Hepatitis C
Conditions
Brief summary
This study will determine the efficacy of PEG-Intron (SCH 54031) in participants with chronic Hepatitis C virus (HCV) infection who have not been previously treated with interferon. Participants are randomized to receive one of three doses of PEG-Intron (0.5, 1.0, and 1.5 mg/kg) or Interferon Alfa-2B for 48 weeks. The primary objective of this study is to evaluate the efficacy of PEG-Intron (compared to Interferon Alfa-2B) with respect to response based on loss of detectable HCV ribonucleic acid (HCV-RNA) and normalization of alanine transaminase (ALT) level after 24 weeks of therapy and at 24 weeks of follow-up.
Interventions
BIOLOGICALPEG-Intron
PEG-Intron is administered QW for 48 weeks by SC injection at 0.5, 1.0, and 1.5 mg/kg body weight. Body weight obtained at the baseline visit is used to calculate dosing.
BIOLOGICALInterferon Alfa-2B
Interferon alfa-2b is administered TIW for 48 weeks by SC injection at 3 MIU regardless of participant body weight.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Be serum positive for hepatitis C virus. * Have liver biopsy within 1 year prior to entry, with a pathology report confirming a histological diagnosis consistent with chronic hepatitis. * Have one abnormal historic ALT at least 6 months prior to screening, with elevated ALT at entry. * Have compensated liver disease, testing negative for HIV and serum hepatitis B surface antigen (HBsAg) at entry. * If male or female of childbearing potential, be practicing adequate contraception during treatment.
Exclusion criteria
* Be female who is currently pregnant or nursing. * Have prior treatment with any interferon. * Have suspected hypersensitivity to alpha interferon. * Have participated in any other clinical trial within 30 days of entry * Have received treatment with any investigational drug within 30 days of entry. * Have received prior treatment for hepatitis with any other antiviral or immunomodulatory drug within the previous 2 years. * Have any other cause for the liver disease other than chronic hepatitis C including but not limited to: co-infection with hepatitis B virus; Hemochromatosis; alpha-1 antitrypsin deficiency; Wilson's disease; autoimmune hepatitis; alcoholic liver disease; obesity-induced liver disease; and drug-related liver disease. * Have hemophilia or any other condition that would prevent the participant from having a liver biopsy, including anticoagulant therapy. * Have hemoglobinopathies (e.g., Thalassemia) * Have evidence of advanced liver disease such as history or presence of ascites, bleeding varices, spontaneous encephalopathy. * Have received organ transplants. * Have a preexisting psychiatric condition, especially severe depression, or a history of severe psychiatric disorder, such as major psychoses, suicidal ideation and/or attempt. * Have central nervous system trauma or active seizure disorders requiring medication. * Have significant cardiovascular dysfunction within the past 6 months (e.g., angina, congestive heart failure, recent myocardial infarction, severe hypertension or significant arrhythmia). * Have poorly controlled diabetes mellitus. * Have chronic pulmonary disease (e.g., chronic obstructive pulmonary disease). * Have immunologically mediated disease (e.g., inflammatory bowel disease \[Crohn's disease, ulcerative colitis\], rheumatoid arthritis, idiopathic thrombocytopenia purpura, systemic lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis, clinical cryoglobulinemia with vasculitis). * Have any medical condition requiring, or likely to require during the course of the study, chronic systemic administration of steroids. * Have history of substance abuse, such as alcohol, intravenous drugs and inhaled drugs. * Have clinically significant retinal abnormalities. * Be unable to abstain from the consumption of alcohol. * Have any other condition which in the opinion of the investigator would make the patient unsuitable for enrollment, or could interfere with the patient participating in and completing the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Achieving Responder Status at 24 Weeks of Treatment | Up to 24 weeks | The number of participants achieving responder status at 24 weeks of treatment was assessed. A participant was classified as a responder if, at 24 weeks of treatment, they met both of the following criteria: 1) HCV-Ribonucleic Acid (RNA) negative (defined as \<100 copies/mL serum by quantitative polymerase chain reaction \[qPCR\] assay); and 2) alanine transaminase (ALT) level normal. |
| Number of Participants Achieving Sustained Responder Status at 24 Weeks of Follow-up | Up to 72 weeks (up to 48 weeks treatment and 24 weeks follow-up) | The number of participants achieving sustained responder status at 24 weeks of follow-up was assessed. A participant was classified as a sustained responder if, at 24 weeks of follow-up, they met both of the following criteria: 1) HCV-RNA negative (defined as \<100 copies/mL serum by qPCR assay); and 2) ALT level normal. |
Participant flow
Recruitment details
In total, 1224 participants with chronic Hepatitis C virus (HCV) infection were randomized, with 1219 receiving study treatment.
