Hepatitis C, Chronic
Conditions
Keywords
hepatitis C
Brief summary
The objective of this study is to compare the efficacy of peginterferon alfa-2b (PegIFN-2b) monotherapy administered at a dose of 0.5 ug/kg vs stronger neo minophagen C (SNMC) in participants with chronic hepatitis C (CHC) and liver fibrosis (Metavir fibrosis score of F2 and F3) who were previously treated with interferon. The trial will evaluate the effect of treatment on the progression of liver fibrosis, liver inflammation, and liver function. Treatment will be administered for up to 156 weeks with a 4-week follow-up.
Interventions
BIOLOGICALPeginterferon alfa-2b (PegIFN-2b)
PegIFN-2b administered at a dose of 0.5 ug/kg SC once a week for 156 weeks
DRUGComparator: Stronger neo minophagen C (SNMC)
SNMC (as glycyrrhizin-containing compound) administered at 40 mL by intravenous (IV) injection or IV infusion 3 times weekly for 156 weeks .
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with chronic hepatitis C previously treated with interferon * At least 20 years of age * Liver fibrosis score rated as F2 or F3 based on the result of liver biopsy at screening * Female patients willing to use contraception * Body weight from 35.0 kg to 110.0 kg (inclusive) * Positive for hepatitis C virus ribonucleic acid (HCV-RNA) by qualitative assay * Patients who meet the following laboratory criteria: * Serum alanine aminotransferase (ALT) level: \>60 IU/L * Neutrophil count: \>=1,200/mm\^3 * Platelet count: \>=100,000/mm\^3 * Serum potassium level: \>=3.5 mEq/L
Exclusion criteria
* Patients who received interferon therapy within 90 days of Screening * Patients who have received antiviral agents or antitumor agents, or immunomodulator therapy (including chronic glucocorticoids and radiotherapy) within 90 days of Screening (excluding local administration and topical use) * Patients who have received other investigational drugs within 90 days of Screening * Hepatitis B surface antigen (HBs)positive * Antinuclear antibody titer of 1:320 or higher * Creatinine level exceeding the upper limit of the reference range measured at screening test 2; * Fasting blood glucose level of \>=126 mg/dL * Patients on insulin therapy regardless of the fasting blood glucose level * Patients who have a concurrent or past history of any of the following conditions: liver cirrhosis, liver failure, or liver carcinoma; hepatic encephalopathy, esophageal varices requiring treatment, or ascites; suicidal attempt or ideation; epileptic seizures requiring drug therapy; angina pectoris, heart failure, myocardial infarction or fatal arrhythmia; autoimmune disease (Hashimoto's disease \[chronic thyroiditis\], Crohn's disease, ulcerative colitis, rheumatoid arthritis, idiopathic thrombocytopenic purpura, systemic lupus erythematosus, autoimmune hemolytic anemia, scleroderma, etc.); malignant tumors (it is permitted to register patients with at least 5 years after cure). * Patients who concurrently have any of the following conditions: liver disease such as autoimmune hepatitis, alcoholic liver injury, and drug-induced hepatitis; hemophilia; depression or schizophrenia which requires treatment; hypertension which cannot be controlled by drug therapy or arrhythmia which requires treatment, chronic pulmonary disease; abnormal thyroid function that cannot be controlled by drug therapy; organ transplants (other than corneal, hair transplant, etc.); aldosteronism, myopathy, or hypokalemia. * Patients with a history of hypersensitivity to interferon preparations or biological products such as vaccines * Patients with a history of hypersensitivity to monoammonium glycyrrhizinate, glycine, or L-cysteine monohydrochloride; * Women who are pregnant or lactating, and women in whom pregnancy cannot be ruled out based on the result of serum human chorionic gonadotropin (HCG) measurement at Screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Change in Metavir Fibrosis Score | Baseline and discontinuation of treatment (up to 156 weeks) | Metavir fibrosis score is a 5-point scale based on the amount of fibrosis in the liver, ranging from F0 (best, no fibrosis) to F4 (worst, cirrhosis). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Alanine Aminotransferase (ALT) Normalization of >16 Weeks Duration | Week 24 | The ALT was judged to have been normalized when the ALT level was 35 IU/L or below. |
| Number of Participants With Change in Metavir Inflammation Score | Baseline and Week 48 | Metavir inflammation score is a 4-point scale based on the severity of inflammation in the liver, ranging from A0 (best, no activity) to A3 (worst, severe activity). |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PegIFN-2b Participants receiving peginterferon alfa-2b (PegIFN-2b) at 0.5 ug/kg subcutaneously (SC) once a week for up to 156 weeks. | 125 |
