Hepatitis C, Chronic, Liver Cirrhosis
Conditions
Keywords
hepatitis C
Brief summary
The objective is to evaluate the efficacy and safety of combination therapy with peginterferon alfa-2b 1.0 µg/kg/week subcutaneous (SC) + ribavirin administered for 48 weeks in participants with chronic hepatitis C and type C compensated liver cirrhosis. Participants who are hepatitis C virus ribonucleic acid (HCV-RNA) positive after 24 weeks of treatment will be discontinued from therapy.
Interventions
BIOLOGICALPeginterferon alfa-2b
Administered at 1.0 µg/kg/week SC for 48 weeks
DRUGRibavirin
Administered based on body weight and hemoglobin value at Screening: 600-1000 mg/day for subjects with hemoglobin value at screening \>=14g/dL, and 400-800 mg/day for subjects with hemoglobin value at screening \>=12g/dL and \<14g/dL; treatment duration is 48 weeks
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Adults aged 20-70 years. * Positive quantitative serum HCV-RNA. * Participants classified as A in Child-Pugh classification, and who do not have ascites or hepatic encephalopathy. * Diagnosed with type C compensated liver cirrhosis based on liver biopsy performed within 3 years or latest celioscopy. * Prolonged prothrombin time by \<=3.0 sec. * Participants and partners of participants willing to use adequate contraception during the course of the study. * Participants who can be hospitalized for at least 14 days since treatment initiation. * Weight \>40 kg and \<=100 kg * Hematology laboratory results of: * hemoglobin \>=12 g/dL * neutrophil count \>=1,500/mm\^3 * platelet count \>=70,000/ mm\^3 * Blood chemistry results of: * albumin and direct bilirubin within normal limits * alpha fetoprotein (AFP) within reference range * AFP-L3\<=10% * Protein induced by vitamin K (PIVKA)-II \<=100 mAU/mL
Exclusion criteria
* Participants who did not previously respond virologically to combination therapy with interferon (including polyethylene glycol-modified interferon) and ribavirin * Participants who had previously received treatment with interferon for whom at least 90 days have not elapsed since the end of previous treatment * Participants who have received treatment within 14 days prior to registration with injectable preparations containing glycyrrhizin/cysteine/glycyron or shosaikoto * Participants who have received administration of drugs having antiviral, anti-tumor, or immuno-modulating effect (including glucocorticoids and radiation therapy) within 90 days prior to registration (excluding local administration and topicals) * Participants who have received other investigational drugs within 180 days prior to registration * Hepatitis B surface (HBs) antigen positive * Antinuclear antibody \>=320 times * Serum creatinine exceeding the upper limit of reference range * Participants with fasting blood glucose \>=110 mg/dL (participants with fasting blood glucose \>=110 mg/dL and \<126 mg/dL can be registered if their hemoglobin A1C (HbA1c) is \<6.5%) \[fasting blood glucose should be measured when participants are not receiving treatment for diabetes mellitus\] * Participants with any of the following: diabetes mellitus that requires treatment; thyroid function disorder not controlled by treatment; liver disease such as autoimmune, alcoholic and drug-induced liver diseases; hemophilia; arrhythmia requiring treatment; co-existing hypertension not controlled by drug therapy (systolic blood pressure \[BP\] \>=160mmHg or diastolic BP\>=100mmHg); chronic pulmonary disease; hemoglobinopathies (thalassemia, sickle cell anemia); malignant tumors or who have a history of malignant tumor within the past 5 years; organ transplants (other than cornea and hair transplant) * Participants with or who have a history of primary biliary cirrhosis, liver failure, hepatic carcinoma; decompensated liver cirrhosis with any the following diseases: ascites, jaundice, variceal hemorrhage, esophageal or gastric varices requiring treatment, hepatic encephalopathy, and idiopathic bacterial peritonitis; depression or schizophrenia requiring treatment, or suicidal attempt or suicidal ideation; epileptic seizures requiring treatment; angina, cardiac failure, myocardial infarction, or life-threatening arrhythmia; autoimmune disease (Hashimoto's disease, Crohn's disease, ulcerative colitis, chronic rheumatoid arthritis, idiopathic thrombocytopenic purpura, systemic erythematosus, autoimmune hemolytic anemia, scleroderma, etc.); hepatic carcinoma * Participants with a history of hypersensitivity to interferon preparations, biological products such as vaccine, or nucleoside analogs, and those with specific reaction to pegylated interferon alfa-2b in the prick test conducted before the initiation of treatment * Women who are pregnant or nursing as well as women for whom pregnancy cannot be ruled out by serum human chorionic gonadotropin (HCG) test conducted during the screening period. Male participants with partners who are pregnant.