Hepatitis C, Hepatitis C, Chronic
Conditions
Brief summary
The objective of this study is to determine the relapse rate in the French patient population with chronic hepatitis C (CHC) previously treated with PegInterferon Alfa-2b (Peg-IFN alfa-2b) plus Ribavirin according to standard clinical practice. Treatment was to be completed prior to the enrollment in the current study. The study will also aim to identify factors that are predictive of relapse. Relapse rate is defined as the percentage of patients with negative viral load at end of treatment who again have positive viral load at 6 months after the end of treatment.
Detailed description
Non-probability sampling: The study population consists of adult patients over the age of 18 affected by CHC who were previously treated for the first time with Peg-IFN alfa-2b plus ribavirin and achieved end-of-treatment response. Five hundred ninety patients must be recruited in order to evaluate the objectives of the study. The patients must meet all inclusion criteria and not meet any of the exclusion criteria in order to be included in the study.
Interventions
BIOLOGICALPeg-IFN alfa-2b
Peg-IFN alfa-2b administered in accordance with approved labeling
DRUGRibavirin
Ribavirin administered in accordance with approved labeling
Sponsors
Merck Sharp & Dohme LLC
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* The patient must demonstrate his/her continued willingness to participate in the study. * The patient must be at least 18 years of age, of either gender. * Patients with chronic hepatitis C (any genotype) who received Peg-IFN alfa-2b + Ribavirin as first treatment for hepatitis C. * Negative HCV-RNA at the end of treatment (24 or 48 weeks according to the product labeling as appropriate), measured by the assay used at each institution. Only institutions using an assay with a limit of detection of 50 IU/mL or less will be eligible.
Exclusion criteria
* Patients who completed treatment with PegInterferon Alfa-2b plus Ribavirin more than 4 weeks before study entry. * Patients with positive HCV-RNA at the end of treatment (24 or 48 weeks according to the product labeling as appropriate). * Patients treated for a period shorter than the enrollment period. * Patients co-infected with human immunodeficiency virus (HIV). * Patients co-infected with hepatitis B virus (HBV). * Patients who do not use appropriate effective method of birth control after the end of treatment (according to legal recommendations).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Positive Hepatitis C Virus (HCV)-Ribonucleic Acid (RNA) at 24 Weeks Off-treatment | 24 weeks post end of treatment (EOT) | HCV-RNA virus levels were measured by polymerase chain reaction (PCR) assay 24 weeks post end of treatment (EOT) with Peg-IFN alfa-2b + ribavirin. Participants with positive HCV-RNA were considered relapsers. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Rapid Virologic Response (RVR), Early Virologic Response (EVR), or Slow Response Who Relapsed After Treatment | 24 weeks post EOT | Negative HCV-RNA at Week 4 of treatment with Peg-IFN alfa-2b + ribavirin was considered RVR; negative HCV-RNA at Week 12 of treatment with Peg-IFN alfa-2b + ribavirin was considered EVR; negative HCV-RNA between Week 12 and the end of treatment with Peg-IFN alfa-2b + ribavirin was considered a slow response. For participants who achieved RVR, EVR, or slow response, the relapse rate at 24 Weeks post EOT was to be determined on this observational study; relapse was defined as positive HCV-RNA. |
| Assessment of Pre-treatment Risk Factors of Relapse in Participants With Sustained Virologic Response | Baseline and 24 weeks post EOT | Baseline risk factors included but were not limited to viral load, genotype 1a versus 1b, histology, treatment compliance, gender, age, and substance abuse. Sustained virologic response was defined as having negative HCV-RNA at 24 weeks post EOT. Relapse was defined as positive HCV-RNA. |
