| Overall Study | Did not meet eligibility criteria | 11 |
| Overall Study | Discontinued at Week 12 per protocol | 1,061 |
| Overall Study | Lost to Follow-up | 18 |
| Overall Study | Never entered follow-up | 7 |
| Overall Study | Protocol Violation | 24 |
| Overall Study | Withdrawal by Subject | 97 |
Baseline characteristics
| Characteristic | PegIntron Plus Rebetol |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 45 Participants |
| Age, Categorical Between 18 and 65 years | 2267 Participants |
| Age, Continuous | 49.2 years STANDARD_DEVIATION 8.1 |
| Hepatitis C Virus (HCV) Genotype Genotype 1 | 1859 number of participants |
| Hepatitis C Virus (HCV) Genotype Genotype 2 | 75 number of participants |
| Hepatitis C Virus (HCV) Genotype Genotype 3 | 293 number of participants |
| Hepatitis C Virus (HCV) Genotype Genotype 4 | 68 number of participants |
| Hepatitis C Virus (HCV) Genotype Missing | 9 number of participants |
| Hepatitis C Virus (HCV) Genotype Nontypable | 8 number of participants |
| METAVIR Fibrosis score F1 | 2 number of participants |
| METAVIR Fibrosis score F2 | 658 number of participants |
| METAVIR Fibrosis score F3 | 676 number of participants |
| METAVIR Fibrosis score F4 | 974 number of participants |
| METAVIR Fibrosis score Missing | 2 number of participants |
| Sex: Female, Male Female | 662 Participants |
| Sex: Female, Male Male | 1650 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2,201 / 2,312 |
| serious Total, serious adverse events | 200 / 2,312 |
Outcome results
Primary
Sustained Virologic Response (SVR) Rate
Number of participants with undetectable hepatitis C virus RNA (HCV-RNA)
Time frame: Assessed at end of 24 weeks posttreatment follow-up
Population: Participants who received at least one dose of study medication
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PegIntron Plus Rebetol | Sustained Virologic Response (SVR) Rate | 497 Participants |
99% CI: [0.195, 0.239]
Secondary
Sustained Virologic Response (SVR) for Participants With Detectable But ≥2 Log Drop in HCV-RNA at Treatment Week 12
Number of participants with detectable HCV-RNA but ≥2 log drop from baseline in HCV-RNA at Treatment Week 12 who had subsequent undetectable HCV-RNA after 24 weeks of posttreatment follow-up
Time frame: 24 weeks posttreatment
Population: Participants with detectable but \>=2 log drop in HCV-RNA at Treatment Week 12
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PegIntron Plus Rebetol | Sustained Virologic Response (SVR) for Participants With Detectable But ≥2 Log Drop in HCV-RNA at Treatment Week 12 | 23 Participants |
95% CI: [0.076, 0.169]
Secondary
Sustained Virologic Response (SVR) for Participants With Undetectable HCV-RNA at Treatment Week 12
Number of participants with undetectable HCV-RNA at Treatment Week 12 who had subsequent undetectable HCV-RNA after 24 weeks of posttreatment follow-up
Time frame: 24 weeks posttreatment
Population: Participants who had undetectable HCV-RNA at Treatment Week 12
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PegIntron Plus Rebetol | Sustained Virologic Response (SVR) for Participants With Undetectable HCV-RNA at Treatment Week 12 | 463 Participants |
95% CI: [0.529, 0.596]