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Undetectable HCV-RNA at Week 72 (Sustained Virologic Response) | Measured at 24 weeks after 48 weeks treatment (72 weeks) | Serum HCV-RNA was qualitatively measured by reverse transcriptase polymerase chain reaction (RT-PCR) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Undetectable HCV-RNA at Week 24 | Week 24 | Serum HCV-RNA was qualitatively measured by reverse transcriptase polymerase chain reaction (RT-PCR) |
| Number of Participants With Undetectable HCV-RNA at End of Treatment | Up to 48 weeks | Serum HCV-RNA was qualitatively measured by reverse transcriptase polymerase chain reaction (RT-PCR) |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Peginterferon Alfa-2b + Ribavirin Peginterferon alfa-2b administered at 1.0 µg/kg/week SC for 48 weeks plus ribavirin administered based on body weight and hemoglobin value at screening: 600-1000 mg/day
for subjects with hemoglobin value at screening \>=14g/dL, and 400-800 mg/day for subjects with hemoglobin value at screening \>=12g/dL and \<14g/dL for 48 weeks | 102 |
| Total | 102 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 8 |
| Overall Study | Discontinuance criteria met | 7 |
| Overall Study | HCV-RNA positive conversion | 34 |
| Overall Study | Lack of Efficacy | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Peginterferon Alfa-2b + Ribavirin |
|---|---|
| Age, Continuous | 58.6 Years STANDARD_DEVIATION 8.1 |
| Region of Enrollment Japan | 102 Participants |
| Sex: Female, Male Female | 48 Participants |
| Sex: Female, Male Male | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 102 / 102 |
| serious Total, serious adverse events | 14 / 102 |
Outcome results
Primary
Number of Participants With Undetectable HCV-RNA at Week 72 (Sustained Virologic Response)
Serum HCV-RNA was qualitatively measured by reverse transcriptase polymerase chain reaction (RT-PCR)
Time frame: Measured at 24 weeks after 48 weeks treatment (72 weeks)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Peginterferon Alfa-2b + Ribavirin | Number of Participants With Undetectable HCV-RNA at Week 72 (Sustained Virologic Response) | Undetectable HCV-RNA | 41 Participants |
| Peginterferon Alfa-2b + Ribavirin | Number of Participants With Undetectable HCV-RNA at Week 72 (Sustained Virologic Response) | Detectable HCV-RNA | 40 Participants |
| Peginterferon Alfa-2b + Ribavirin | Number of Participants With Undetectable HCV-RNA at Week 72 (Sustained Virologic Response) | Unknown (data not available) | 21 Participants |
Secondary
Number of Participants With Undetectable HCV-RNA at End of Treatment
Serum HCV-RNA was qualitatively measured by reverse transcriptase polymerase chain reaction (RT-PCR)
Time frame: Up to 48 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Peginterferon Alfa-2b + Ribavirin | Number of Participants With Undetectable HCV-RNA at End of Treatment | Undetectable HCV-RNA | 59 Participants |
| Peginterferon Alfa-2b + Ribavirin | Number of Participants With Undetectable HCV-RNA at End of Treatment | Detectable HCV-RNA | 43 Participants |
| Peginterferon Alfa-2b + Ribavirin | Number of Participants With Undetectable HCV-RNA at End of Treatment | Unknown (data not available) | 0 Participants |
Secondary
Number of Participants With Undetectable HCV-RNA at Week 24
Serum HCV-RNA was qualitatively measured by reverse transcriptase polymerase chain reaction (RT-PCR)
Time frame: Week 24
Population: Peginterferon alfa-2b administered at 1.0 μg/kg/week SC for 48 weeks plus ribavirin administered based on body weight and hemoglobin value at screening: 600-1000 mg/day for subjects with hemoglobin value at screening \>=14g/dL, and 400-800 mg/day for subjects with hemoglobin value at screening \>=12g/dL and \<14g/dL for 48 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Peginterferon Alfa-2b + Ribavirin | Number of Participants With Undetectable HCV-RNA at Week 24 | Undetectable HCV-RNA | 61 Participants |
| Peginterferon Alfa-2b + Ribavirin | Number of Participants With Undetectable HCV-RNA at Week 24 | Detectable HCV-RNA | 35 Participants |
| Peginterferon Alfa-2b + Ribavirin | Number of Participants With Undetectable HCV-RNA at Week 24 | Unknown (data not available) | 6 Participants |