| SNMC Participants receiving stronger neo minophagen C (SNMC) 40 mL by intravenous (IV) injection or IV infusion 3 times weekly for up to 156 weeks. | 127 |
| Total | 252 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Circumstances of site | 1 | 1 |
| Overall Study | Did not meet protocol eligibility | 1 | 0 |
| Overall Study | Irregular visits | 1 | 0 |
| Overall Study | Lack of Efficacy | 4 | 3 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Met discontinuation criteria | 5 | 0 |
| Overall Study | Never received study drug | 2 | 6 |
| Overall Study | Onset of malignant tumor | 11 | 11 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Study discontinuation | 35 | 32 |
| Overall Study | Treatment-related adverse event | 10 | 9 |
| Overall Study | Withdrawal by Subject | 11 | 18 |
Baseline characteristics
| Characteristic | PegIFN-2b | SNMC | Total |
|---|---|---|---|
| Age, Continuous | 59.8 years STANDARD_DEVIATION 9.5 | 60.7 years STANDARD_DEVIATION 8.9 | 60.3 years STANDARD_DEVIATION 9.2 |
| Region of Enrollment Japan | 125 participants | 127 participants | 252 participants |
| Sex: Female, Male Female | 60 Participants | 65 Participants | 125 Participants |
| Sex: Female, Male Male | 65 Participants | 62 Participants | 127 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 125 / 125 | 123 / 127 |
| serious Total, serious adverse events | 32 / 125 | 23 / 127 |
Outcome results
Primary
Number of Participants With Change in Metavir Fibrosis Score
Metavir fibrosis score is a 5-point scale based on the amount of fibrosis in the liver, ranging from F0 (best, no fibrosis) to F4 (worst, cirrhosis).
Time frame: Baseline and discontinuation of treatment (up to 156 weeks)
Population: All treated participants excluding 2 participants on the PegIFN-2B arm and 1 participant on the SNMC arm for whom baseline data were non-evaluable or for whom no post-baseline data were available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PegIFN-2b | Number of Participants With Change in Metavir Fibrosis Score | Participants with ≥1grade lower score (improved) | 13 Participants |
| PegIFN-2b | Number of Participants With Change in Metavir Fibrosis Score | Participants with no change in score | 79 Participants |
| PegIFN-2b | Number of Participants With Change in Metavir Fibrosis Score | Participants with ≥1 grade higher score (worsened) | 31 Participants |
| SNMC | Number of Participants With Change in Metavir Fibrosis Score | Participants with ≥1grade lower score (improved) | 11 Participants |
| SNMC | Number of Participants With Change in Metavir Fibrosis Score | Participants with no change in score | 79 Participants |
| SNMC | Number of Participants With Change in Metavir Fibrosis Score | Participants with ≥1 grade higher score (worsened) | 36 Participants |
Secondary
Number of Participants With Alanine Aminotransferase (ALT) Normalization of >16 Weeks Duration
The ALT was judged to have been normalized when the ALT level was 35 IU/L or below.
Time frame: Week 24
Population: All treated participants except 1 SNMC participant who had no available data after initial treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PegIFN-2b | Number of Participants With Alanine Aminotransferase (ALT) Normalization of >16 Weeks Duration | 9 Participants |
| SNMC | Number of Participants With Alanine Aminotransferase (ALT) Normalization of >16 Weeks Duration | 2 Participants |
Secondary
Number of Participants With Change in Metavir Inflammation Score
Metavir inflammation score is a 4-point scale based on the severity of inflammation in the liver, ranging from A0 (best, no activity) to A3 (worst, severe activity).
Time frame: Baseline and Week 48
Population: All treated participants excluding 3 participants on the PegIFN-2b arm and 1 participant on the SNMC arm for whom baseline data were non-evaluable or for whom no post-baseline data were available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PegIFN-2b | Number of Participants With Change in Metavir Inflammation Score | Participants with ≥1grade lower score (improved) | 48 Participants |
| PegIFN-2b | Number of Participants With Change in Metavir Inflammation Score | Participants with no change in score | 55 Participants |
| PegIFN-2b | Number of Participants With Change in Metavir Inflammation Score | Participants with ≥1grade higher score (worsened) | 19 Participants |
| SNMC | Number of Participants With Change in Metavir Inflammation Score | Participants with ≥1grade lower score (improved) | 23 Participants |
| SNMC | Number of Participants With Change in Metavir Inflammation Score | Participants with no change in score | 61 Participants |
| SNMC | Number of Participants With Change in Metavir Inflammation Score | Participants with ≥1grade higher score (worsened) | 42 Participants |