Safety and Antiviral Activity of Entecavir in Participants With Chronic Hepatitis B Following Monotherapy in Other Entecavir Trials

NCT01438424 | Completed Phase 2 Results

• 1 other identifier: AI463-901
• Study Type: interventional
• Target: 1,053
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Hepatitis B Virus; HBV

Outcome Measures

Primary Outcomes (7)

• 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

  An AE is a new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not be causally related to treatment. An SAE is an unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening or disabling. ALT=alanine transaminase; ULN=upper limit of normal.

  Continuously from Day 1 through Week 240

• Overall Study: Number of Participants With Normal Hematology Values at Baseline and Abnormalities in Hematology Laboratory Test Results Through Week 240

  Hemoglobin (g/dL): Grade (Gr) 1=9.5-11.0; Gr 2=8.0-\<9.5; Gr 3=6.5-\<8.0; Gr 4=\<6.5 White blood cells (cells/mm\^3): Gr 1=2,500-\<4,000; Gr 2=1,000-\<2,500; Gr 3=800-\<1,000; Gr 4=\<800. Neutrophils (cells/mm\^3): Gr 1=1000-\<1500; Gr 2=750-\<1000; Gr 3=500-\<750; Gr 4=\<500. Platelets (cells/mm\^3): Gr 1=75,000-99,000; Gr 2=50,000-\<75,000; Gr 3=20,000-\<50,000; Gr 4=\<20,000. Prothrombin time (seconds): Gr 1=1.01-\<1.26\*ULN; Gr 2=1.26-\<1.51 \*ULN; Gr 3=1.51-3\*ULN; Gr 4=\>3\*ULN. INR: Gr 1=1.24-1.5; Gr 2=1.5-2; Gr 3=2-3; Gr 4=\>3. INR=international normalized ratio; ULN=upper limit of normal. .

  Day 1 of treatment through Week 240

• 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

  Amylase: Grade 1=1.10-\<1.40\*ULN; Grade 2=1.40-\< 2.10\*ULN; Grade 3=2.10-5.00\*ULN; Grade 4=\>5.00\*ULN. Lipase: Grade 1.1-\<1.4\*ULN; Grade 2=1.4-\<2.1\*ULN; Grade 3=2.1-5.0\*ULN; Grade 4=\>5.0\*ULN. Creatinine: Grade 1=1.10-\< 1.60\*ULN; Grade 2=1.60-\<3.10\*ULN; Grade 3=3.10-6.00\*ULN; Grade 4=\>6.00\*ULN. Blood urea nitrogen (BUN): Grade 1=1.25-\<2.60\*ULN; Grade 2=2.60-\<5.10\*ULN; Grade 3=5.10-10\*ULN; Grade 4=\>10\*ULN. ULN=upper limit of normal.

  Day 1 of treatment through Week 240

• 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

  Hypochloremia: Grade (Gr) 1=90-93; Gr 2=85-\<90; Gr 3=80-\<85; Gr 4=40-\<80. Hyperchloremia: Gr 1=113-\<117; Gr 2=117-\<121; Gr 3=121-125; Gr 4\>125. Hypocarbia: Gr 1=19-21; Gr 2=15-\<19; Gr 3=41-45; Gr 4=\>45. Hypercarbia: Gr 1=31-36; Gr 2=37-40; Gr 3=41-45; Gr 4=\>45. Hyponatremia: Gr 1=130-132; Gr 2=123-\<130; Gr 3=116-\<123; Gr 4\<116. Hypernatremia: Gr 1=148-\<151; Gr 2=151-\<158; Gr 3=158-165; Gr 4=\>165. Hypokalemia: Gr 1=3-3.4; Gr 2=2.5-\<3; Gr 3=2-\<2.5; Gr 4=\<2. Hyperkalemia: Gr 1=5.6-\<6.1; G2=6.1-\<6.6; Gr 3=6.6-7; Gr 4=\>7. Hypoglycemia: Gr 1=55-64; Gr 2=40-\<55; Gr 3=30-\< 40; G4=-\<30. Hyperglycemia: Gr 1=116-\<161; Gr 2=161-\<251; Gr 3=251-500; Gr 4\>500.

  Day 1 of treatment through Week 240

• 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

  An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. An SAE is any unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening or disabling. AST=aspartate aminotransferase; ULN=upper limit of normal.

  Continuously from Day 1 through Week 144

• 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

  An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. An SAE is any unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. CTC Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening or disabling. ALT=alanine aminotransferase; ULN=upper limit of normal.

  Continuously from Day 1 through Week 192

• 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)

  The Amendment 11 Cohort consisted of participants who were hepatitis B e antigen (HBeAg) negative and who had compensated liver disease, a minimum of 192 weeks (4 years) of treatment with entecavir, HBV DNA \<300 copies/mL by PCR assay for ≥48 weeks before end of dosing and on the last observed result ≤24 weeks prior to end of dosing, and serum ALT levels ≤1.0\*ULN at the end of study drug dosing.ALT=alanine aminotransferase; ULN=upper limit of normal.

  End of dosing to Week 48 off-treatment follow-up

Secondary Outcomes (19)

• Overall Study: Percentage of Participants With Sustained HBV DNA Level <300 Copies/mL by PCR Assay

  Study entry to Week 192

• Overall Study: Percentage of Participants With Sustained HBV DNA <10^4 Copies/mL by PCR Assay

  Study entry to Week 192

• Overall Study: Percentage of Participants by HBV DNA Category by PCR Assay

  Baseline to Week 192

• Overall Study: Mean HBV DNA Level by PCR Assay

  Study entry to Week 216

• Overall Study: Percentage of Participants Who Achieved a Loss of Hepatitis B e Antigen (HBeAg)

  Study entry to Week 216

Study Arms (1)

Entecavir, 1.0 mg, with or without lamivudine

EXPERIMENTAL

Drug: Entecavir; Drug: Lamivudine

Interventions

Entecavir DRUG

Tablets, Oral, 1.0 mg, once daily

Also known as: Baraclude

Entecavir, 1.0 mg, with or without lamivudine

Lamivudine DRUG

Oral, 100 mg, daily

Entecavir, 1.0 mg, with or without lamivudine

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Related Publications (1)

• 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.

  PMID: 22233350 DERIVED

MeSH Terms

Conditions

Hepatitis B

Interventions

entecavir; Lamivudine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides

Results Point of Contact

• Title: BMS Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2011
• First Posted: September 22, 2011
• Study Start: January 1, 2001
• Primary Completion: December 1, 2009
• Study Completion: April 1, 2011
• Last Updated: August 23, 2012
• Results First Posted: August 23, 2012

Record last verified: 2012-07