A Phase III Study of the Safety and Efficacy of Entecavir in Pediatric Patients With Chronic Hepatitis B Virus Infection

NCT01079806 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: AI463-189 ST
• Study Type: interventional
• Target: 180
• Locations: 14 countries
• Sites: 44

Brief Summary

The purpose of this study was to evaluate the safety and efficacy of entecavir in pediatric patients with chronic hepatitis B virus infection

Conditions

Chronic Hepatitis B Virus, Pediatric

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Achieved a Combination of Hepatitis B Virus (HBV) DNA Suppression and Hepatitis B e Antigen (HBeAg) Seroconversion at Week 48

  Suppression=HBV DNA\<50 IU/mL (approximately 300 copies/mL) using the Roche COBAS TaqMan HBV Test for use with the High Pure System assay; seroconversion=undetectable HBeAg and detectable anti-hepatitis B e antibodies. While the analysis of the primary endpoint was based on a randomized sample size of 123 participants (the Primary Cohort), the size of the overall study population was augmented to 180 randomized participants to meet global regulatory requirements.

  At Week 48

Secondary Outcomes (14)

• Percentage of Participants With Hepatitis B Virus (HBV) DNA <50 IU/mL at Week 48

  At Week 48

• Percentage of Participants With Serum Alanine Aminotransferase ≤1*Upper Limit of Normal at Week 48

  At Week 48

• Percentage of Participants With Hepatitis B Virus DNA <Limit of Quantitation (LOQ) at Week 48

  At Week 48

• Percentage of Participants With Hepatitis B e Antigen (HBeAg) Seroconversion at Week 48 (Undetectable HBeAg and Presence of Anti-HBeAb)

  At Week 48

• Percentage of Participants Who Achieved Sustained HBeAg Seroconversion During Off-treatment Follow up Among Participants Who Achieved HBeAg Seroconversion at End of Dosing (EOD).

  Week 48, EOD (2 years)

Study Arms (2)

Entecavir

ACTIVE COMPARATOR

Participants received entecavir, 0.015 mg/kg up to 0.5 mg, once daily, for 96 to 144 weeks, depending on response

Drug: Entecavir

Placebo

PLACEBO COMPARATOR

Participants received placebo, 0 mg, once daily, for 48 to 96 weeks, depending on response

Drug: Placebo

Interventions

Entecavir DRUG

Tablets/oral solution, 0.015 mg/kg up to 0.5 mg, administered orally, once daily, for 96 to144 weeks, depending on response

Also known as: Baraclude, BMS-200475

Entecavir

Placebo DRUG

Tablets/oral solution, 0 mg, administered orally, once daily, for 48 to 96 weeks, depending on response

Placebo

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Males and females, aged 2 to \<18 years
• Hepatitis B surface antigen-positive
• Detectable hepatitis B e (HBe) antigen, and no detectable anti-HBe antibodies
• Alanine aminotransferase (ALT) 1.5 to \<10 times the upper limit of normal at screening and within 8 to 24 weeks prior to screening
• Evidence of the presence of hepatitis B virus DNA at least 4 weeks before screening and \>100,000 copies/mL at screening

You may not qualify if:

• Any prior therapy with entecavir
• At least 12 weeks of prior therapy with any nucleoside or nucleotide antiviral agent
• Therapy with interferon alpha, thymosin alpha, or nucleototide antiviral agents within 24 weeks of screening
• Coinfection with HIV, hepatitis C virus, or hepatitis D virus
• Decompensated liver disease
• Liver transplant recipients
• Other forms of acute and chronic conditions which may cause increased ALT levels
• Children who were breastfed while their mothers received lamivudine or whose mothers received lamivudine during pregnancy

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (44)

University Of California, San Francisco

San Francisco, California, 94143, United States

Location

Connecticut Children'S Medical Center

Hartford, Connecticut, 06106, United States

Location

Children'S National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

University Of Florida

Gainesville, Florida, 32610, United States

Location

Romero, Rene

Atlanta, Georgia, 30322, United States

Location

Indiana University School Of Medicine / Riley Hospital

Indianapolis, Indiana, 46202, United States

Location

Johns Hopkins School Of Medicine

Baltimore, Maryland, 21287, United States

Location

Shah, Uzma

Boston, Massachusetts, 02114, United States

Location

Boston Childrens Hospital

Boston, Massachusetts, 02115, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Levine Children'S Hospital At Carolinas Medical Center

Charlotte, North Carolina, 28203, United States

Location

Children'S Hospital Of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Texas Children'S Hospital

Houston, Texas, 77030, United States

Location

Inova Fairfax Hospital For Children

Fairfax, Virginia, 22031, United States

Location

Local Institution

Bunos Aires, Buenos Aires, 1425, Argentina

Location

Local Institution

Brussels, 1200, Belgium

Location

Local Institution

Toronto, Ontario, M5G 1X8, Canada

Location

Local Institution

Mainz, Rhineland-Palatinate, 55131, Germany

Location

Local Institution

Starnberg, 82319, Germany

Location

Local Institution

Wuppertal, 42283, Germany

Location

Local Institution

Thesaloniki, 54635, Greece

Location

Local Institution

Guwahati, 781006, India

Location

Local Institution

Hyderabad, 500029, India

Location

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Beersheba, 84101, Israel

Location

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Petah Tikva, Israel

Location

Local Institution

Safed, 13110, Israel

Location

Local Institution

Bydgoszcz, 85-030, Poland

Location

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Krakow, 31-202, Poland

Location

Local Institution

Wroclaw, 50-345, Poland

Location

Local Institution

Bucharest, 011743, Romania

Location

Local Institution

Iași, 700309, Romania

Location

Local Institution

Timișoara, 300011, Romania

Location

Local Institution

Moscow, 111123, Russia

Location

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Moscow, 117198, Russia

Location

Local Institution

Novokuznetsk, 654063, Russia

Location

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Saint Petersburg, 197022, Russia

Location

Local Institution

Daegu, 700-721, South Korea

Location

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Seoul, 135-710, South Korea

Location

Local Institution

Seoul, 138-736, South Korea

Location

Local Institution

Tainan, 704, Taiwan

Location

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Taipei, 100, Taiwan

Location

Local Institution

London, Greater London, SE5 9RS, United Kingdom

Location

Local Institution

Birmingham, West Midlands, B4 6NH, United Kingdom

Location

Related Publications (1)

• Jonas MM, Chang MH, Sokal E, Schwarz KB, Kelly D, Kim KM, Ling SC, Rosenthal P, Oraseanu D, Reynolds L, Thiry A, Ackerman P. Randomized, controlled trial of entecavir versus placebo in children with hepatitis B envelope antigen-positive chronic hepatitis B. Hepatology. 2016 Feb;63(2):377-87. doi: 10.1002/hep.28015. Epub 2015 Oct 16.

  PMID: 26223345 DERIVED

Related Links

• BMS clinical trial educational resource
• Investigator Inquiry form

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

entecavir

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

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

Clinical.Trials@bms.com

please email

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 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2010
• First Posted: March 3, 2010
• Study Start: June 30, 2010
• Primary Completion: March 31, 2013
• Study Completion: March 31, 2018
• Last Updated: May 9, 2019
• Results First Posted: April 21, 2014

Record last verified: 2019-04

Locations

BE (1); AR (1); CA (1); DE (3); IL (3); IN (2); US (15); GR (1); RU (4); RO (3); PL (3); TW (2); KR (3); GB (2)