Hepatitis B, Chronic (CHB)
Conditions
Keywords
Hepatitis B virus, Pegylated interferon alfa-2b (PegIntron)
Brief summary
This is an open label, randomized, comparative, multi-center study. Subjects will be screened within 2 weeks prior to study entry to establish eligibility. Subjects who meet all the selection criteria will be randomly assigned 1:1 to (1) once-a-week, subcutaneous Pegylated interferon alfa-2b (PegIntron) (1.5 mcg/kg body weight) or (2) oral adefovir 10 mg daily. The treatment phase will be 24 weeks for PegIntron and 48 weeks for adefovir. All subjects completing the assigned treatment phase will be followed up for an additional 48 weeks for PegIntron and 24 weeks for adefovir as observation phase. The primary objective is to establish the efficacy profile of PegIntron. Secondary objectives are to compare the efficacy profile of PegIntron with that of adefovir, compare efficacy of PegIntron in lamivudine-naïve and lamivudine-experienced subjects, and to establish the safety profile of PegIntron in treating patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B.
Interventions
BIOLOGICALPegylated interferon alfa-2b (PegIntron)
Powder for injection in vials ( 100, and 120 microgram strengths), subcutaneous, dose of 1.5 micrograms/kg, weekly for up to 24 weeks
DRUGAdefovir dipivoxil (adefovir)
10 mg adefovir dipivoxil (equivalent to 5.4.5 mg adefovir) tablets, oral, dose of 1 tablet per day 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 70 Years
Healthy volunteers
No
Inclusion criteria
* Adult male or female, 18 to 70 years of age. * Documented positive serum hepatitis B surface antigen (HBsAg) for a minimum of 6 months prior to randomization. * Hepatitis B virus (HBV) replication and hepatitis documented by: * Serum HBV DNA (Hepatitis B Virus Deoxyribonucleic acid) \>= 10\^5 copies/mL within 3 months prior to entry * Positive serum hepatitis B e antigen (HBeAg) within 3 months prior to entry * Documented presence of ALT (Alanine Aminotransferase) twice (1 month apart) within 3 months prior to entry (2 to 10 folds above the upper normal level) * Liver biopsy finding shows evidence of chronic hepatitis without liver cirrhosis, document acceptable if no anti-HBV treatment within 1 year prior to randomization * Naïve or exposed to lamivudine (3 months treatment-free interval prior to randomization) * Adequate renal function (creatinine within normal upper limit). * Compensated liver disease with certain minimum hematological and serum biochemical criteria. * Thyroid stimulating hormone (TSH) and free T4 within normal ranges. * Negative antibody to hepatitis C and hepatitis D. * Negative antibody to human immunodeficiency virus. * Negative evidence for hepatocellular carcinoma by alfa-fetoprotein and ultrasound within 1 month prior to randomization.
Exclusion criteria
* Women who are pregnant or nursing. * Prior treatment for hepatitis with any interferon or adefovir, or other investigational anti-virus agents. * Prior treatment for hepatitis with immunomodulatory drug within 2 years prior to randomization. * Suspected hypersensitivity to interferon or adefovir. * Liver cirrhosis. * History of severe psychiatric disease, especially depression. * Concurrent malignancies (including hepatocellular carcinoma). * Unstable or significant cardiovascular diseases. * Prolonged exposure to known hepatotoxins. * History of thyroid disease poorly controlled on prescribed medication. * Poorly controlled diabetes mellitus. * Have suspected or confirmed significant hepatic disease from an etiology other than HBV. * Severe renal disease or myeloid dysfunction. * History of organ transplantation other than cornea and hair transplant. * Any medical condition requiring chronic systemic administration of steroids.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Combined Response Consisting of All Three Responses - (a) Serological Response, (b) Virological Response, and (c) Biochemical Response | At Week 72 [for Pegylated interferon alfa-2b (PegIntron), at 48 weeks post PegIntron treatment for up to 24 weeks; for Adefovir, at 24 weeks post adefovir treatment for up to 48 weeks] | 1. Serological response is defined as Loss of HBeAg (Hepatitis B e antigen) and Appearance of anti-HBe (Hepatitis B e antibodies); participant is HBeAg negative and anti-HBe positive. 2. Virological response was defined as having \< 10\^5 copies/mL of serum HBV DNA (Hepatitis B Virus Deoxyribonucleic Acid) by real-time PCR (Polymerase Chain Reaction). 3. Biochemical response was defined as acheiving normal levels of ALT (Alanine Aminotransferase) level in Units/L. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PegIntron PegIntron, 1.5 micrograms/kg weekly, for up to 24 weeks followed by a 48-week observation phase | 13 |
| Adefovir Adefovir, 10 mg daily, for up to 48 weeks followed by a 24-week observation phase | 12 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Investigator Judgment | 2 | 3 |
| Overall Study | Study termination | 4 | 3 |
| Overall Study | Withdrawal by Subject | 1 | 3 |
Baseline characteristics
| Characteristic | PegIntron | Adefovir | Total |
|---|---|---|---|
| Age, Continuous | 36.7 years STANDARD_DEVIATION 8.5 | 36.7 years STANDARD_DEVIATION 13.6 | 36.7 years STANDARD_DEVIATION 11 |
| Region of Enrollment Taiwan, Province Of China | 13 participants | 12 participants | 25 participants |
| Sex: Female, Male Female | 4 Participants | 1 Participants | 5 Participants |
| Sex: Female, Male Male | 9 Participants | 11 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 13 / 13 | 8 / 12 |
| serious Total, serious adverse events | 1 / 13 | 0 / 12 |
Outcome results
Primary
Number of Participants With a Combined Response Consisting of All Three Responses - (a) Serological Response, (b) Virological Response, and (c) Biochemical Response
1. Serological response is defined as Loss of HBeAg (Hepatitis B e antigen) and Appearance of anti-HBe (Hepatitis B e antibodies); participant is HBeAg negative and anti-HBe positive. 2. Virological response was defined as having \< 10\^5 copies/mL of serum HBV DNA (Hepatitis B Virus Deoxyribonucleic Acid) by real-time PCR (Polymerase Chain Reaction). 3. Biochemical response was defined as acheiving normal levels of ALT (Alanine Aminotransferase) level in Units/L.
Time frame: At Week 72 [for Pegylated interferon alfa-2b (PegIntron), at 48 weeks post PegIntron treatment for up to 24 weeks; for Adefovir, at 24 weeks post adefovir treatment for up to 48 weeks]
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PegIntron | Number of Participants With a Combined Response Consisting of All Three Responses - (a) Serological Response, (b) Virological Response, and (c) Biochemical Response | 0 Participants |
| Adefovir | Number of Participants With a Combined Response Consisting of All Three Responses - (a) Serological Response, (b) Virological Response, and (c) Biochemical Response | 0 Participants |