| Number of Participants With Positive HCV-RNA at 72 Weeks Off-treatment | 72 weeks post EOT | HCV-RNA virus levels were measured by polymerase chain reaction (PCR) assay 72 weeks post EOT with Peg-IFN alfa-2b + ribavirin. Participants with positive HCV-RNA at Week 72 post EOT were considered late relapsers. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Peg-IFN Alfa-2b + Ribavirin Participants with chronic hepatitis C (CHC) treated with Peg-IFN alfa-2b + ribavirin as first treatment, in common clinical practice, who had negative hepatitis-C virus (HCV)-ribonucleic acid (RNA) by the end of treatment (24 or 48 weeks per product labeling). | 90 |
| Total | 90 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Consent date prior to study start date | 5 |
| Overall Study | Death | 1 |
| Overall Study | Inclusion criterion not met | 1 |
| Overall Study | Lost to Follow-up | 19 |
| Overall Study | No Visit 1 data | 1 |
| Overall Study | Positive HCV-RNA at Visit 2 | 13 |
Baseline characteristics
| Characteristic | Peg-IFN Alfa-2b + Ribavirin |
|---|---|
| Age, Continuous | 46.0 years STANDARD_DEVIATION 12.5 |
| Sex: Female, Male Female | 25 Participants |
| Sex: Female, Male Male | 65 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 21 / 96 |
| serious Total, serious adverse events | 5 / 96 |
Outcome results
Primary
Number of Participants With Positive Hepatitis C Virus (HCV)-Ribonucleic Acid (RNA) at 24 Weeks Off-treatment
HCV-RNA virus levels were measured by polymerase chain reaction (PCR) assay 24 weeks post end of treatment (EOT) with Peg-IFN alfa-2b + ribavirin. Participants with positive HCV-RNA were considered relapsers.
Time frame: 24 weeks post end of treatment (EOT)
Population: Of the 97 participants who started the study, 7 were excluded from analysis because of protocol violations. 90 participants underwent HCV-RNA testing at Week 24 post EOT.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Peg-IFN Alfa-2b + Ribavirin | Number of Participants With Positive Hepatitis C Virus (HCV)-Ribonucleic Acid (RNA) at 24 Weeks Off-treatment | 13 participants |
Secondary
Assessment of Pre-treatment Risk Factors of Relapse in Participants With Sustained Virologic Response
Baseline risk factors included but were not limited to viral load, genotype 1a versus 1b, histology, treatment compliance, gender, age, and substance abuse. Sustained virologic response was defined as having negative HCV-RNA at 24 weeks post EOT. Relapse was defined as positive HCV-RNA.
Time frame: Baseline and 24 weeks post EOT
Population: The planned analysis for this outcome measure was not performed due to insufficient enrollment.
Secondary
Number of Participants With Positive HCV-RNA at 72 Weeks Off-treatment
HCV-RNA virus levels were measured by polymerase chain reaction (PCR) assay 72 weeks post EOT with Peg-IFN alfa-2b + ribavirin. Participants with positive HCV-RNA at Week 72 post EOT were considered late relapsers.
Time frame: 72 weeks post EOT
Population: 77 of 90 participants had a negative HCV-RNA at Week 24 post EOT. These 77 were then evaluated for relapse at Week 72 post EOT.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Peg-IFN Alfa-2b + Ribavirin | Number of Participants With Positive HCV-RNA at 72 Weeks Off-treatment | 3 participants |
Secondary
Number of Participants With Rapid Virologic Response (RVR), Early Virologic Response (EVR), or Slow Response Who Relapsed After Treatment
Negative HCV-RNA at Week 4 of treatment with Peg-IFN alfa-2b + ribavirin was considered RVR; negative HCV-RNA at Week 12 of treatment with Peg-IFN alfa-2b + ribavirin was considered EVR; negative HCV-RNA between Week 12 and the end of treatment with Peg-IFN alfa-2b + ribavirin was considered a slow response. For participants who achieved RVR, EVR, or slow response, the relapse rate at 24 Weeks post EOT was to be determined on this observational study; relapse was defined as positive HCV-RNA.
Time frame: 24 weeks post EOT
Population: The planned analysis for this outcome measure was not performed due to insufficient enrollment.