Hepatitis C, Chronic
Conditions
Keywords
hepatitis C
Brief summary
The objective is to evaluate the efficacy and safety of the combination therapy with subcutaneous (SC) Pegylated Interferon (PEG-IFN) alfa-2b 1.5 ug/kg/week plus low-dose ribavirin administered for 48 weeks in participants with chronic hepatitis C virus (HCV) who are infected with HCV genotype 1 high viral load, and weigh 50 kg or less.
Interventions
BIOLOGICALPegylated Interferon alfa-2b
Pegylated Interferon alfa-2b 1.5 ug/kg SC once weekly for 48 weeks
DRUGRibavirin
Ribavirin 400 mg/day orally
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 No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosed with chronic hepatitis C. * Minimum 20 years of age * Willing to use adequate contraception during the course of the study. * Participants who can be hospitalized for at least 14 days since treatment initiation. * Positive for HCV genotype 1 (genotype 1a and 1b) with high viral load (HCV-RNA \>=100 kIU/mL). * Participants weighing over 40 kg to 50 kg. * Hematology results of: * hemoglobin levels \>=12 g/dL * neutrophils \>=1,500/mm\^3 * platelets \>=100,000/mm\^3
Exclusion criteria
* Previous ribavirin therapy. * Previous interferon therapy within 90 days of registration. * Participants who received treatment with injectable products containing glycyrrhizin/cysteine/glycine (Stronger Neo-Minophagen C, etc.), Shosaikoto, or ursodeoxycholic acid within 30 days before the start of treatment * Participants who received treatment with an antiviral or anti-tumor drug or who received immunomodulating therapy (including steroids and radiotherapy) within 90 days before the start of treatment \[excluding local administration and topical drugs\]. * Participants who received other investigational drugs within 180 days before the start of treatment. * Hepatitis Bs (HBs) antigen-positive * Antinuclear antibodies \>=1:160 * Fasting blood glucose \>=110 mg/dL (however, participants with fasting blood glucose of 110 mg/dL to \<126 mg/dL can be registered if HbA1c is \<6.5%) * Participants diagnosed with liver cirrhosis in most recent celioscopy or liver biopsy. * Participants with or who have a history of any of the following: liver failure; hepatic encephalopathy, esophageal varices, or ascites; depression or schizophrenia requiring treatment or suicidal attempt or ideation; epileptic seizures requiring drug treatment; autoimmune disease (such as Hashimoto's disease, Crohn's disease, ulcerative colitis, chronic rheumatoid arthritis, idiopathic thrombocytopenic purpura, systemic erythematosus, autoimmune hemolytic anemia, and scleroderma); hepatic cancer * Participants with any of the following: liver disease such as autoimmune hepatitis, alcoholic liver disease, and drug-induced hepatic impairment; hemophilia; arrhythmia requiring treatment and participants with or who have a history of angina pectoris, cardiac failure, myocardial infarction, or life-threatening arrhythmia; hypertension (systolic BP of 160 mmHg or more and diastolic BP of 100 mmHg or more) not possible to control with drug therapy; chronic pulmonary disease; hemoglobinopathy (thalassemia, sickle cell anemia); malignant tumor or who have a history of malignant tumor within the past 5 years; thyroid function disorder not controlled by drug therapy. * Participants with organ transplants (excluding cornea and hair transplants). * Participants with a history of hypersensitivity to interferon preparations, nucleoside analogs, or biological products such as vaccine. * Participants with a specific response to PEG-IFN alfa-2b in a prick test to be conducted just before the initiation of treatment. * Participants who are pregnant or nursing (in the case of male Participants : partner is pregnant)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response (SVR) at 24 Weeks After the End of Treatment (EOT) or Discontinuation | Measured at 24 weeks after the end of treatment (at the end of follow-up) | SVR was defined as a viral response which was sustained at 24 weeks after the end of treatment as measured by Hepatitis C Virus Ribonucleic Acid (HCV-RNA) negativity. HCV-RNA negativity was assessed by an reverse transcriptase polymerase chain reaction (RT-PCR) method, where a negative response was defined by a negative qualitative HCV-RNA result. |
