Clinical trial NCT01438424: Safety and Antiviral Activity of Entecavir in Participants With Chronic Hepatitis B Following Monotherapy in Other Entecavir Trials
Official title: A Preliminary Assessment of Safety and Antiviral Activity of Open-label Entecavir in Subjects With Chronic Hepatitis B Following Monotherapy in Other Entecavir Trials
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis B Virus
HBV
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2011-09-22
Enrollment: 1053
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to provide entecavir to participants who have completed another entecavir trial without achieving virologic response or who relapsed during postdosing follow-up.


Eligibility criteria: Key inclusion criteria:

* Age of 16 years and older
* Receipt of entecavir or lamivudine in a previous entecavir study.

Participants who were, based on their response to entecavir:

* Virologic nonresponders at Week 48
* Partial virologic responders who became nonresponders during the second year of treatment
* Partial virologic responders at Week 96
* Complete responders who relapsed during postdosing follow-up

  * Decompensated liver disease in AI463-048 that met 1 or more of the following criteria:
* Nonresponse to adefovir after at least 24 weeks of treatment
* Partial response to adefovir after 96 weeks of treatment
* Complete response to adefovir after relapsing during postdosing follow-up
* Demonstrated intolerance to adefovir

  * Except for those participants enrolled from AI463-048, compensated liver disease.

Key exclusion criteria:

* HIV coinfection
* Receiving nephrotoxic or hepatotoxic agents
* Ongoing opportunistic infections
* Hemoglobin level \<11.0 g/dL except for those enrolled from AI463-048
* Platelet count \<70,000 mm\^3 except for those enrolled from AI463-048
* Absolute granulocyte count \<1,500 cells/mm\^3
* Recent history of pancreatitis (within 24 weeks prior to first dose of therapy)
* Current evidence of ascites requiring paracentesis, hepatic encephalopathy, or variceal bleeding, except for those enrolled from AI463-048
* Known history of allergy to nucleoside analogues.

Primary outcomes:
measure: Overall Study: Number of Participants With Death As Outcome, Any Adverse Event (AE), Grade 3-4 AEs, Serious Adverse Events (SAEs), and Discontinuations Due to AEs
timeFrame: Continuously from Day 1 through Week 240
measure: Overall Study: Number of Participants With Normal Hematology Values at Baseline and Abnormalities in Hematology Laboratory Test Results Through Week 240
timeFrame: Day 1 of treatment through Week 240
measure: Overall Study: Number of Participants With Normal Pancreatic Enzyme and Renal Function Values at Baseline and Abnormalities in Pancreatic Enzyme and Renal Function Laboratory Test Results at End of Dosing
timeFrame: Day 1 of treatment through Week 240
measure: Overall Study: Number of Participants With Normal Electrolyte and Fasting Glucose Values at Baseline and Abnormalities in Electrolyte and Fasting Glucose Laboratory Test Results at End of Dosing
timeFrame: Day 1 of treatment through Week 240
measure: Week 144: Number of Participants With Death As Outcome, Any AE, Grade 3-4 AEs, SAEs, Discontinuations Due to AEs, and Abnormalities in Selected Laboratory Test Results
timeFrame: Continuously from Day 1 through Week 144
measure: Week 192: Number of Participants With Death As Outcome, Any AE, Grade 3-4 AEs, SAEs, Discontinuations Due to AEs, and Abnormalities in Selected Laboratory Test Results
timeFrame: Continuously from Day 1 through Week 192
measure: Off-treatment Follow-up: Percentage of Participants With Sustained Hepatitis B Virus (HBV) DNA <10,000 Copies by Polymerase Chain Reaction (PCR) Assay (Amendment 11 Cohort)
timeFrame: End of dosing to Week 48 off-treatment follow-up
Secondary outcomes:
measure: Overall Study: Percentage of Participants With Sustained HBV DNA Level <300 Copies/mL by PCR Assay
timeFrame: Study entry to Week 192
measure: Overall Study: Percentage of Participants With Sustained HBV DNA <10^4 Copies/mL by PCR Assay
timeFrame: Study entry to Week 192
measure: Overall Study: Percentage of Participants by HBV DNA Category by PCR Assay
timeFrame: Baseline to Week 192
measure: Overall Study: Mean HBV DNA Level by PCR Assay
timeFrame: Study entry to Week 216
measure: Overall Study: Percentage of Participants Who Achieved a Loss of Hepatitis B e Antigen (HBeAg)
timeFrame: Study entry to Week 216
measure: Overall Study: Percentage of Participants With HBeAg Seroconversion
timeFrame: Study entry to Week 216
measure: Overall Study: Mean Alanine Transaminase (ALT) Levels
timeFrame: Study entry to Week 216
measure: Overall Study: Percentage of Participants Who Achieved ALT Normalization
timeFrame: Study entry to Week 216
measure: Week 192: Percentage of Participants With Histologic Improvement (Efficacy Evaluable Cohort)
timeFrame: Baseline to Week 192
measure: Week 192: Percentage of Participants With Improvement in Fibrosis (Efficacy Evaluable Cohort)
timeFrame: Baseline to Week 192
measure: Overall Study: Percentage of Participants With a Confirmed ≥1 log10 Increase From Nadir in HBV DNA by PCR Assay
timeFrame: Baseline to Week 144
measure: Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay, Loss of HBeAG, Seroconversion, and ALT ≤1.0*Upper Limit of Normal (ULN) (Entecavir Continuous Treatment Cohort)
timeFrame: Baseline to Weeks 48, 96, 144, 192, and 240
measure: Percentage of Participants Who Achieved HBV DNA <300 and <10^4 Copies/mL by PCR Assay and ALT ≤1.0*Upper Limit of Normal (ULN) (Entecavir Retreatment Cohort)
timeFrame: Baseline to Weeks 48, 96, and 144
measure: Week 96: Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay, Loss of HBeAg, HBeAg Seroconversion, and ALT ≤1.0*ULN (Lamivudine Continuous Switch Cohort)
timeFrame: Baseline to Week 96
measure: Week 144: Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay and ALT ≤1.0*ULN (Lamivudine Continuous Switch Cohort)
timeFrame: Baseline to Week 144
measure: Week 96: Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay and ALT ≤1.0*ULN (Lamivudine Retreatment Switch Cohort)
timeFrame: Baseline to Week 96
measure: Week 144: Percentage of Participants Who Achieved HBV DNA <300 Copies/mL by PCR Assay and ALT ≤1.0*ULN (Lamivudine Retreatment Switch Cohort)
timeFrame: Baseline to Week 144
measure: Off-treatment Follow-up: Percentage of Participants With Sustained HBV DNA <1,000, <300, and <10,000 Copies/mL by PCR Assay and With ALT ≤1*ULN (Amendment 11 Cohort)
timeFrame: End of dosing to Weeks 48 and 96 off-treatment follow-up
measure: Off-treatment Follow-up: Mean Change in HBV DNA (Amendment 11 Cohort)
timeFrame: End of dosing to Weeks 48 and 96 off-treatment follow-up
Other outcomes:
Locations:
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Manns MP, Akarca US, Chang TT, Sievert W, Yoon SK, Tsai N, Min A, Pangerl A, Beebe S, Yu M, Wongcharatrawee S. Long-term safety and tolerability of entecavir in patients with chronic hepatitis B in the rollover study ETV-901. Expert Opin Drug Saf. 2012 May;11(3):361-8. doi: 10.1517/14740338.2012.653340. Epub 2012 Jan 11.