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A Study of the Safety and Efficacy of Pegylated Inferferon Alfa-2b (PEG-Intron™) Versus Pegylated Interferon Alfa-2a (PEGASYS™) in Participants With Chronic Hepatitis B (P08450)

Phase 3
Terminated
Conditions
Hepatitis B, Chronic
Interventions
Biological: PEG-Intron™
Biological: PEGASYS™
Registration Number
NCT01641926
Lead Sponsor
Merck Sharp & Dohme LLC
Brief Summary

This study is being done to compare the safety and efficacy of PEG-Intron™ to that of PEGASYS™ in participants with chronic hepatitis B (hepatitis B envelope antigen \[HBeAg\] positive or negative) who have not previously been treated with interferon.

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
402
Inclusion Criteria
  • Must be able to adhere to dose and visit schedules
  • ≥ 40 kg
  • Hepatitis B surface antigen (HBsAg) positive for at least 6 months
  • Anti-HBs negative
  • Female participants of childbearing potential must agree to use an acceptable

method of contraception from at least 2 weeks prior to Day 1 and continue until at least 1 month after last dose of study drug

Inclusion Criteria for HBeAg(+) participants:

  • HBeAg(+)
  • Anti-HBe(-)

Inclusion Criteria for HBeAg(-) participants:

  • HBeAg(-)
  • Anti-HBe(+)
Exclusion Criteria
  • Co-infection with the human immunodeficiency virus (HIV) or hepatitis C or hepatitis D virus
  • Prior treatment with interferon for hepatitis B
  • Use of nucleoside/nucleotide analogues within 6 months of the screening visit or at any time during the study
  • Use of any investigational drug within 30 days of the screening visit
  • Prior treatment with herbal remedies with known hepatotoxicity. All herbal remedies used for hepatitis B treatment must be discontinued before Day 1
  • Evidence of decompensated liver disease including, but not limited to, a history or presence of clinical ascites, bleeding varices, or hepatic encephalopathy
  • Diabetic and/or hypertensive with clinically significant ocular examination findings
  • History of stroke or transient ischemic attack
  • Immunologically mediated disease (e.g., inflammatory bowel disease [Crohn's disease, ulcerative colitis], celiac disease, rheumatoid arthritis, idiopathic thrombocytopenic purpura, systemic lupus erythematosus, autoimmune hemolytic anemia, scleroderma, sarcoidosis, severe psoriasis requiring oral or injected treatment, or symptomatic thyroid disorder)
  • Chronic pulmonary disease (e.g., chronic obstructive pulmonary disease, interstitial lung disease, pulmonary fibrosis, sarcoidosis)
  • Current or history of any clinically significant cardiac abnormalities/dysfunction
  • Any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids during the course of the trial
  • Myelodysplastic syndromes
  • Organ transplants (including hematopoietic stem cell transplants) other than cornea and hair
  • Pregnant or nursing, or intending to become pregnant during the trial period

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
HBeAg(+) PEG-IntronPEG-Intron™HBeAg-positive participants receive 1.5 mcg/kg/wk PEG-Intron subcutaneously (SC) once weekly for 48 weeks.
HBeAg(-) PEG-IntronPEG-Intron™HBeAg-negative participants receive 1.5 mcg/kg/wk PEG-Intron SC once weekly for 48 weeks.
HBeAg(+) PEGASYSPEGASYS™HBeAg-positive participants receive 180 mcg/kg/wk PEGASYS SC once weekly for 48 weeks.
HBeAG(-) PEGASYSPEGASYS™HBeAg-negative participants receive 180 mcg/kg/wk PEGASYS SC once weekly for 48 weeks.
Primary Outcome Measures
NameTimeMethod
Percentage of HBeAg(+) Participants Achieving HBeAg Seroconversion at 24 Weeks Post-treatmentFU Week 24 (Study Week 72)

Blood samples were drawn to assess the participant's seroconversion status at Follow-up (FU) Week 24. HBeAg seroconversion was defined as loss of HBeAg in HBeAg(+) participants and development of antibody to HBeAg.

Percentage of HBeAg(-) Participants Achieving Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels <2000 IU/mL at 24 Weeks Post-treatmentFU Week 24 (Study Week 72)

The Roche COBAS TaqMan HBV-(High Pure System Assay) was used to measure HBV DNA in blood samples of HBeAg(-) participants. The percentage of HBeAg(-) participants with HBV DNA \<2000 IU/mL at 24 weeks post-treatment was reported.

Secondary Outcome Measures
NameTimeMethod
Percentage of HBeAg(+) Participants Achieving the Combined Response of HBeAg Seroconversion and HBV DNA <2000 IU/mL at 24 Weeks Post-treatmentFU Week 24 (Study Week 72)

HBeAg seroconversion was defined as loss of HBeAg in HBeAg(+) participants and development of antibody to HBeAg. HBV DNA levels in blood were measured by the Roche COBAS TaqMan HBV-(High Pure System Assay). The percentage of HBeAg(+) participants with the combined response of achieving both HBeAg conversion and HBV DNA levels \<2000 IU/mL at 24 weeks post-treatment was reported.

Percentage of HBeAg(+) Participants Achieving HBV DNA <2000 IU/mL at 24 Weeks Post-treatmentFU Week 24 (Study Week 72)

The Roche COBAS TaqMan HBV-(High Pure System Assay) was used to measure HBV DNA in blood samples of HBeAg(+)participants. The percentage of HBeAg(+) participants with HBV DNA \<2000 IU/mL at 24 weeks post-treatment was reported.

Percentage of HBeAg(+) and HBeAg(-) Participants Achieving Alanine Aminotransferase (ALT) Normalization at 24 Weeks Post-treatmentFU Week 24 (Study Week 72)

ALT normalization is a desired goal of HBV treatment, which is defined as having abnormal ALT levels at baseline and subsequently normal ALT levels after receiving treatment, where normal is defined as ≤ 1x the upper limit of normal (ULN). The percentage of HBeAg(+) and HBeAg(-) participants achieving ALT normalization at 24 weeks post-treatment was reported.

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