Hepatitis C, Chronic
Conditions
Keywords
chronic hepatitis C, pegylated interferon alfa-2b, ribavirin, Australia
Brief summary
This is an Australian, open-label, multicenter, randomized, double-blind clinical trial designed to assess the efficacy of combination therapy with pegylated interferon alfa-2b and ribavirin for 48 weeks versus 24 weeks in the treatment of chronic hepatitis C (treatment-naïve genotype 3 subjects with high viral loads who have a METAVIR score of at least F1A2). The primary endpoint will be a sustained virological response defined by undetectable HCV RNA in serum at 24 weeks after completion of therapy.
Interventions
BIOLOGICALPeginterferon alfa-2b
Powder for injection in Redipen (50, 80, 100, 120 and 150 microgram strengths), subcutaneous, dose of 1.5 micrograms/kg, weekly for up to 24 weeks
DRUGRibavirin
200 mg capsules, oral, weight-based dose of 800, 1000, or 1200 mg, daily for up to 24 weeks
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Comply with all current Australian Schedule of Pharmaceutical Benefits S100 eligibility criteria. * Chronic hepatitis C genotype 3 infection with a viral load of at least 2 million copies per mL. * Able to give written informed consent. * Understand and be able to adhere to the dosing and visit schedules. * Compensated liver disease with the following minimum hematologic and biochemical criteria: * Hemoglobin ≥120 g/L (females), ≥130 g/L (males) * Platelets ≥100 x 10\^9/L * Neutrophil count ≥1.5 x 10\^9/L * Creatinine clearance \>50 mL/minute * Thyroid stimulating hormone (TSH) within normal limits * Serum hepatitis B surface antigen (HBsAg) and human immunodeficiency virus (HIV) negative. * Negative pregnancy test.
Exclusion criteria
* Suspected hypersensitivity to interferon, pegylated interferon alfa-2b, or ribavirin. * Participation in any other investigational drug program within 30 days of the screening visit for this protocol. * Any cause of liver disease based on patient history and biopsy other than chronic hepatitis C, including but not limited to: hemochromatosis, alpha-1 antitrypsin deficiency, Wilson's disease, autoimmune hepatitis, alcoholic liver disease, drug-related liver disease. * Hepatocellular carcinoma. * Decompensated cirrhosis (ascites, history of encephalopathy or bleeding varices, serum albumin \<35 g/L, prothrombin time (PT) prolonged by greater than 3 sec). * Significant cardiovascular dysfunction within the past 6 months (e.g., angina, congestive heart failure, myocardial infarction, severe hypertension, or significant arrhythmia) or participants with an ECG showing clinically significant abnormalities. * Immunologically-mediated disease, (e.g. inflammatory bowel disease), idiopathic thrombocytopenic purpura, systemic lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis). * Hemophilia or any hemoglobinopathy, including but not limited to thalassemia major. * Severe psychiatric condition, including major depression, a history of major psychoses, current suicidal ideation, and/or suicidal attempts. * Ongoing substance abuse, e.g. alcohol, I.V. drugs or inhalants that in the opinion of the investigator would jeopardize the patient's ability to comply with study requirements. * Clinically significant ophthalmological disorders. * Treatment or recent treatment with immunosuppressive agents (excluding short-term corticosteroid withdrawal) and immunosuppressed transplant recipients. * Poorly controlled thyroid disease. * Any other condition that in the opinion of the investigator would make the patient unsuitable for enrolment, or could interfere with the patient participating in and completing the clinical trial program.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sustained Virological Response (SVR), Defined by Undetectable HCV RNA in Serum at 24 Weeks After Completion of Therapy | 24 weeks after completion of either up to 24 or 48 weeks of therapy | No formal comparisons could be made and no conclusions drawn because of small numbers in the treatment groups; a result of an inability to fulfill the recruitment target. |
Participant flow
Recruitment details
The target recruitment was not attained within the anticipated study time-frame and so study recruitment was ceased on 24 November 2006; however those patients already enrolled in the study continued in the study until completion.
Pre-assignment details
Enrolled 146 subjects; 143 subjects were treated; 3 subjects were withdrawn at Baseline and never received study medication: 1 subject in the 24 weeks group due to consent issues; and 2 subjects in the 48 weeks group (1 subject was ineligible and 1 subject was randomized in error).
Participants by arm
| Arm | Count |
|---|---|
| 24 Weeks of Therapy Genotype 3 HCV subjects with high viral load (at least 2 million copies/mL) treated for 24 weeks | 79 |
| 48 Weeks of Therapy Genotype 3 HCV subjects with high viral load (at least 2 million copies/mL) treated for 48 weeks | 64 |
| Total | 143 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 15 | 38 |
Baseline characteristics
| Characteristic | 24 Weeks of Therapy | 48 Weeks of Therapy | Total |
|---|---|---|---|
| Age, Continuous | 40.9 years STANDARD_DEVIATION 9.2 | 40.5 years STANDARD_DEVIATION 9.8 | 40.7 years STANDARD_DEVIATION 9.44 |
| Sex/Gender, Customized Female | 27 participants | 12 participants | 39 participants |
| Sex/Gender, Customized Male | 52 participants | 51 participants | 103 participants |
| Sex/Gender, Customized Transgender | 0 participants | 1 participants | 1 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 79 / 79 | 64 / 64 |
| serious Total, serious adverse events | 8 / 79 | 9 / 64 |
Outcome results
Primary
Sustained Virological Response (SVR), Defined by Undetectable HCV RNA in Serum at 24 Weeks After Completion of Therapy
No formal comparisons could be made and no conclusions drawn because of small numbers in the treatment groups; a result of an inability to fulfill the recruitment target.
Time frame: 24 weeks after completion of either up to 24 or 48 weeks of therapy
Population: Data were missing for 1 subject in the 48 weeks of therapy treatment arm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 24 Weeks of Therapy | Sustained Virological Response (SVR), Defined by Undetectable HCV RNA in Serum at 24 Weeks After Completion of Therapy | 55 Participants |
| 48 Weeks of Therapy | Sustained Virological Response (SVR), Defined by Undetectable HCV RNA in Serum at 24 Weeks After Completion of Therapy | 36 Participants |