Participants by arm
| Arm | Count |
|---|---|
| PEG-Intron, 0.5 mg/kg PEG-Intron administered QW for 48 weeks at 0.5 mg/kg by SC injection. | 315 |
| PEG-Intron, 1.0 mg/kg PEG-Intron administered QW for 48 weeks at 1.0 mg/kg by SC injection. | 297 |
| PEG-Intron, 1.5 mg/kg PEG-Intron administered QW for 48 weeks at 1.5 mg/kg by SC injection. | 304 |
| Interferon Alfa-2b Interferon Alfa-2b administered TIW for 48 weeks at 3 MIU by SC injection. | 303 |
| Total | 1,219 |
Baseline characteristics
| Characteristic | PEG-Intron, 0.5 mg/kg | PEG-Intron, 1.0 mg/kg | PEG-Intron, 1.5 mg/kg | Interferon Alfa-2b | Total |
|---|---|---|---|---|---|
| Age, Continuous | 43.1 Years STANDARD_DEVIATION 9.4 | 43.7 Years STANDARD_DEVIATION 9.5 | 42.9 Years STANDARD_DEVIATION 8.7 | 42.6 Years STANDARD_DEVIATION 9.2 | 43.1 Years STANDARD_DEVIATION 9.2 |
| Sex: Female, Male Female | 130 Participants | 109 Participants | 114 Participants | 96 Participants | 449 Participants |
| Sex: Female, Male Male | 185 Participants | 188 Participants | 190 Participants | 207 Participants | 770 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 | 1 / 315 | 0 / 297 | 0 / 304 | 2 / 303 |
| other Total, other adverse events | 306 / 315 | 291 / 297 | 296 / 304 | 293 / 303 |
| serious Total, serious adverse events | 37 / 315 | 32 / 297 | 31 / 304 | 29 / 303 |
Outcome results
Primary
Number of Participants Achieving Responder Status at 24 Weeks of Treatment
The number of participants achieving responder status at 24 weeks of treatment was assessed. A participant was classified as a responder if, at 24 weeks of treatment, they met both of the following criteria: 1) HCV-Ribonucleic Acid (RNA) negative (defined as \<100 copies/mL serum by quantitative polymerase chain reaction \[qPCR\] assay); and 2) alanine transaminase (ALT) level normal.
Time frame: Up to 24 weeks
Population: Includes all randomized participants receiving ≥1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PEG-Intron, 0.5 mg/kg | Number of Participants Achieving Responder Status at 24 Weeks of Treatment | 80 Participants |
| PEG-Intron, 1.0 mg/kg | Number of Participants Achieving Responder Status at 24 Weeks of Treatment | 87 Participants |
| PEG-Intron, 1.5 mg/kg | Number of Participants Achieving Responder Status at 24 Weeks of Treatment | 90 Participants |
| Interferon Alfa-2b | Number of Participants Achieving Responder Status at 24 Weeks of Treatment | 59 Participants |
p-value: 0.078Chi-squared
p-value: 0.005Chi-squared
p-value: 0.004Chi-squared
Primary
Number of Participants Achieving Sustained Responder Status at 24 Weeks of Follow-up
The number of participants achieving sustained responder status at 24 weeks of follow-up was assessed. A participant was classified as a sustained responder if, at 24 weeks of follow-up, they met both of the following criteria: 1) HCV-RNA negative (defined as \<100 copies/mL serum by qPCR assay); and 2) ALT level normal.
Time frame: Up to 72 weeks (up to 48 weeks treatment and 24 weeks follow-up)
Population: Includes all randomized participants receiving ≥1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PEG-Intron, 0.5 mg/kg | Number of Participants Achieving Sustained Responder Status at 24 Weeks of Follow-up | 52 Participants |
| PEG-Intron, 1.0 mg/kg | Number of Participants Achieving Sustained Responder Status at 24 Weeks of Follow-up | 70 Participants |
| PEG-Intron, 1.5 mg/kg | Number of Participants Achieving Sustained Responder Status at 24 Weeks of Follow-up | 69 Participants |
| Interferon Alfa-2b | Number of Participants Achieving Sustained Responder Status at 24 Weeks of Follow-up | 37 Participants |
p-value: 0.128Chi-squared
p-value: <0.001Chi-squared
p-value: <0.001Chi-squared