Hepatitis C, Chronic
Conditions
Keywords
chronic hepatitis C, pegylated interferon alfa-2b, ribavirin, Asia
Brief summary
This is a multicenter clinical trial designed to compare the efficacy of 48 weeks of therapy with pegylated (PEG)-Interferon/ribavirin in Southeastern Asian patients with genotype 1 chronic hepatitis C with 48 weeks of therapy with PEG-Interferon/ribavirin in Caucasian patients with genotype 1 chronic hepatitis C. This study is also designed to provide a randomized comparison of 24 weeks versus 48 weeks of therapy with PEG-Interferon/ribavirin in Southeastern Asian patients with genotypes 6-9. The primary endpoint is sustained virologic response, as defined by negative hepatitis C virus (HCV) ribonucleic acid (RNA) in serum at 24 weeks after therapy completion.
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 48 weeks
DRUGribavirin
200 mg capsules, oral, weight-based dose of 800, 1000, or 1200 mg daily for up to 48 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. * Able to give written informed consent and adhere to study visit schedule. * South East Asian ethnicity (except for Caucasian Gt1/1b in comparator arm) i.e. born in Vietnam, Cambodia, Laos, Thailand, Hong Kong, and China or have both parents born in these countries. * Genotype 1, 1a, 1b, 6, 6a, 6b, 7, 8, or 9, as classified by INNO-LiPA assay. * Hemoglobin \>=120 g/L (females), \>=130 g/L (males). * Platelet count \>=100 x 10\^9/L. * Neutrophil count \>=1.5 x 10\^9/L. * Negative pregnancy test for females. * Thyroid stimulating hormone (TSH) within normal limits.
Exclusion criteria
* Participation in any other investigational drug program within 30 days of the Screening Visit. * Human immunodeficiency virus (HIV) antibody positive or hepatitis B surface antigen (HBsAg) positive. * Genotype 2, 3, 4, or 5, as classified by INNO-LiPA assay. * Non South East Asian ethnicity (unless recruited to Caucasian GT1 comparator arm). * Evidence of liver disease due to other disorders (e.g., hemachromatosis, Wilson's disease). * Ongoing drug or alcohol abuse which in the opinion of the investigator would jeopardize the patient's ability to comply with study requirements. * Inability to comply with study requirements for other reasons. * Decompensated cirrhosis (Ascites, history of encephalopathy or bleeding varices, serum albumin \<35 g/L, prothrombin time (PT) prolonged by greater than 3 sec). * Present or prior history of severe psychiatric disease requiring hospitalization or medication. * History of severe seizure disorder. * History of autoimmune disorders (e.g., rheumatoid arthritis, inflammatory bowel disease, immune thrombocytopenic purpura, systemic lupus erythematosus, or other mixed connective tissue disease, psoriasis, optic neuritis). * Poorly controlled thyroid disease. * Creatinine clearance \<50 mL/min. * Severe cardiovascular disease. * Hepatocellular cancer. * Clinically significant ophthalmologic disorders. * Hemoglobinopathies (e.g., thalassemia, sickle-cell anemia). * Treatment or recent treatment with immunosuppressive agents (excluding short-term corticosteroid withdrawal), and immunosuppressed transplant recipients scheme.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Who Achieved a Sustained Virologic Response (SVR) | 24 weeks after completion of either up to 24 or 48 weeks of therapy | SVR is defined as negative hepatitis C virus ribonucleic acid (HCV RNA) in serum at 24 weeks after therapy completion. The study was terminated early due to slow enrollment. The primary outcome measure could not be assessed. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Genotype 1 SEA PEG-IFN/RIB 48 w Genotype 1 hepatitis C virus (HCV)-infected Southeastern Asian (SEA) subjects treated for up to 48 weeks with PegIntron (peginterferon alfa-2b; PEG-IFN) REDIPEN and REBETOL (ribavirin; RIB) combination therapy | 45 |
| Genotype 1 Caucasian PEG-IFN/RIB 48 w Genotype 1 HCV-infected Caucasian subjects treated for up to 48 weeks with PEG-Intron REDIPEN and REBETOL combination therapy | 9 |
| Genotype 6, 7, 8, 9 SEA PEG-IFN/RIB 24 w Genotype 6, 7, 8, 9 HCV-infected SEA subjects randomized to treatment for 24 weeks with PEG-Intron REDIPEN and REBETOL combination therapy | 33 |
| Genotype 6, 7, 8, 9 SEA PEG-IFN/RIB 48 w Genotype 6, 7, 8, 9 HCV-infected SEA subjects randomized to treatment for 48 weeks with PEG-Intron REDIPEN and REBETOL combination therapy | 34 |
| Total | 121 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 2 | 0 |
| Overall Study | Adverse lab experience | 1 | 0 | 0 | 0 |
| Overall Study | Did not meet viral reduction criteria | 4 | 5 | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 | 1 | 2 |
| Overall Study | Other | 7 | 0 | 3 | 2 |
| Overall Study | Sponsor request | 18 | 3 | 8 | 17 |
| Overall Study | Withdrew consent | 0 | 0 | 2 | 0 |
Baseline characteristics
| Characteristic | Genotype 1 SEA PEG-IFN/RIB 48 w | Genotype 1 Caucasian PEG-IFN/RIB 48 w | Genotype 6, 7, 8, 9 SEA PEG-IFN/RIB 24 w | Genotype 6, 7, 8, 9 SEA PEG-IFN/RIB 48 w | Total |
|---|---|---|---|---|---|
| Age, Continuous | 43.6 years STANDARD_DEVIATION 11.06 | 43.6 years STANDARD_DEVIATION 12.3 | 46.8 years STANDARD_DEVIATION 10.56 | 46.3 years STANDARD_DEVIATION 10.71 | 45.2 years STANDARD_DEVIATION 10.89 |
| Sex: Female, Male Female | 19 Participants | 4 Participants | 15 Participants | 12 Participants | 50 Participants |
| Sex: Female, Male Male | 26 Participants | 5 Participants | 18 Participants | 22 Participants | 71 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 42 / 45 | 9 / 9 | 32 / 33 | 32 / 34 |
| serious Total, serious adverse events | 2 / 45 | 0 / 9 | 3 / 33 | 1 / 34 |
Outcome results
Primary
Number of Subjects Who Achieved a Sustained Virologic Response (SVR)
SVR is defined as negative hepatitis C virus ribonucleic acid (HCV RNA) in serum at 24 weeks after therapy completion. The study was terminated early due to slow enrollment. The primary outcome measure could not be assessed.
Time frame: 24 weeks after completion of either up to 24 or 48 weeks of therapy
Population: The study was terminated early due to slow enrollment. The primary outcome measure should be assessed with caution. No data was available at 24 weeks after therapy for the Genotype 1 Caucasian treatment group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Genotype 1 SEA PEG-IFN/RIB 48 w | Number of Subjects Who Achieved a Sustained Virologic Response (SVR) | 4 Participants |
| Genotype 6, 7, 8, 9 SEA PEG-IFN/RIB 24 w | Number of Subjects Who Achieved a Sustained Virologic Response (SVR) | 13 Participants |
| Genotype 6, 7, 8, 9 SEA PEG-IFN/RIB 48 w | Number of Subjects Who Achieved a Sustained Virologic Response (SVR) | 7 Participants |
95% CI: [28.36, 99.49]
95% CI: [50.1, 93.19]
95% CI: [47.35, 99.48]