| Number of Participants Discontinuing Treatment | From time of first treatment to Week 48 | Prespecified adverse event discontinuance criteria included neutrophil count \<500 /mm3, platelet count \<50,000/mm3, and hemoglobin \<8.5 g/dL. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HCV-RNA Negativity at 24 Weeks of Treatment and at EOT | Measured at 24 weeks of treatment and at EOT (Treatment week 48) | HCV-RNA negativity was assessed by an RT-PCR method, where a negative response was defined by a negative qualitative HCV-RNA result. |
Participant flow
Pre-assignment details
Participants could be discontinued from study by meeting prespecified AE discontinuance criteria defined in the protocol. Prespecified adverse event discontinuance criteria included neutrophil count \<500 /mm3, platelet count \<50,000/mm3, and hemoglobin \<8.5 g/dL
Participants by arm
| Arm | Count |
|---|---|
| PEG-IFN + Ribavirin PEG-IFN was administered to participants at 1.5 μg/kg subcutaneously once weekly for 48 weeks. Ribavirin was administered orally every day after morning and evening meals for 48 weeks at 400 mg/day. | 75 |
| Total | 75 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Discontinuance Criteria (specified AEs) | 4 |
| Overall Study | No Visit | 1 |
| Overall Study | Pregnancy | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | PEG-IFN + Ribavirin |
|---|---|
| Age, Continuous | 55.1 years STANDARD_DEVIATION 9.7 |
| Age, Customized < 65 yrs | 64 participants |
| Age, Customized ≥ 65 yrs | 11 participants |
| Sex: Female, Male Female | 70 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 75 / 75 |
| serious Total, serious adverse events | 7 / 75 |
Outcome results
Primary
Number of Participants Discontinuing Treatment
Prespecified adverse event discontinuance criteria included neutrophil count \<500 /mm3, platelet count \<50,000/mm3, and hemoglobin \<8.5 g/dL.
Time frame: From time of first treatment to Week 48
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PEG-IFN + Ribavirin | Number of Participants Discontinuing Treatment | Due To Decrease in Neutrophil Count | 3 participants |
| PEG-IFN + Ribavirin | Number of Participants Discontinuing Treatment | Due To Decrease in Neutrophil and Platelet Count | 1 participants |
| PEG-IFN + Ribavirin | Number of Participants Discontinuing Treatment | Due To Apathy | 1 participants |
| PEG-IFN + Ribavirin | Number of Participants Discontinuing Treatment | Due To Pleural Effusion | 1 participants |
| PEG-IFN + Ribavirin | Number of Participants Discontinuing Treatment | Due To Pregnancy of Participant's Partner | 1 participants |
| PEG-IFN + Ribavirin | Number of Participants Discontinuing Treatment | Due To No Visit | 1 participants |
| PEG-IFN + Ribavirin | Number of Participants Discontinuing Treatment | Due To Withdrawal by Subject | 2 participants |
| PEG-IFN + Ribavirin | Number of Participants Discontinuing Treatment | Total Number Discontinued | 10 participants |
Primary
Percentage of Participants With Sustained Virologic Response (SVR) at 24 Weeks After the End of Treatment (EOT) or Discontinuation
SVR was defined as a viral response which was sustained at 24 weeks after the end of treatment as measured by Hepatitis C Virus Ribonucleic Acid (HCV-RNA) negativity. HCV-RNA negativity was assessed by an reverse transcriptase polymerase chain reaction (RT-PCR) method, where a negative response was defined by a negative qualitative HCV-RNA result.
Time frame: Measured at 24 weeks after the end of treatment (at the end of follow-up)
Population: All treated Participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PEG-IFN + Ribavirin | Percentage of Participants With Sustained Virologic Response (SVR) at 24 Weeks After the End of Treatment (EOT) or Discontinuation | 30.7 percentage of participants |
Secondary
Percentage of Participants With HCV-RNA Negativity at 24 Weeks of Treatment and at EOT
HCV-RNA negativity was assessed by an RT-PCR method, where a negative response was defined by a negative qualitative HCV-RNA result.
Time frame: Measured at 24 weeks of treatment and at EOT (Treatment week 48)
Population: All treated Participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PEG-IFN + Ribavirin | Percentage of Participants With HCV-RNA Negativity at 24 Weeks of Treatment and at EOT | At 24 Weeks Treatment | 61.3 percentage of participants |
| PEG-IFN + Ribavirin | Percentage of Participants With HCV-RNA Negativity at 24 Weeks of Treatment and at EOT | At End of Treatment | 66.7 percentage of participants |