Hepatitis B Virus (HBV) Viral Suppression by Entecavir in Adefovir Partial Responders - Full Text View

Sponsor:	Pacific Health Foundation
Collaborator:	Bristol-Myers Squibb
Information provided by:	Pacific Health Foundation
ClinicalTrials.gov Identifier:	NCT00704106

Purpose

We propose a largely retrospective study with short-term prospective follow-up in a subgroup of patients who have not yet been treated with 48 weeks of entecavir following partial response to adefovir. The aim of the study is to describe sequential virologic response to adefovir and entecavir.

Condition	Intervention
Hepatitis B	Drug: Entecavir

Study Type:	Observational
Study Design:	Cohort
Official Title:	HBV Viral Suppression by Entecavir in Adefovir Partial Responders

Resource links provided by NLM:

MedlinePlus related topics: Hepatitis Hepatitis B

Drug Information available for: Adefovir Entecavir

U.S. FDA Resources

Further study details as provided by Pacific Health Foundation:

Primary Outcome Measures:

HBV DNA PCR after 12 weeks of entecavir from the time of medication switching: percent of patients with <2log drop in HBV DNA and percent of patients with complete viral suppression during adefovir versus during entecavir. [ Time Frame: 48 weeks or after ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

HBV DNA PCR after 24 weeks of entecavir from the time of medication switching. [ Time Frame: 48 weeks or after ] [ Designated as safety issue: No ]
HBV DNA PCR after 48 weeks of entecavir from the time of medication switching. [ Time Frame: 48 weeks or after ] [ Designated as safety issue: No ]
BR and CR at 24 and 48 weeks of therapy with entecavir. [ Time Frame: 48 weeks or after. ] [ Designated as safety issue: No ]
BR and CR for longer duration of therapy if available. [ Time Frame: 48 weeks or after. ] [ Designated as safety issue: No ]

Biospecimen Retention: None Retained

Biospecimen Description:

Estimated Enrollment:	120
Study Start Date:	May 2008
Estimated Study Completion Date:	March 2012

Groups/Cohorts	Assigned Interventions
Group 1 Persistent viremia after 48 weeks or longer.	Drug: Entecavir 0.5 or 1 mg dose qd
Group 2 <2 log IU/mL drop from initial HBVDNA after 12 weeks of adefovir	Drug: Entecavir 0.5 or 1 mg dose qd
Group 3 Patients who responded to adefovir and were switched to entecavir.	Drug: Entecavir 0.5 or 1 mg dose qd
Group 4 Patients with 160 copies/mL (100 IU/mL) or higher at the time of medication switch.	Drug: Entecavir 0.5 or 1 mg dose qd

Detailed Description:

Amendment was made, and approved by WIRB in January 2009, to this protocol: We propose a largely retrospective study with short-term prospective follow-up in a subgroup of patients who have not yet been treated with 96 weeks of entecavir following adefovir treatment. The aim of the study is to describe sequential virologic response to adefovir and entecavir.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

Age 18 years or older
All genders and ethnicity
Positive HBsAg
HBeAg positive and negative
Pretreatment HBV DNA of 10,000 copies/mL or higher (for purposes of this study, both copies and equivalent IU measurements will be recorded and analyzed)
Patients who are switched to, or prescribed, entecavir after treatment with adefovir for at least 12 weeks by the providing physician
Patients with and without prior lamivudine exposure will be enrolled but enrollment of lamivudine experienced cases will be limited to no more than 30 patients total

Criteria

KEY INCLUSION CRITERIA:

Age 18 years or older
All genders and ethnicity
Positive HBsAg
HBeAg positive and negative
Pretreatment HBV DNA of 10,000 copies/mL or higher (for purposes of this study, both copies and equivalent IU measurements will be recorded and analyzed)
Patients who are switched to, or prescribed, entecavir after treatment with adefovir for at least 12 weeks by the providing physician.
Patients with and without prior lamivudine exposure will be enrolled but enrollment of lamivudine experienced cases will be limited to no more than 30 patients total

KEY EXCLUSION CRITERIA:

Patients who refused to consent to the study
Patients younger than 18
Vulnerable subjects such as pregnant women, prisoners, employees, patients with significant cognitive deficits.
Patients with prior exposure to another nucleoside for more than 2 weeks. Those with prior exposure to lamivudine will be enrolled under conditions detailed above.
HIV co-infection
HCV co-infection
HDV co-infection
Recipients of solid organ transplantation
Patients who receive high-dose steroid (60 mg/d or higher and for longer than 10 days)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00704106

Contacts

Contact: Nghia H Nguyen, B.A.	408-995-0333	nghianguyen214@gmail.com
Contact: Long H Nguyen, B.A.	408-995-0333	longnguyen07@gmail.com

Locations

United States, California
San Jose Gastroenterology	Recruiting
San Jose, California, United States, 95116
Contact: Nghia H Nguyen, B.A. 408-995-0333 nghianguyen214@gmail.com
Principal Investigator: Huy N Trinh, M.D.
San Jose Gastroenterology	Recruiting
San Jose, California, United States, 95128
Contact: Nghia H Nguyen, B.A. 408-995-0333 nghianguyen214@gmail.com
Principal Investigator: Huy N Trinh, M.D.
United States, Illinois
Asian Village Medical Clinic	Recruiting
Chicago, Illinois, United States, 60640
Contact: Phuong Tran, M.D. 773-275-4250 lptran@comcast.net
Principal Investigator: Phuong Tran, M.D.
United States, Texas
Digestive Health Associates of Texas	Recruiting
Plano, Texas, United States, 75093
Contact: Son Do, M.D. 972-398-0393 dotuongson@yahoo.com
Principal Investigator: Son Do, M.D.
Houston Gastroenterology Clinic	Recruiting
Houston, Texas, United States, 77072
Contact: Thuan Nguyen, M.D. 281-983-0938 giassoc@ev1.net
Principal Investigator: Thuan Nguyen, M.D.

Sponsors and Collaborators

Pacific Health Foundation

Bristol-Myers Squibb

Investigators

Principal Investigator:	Huy N Trinh, M.D.	Pacific Health Foundation
Principal Investigator:	Mindie H Nguyen, M.D., M.A.S.	Pacific Health Foundation

More Information

Publications:

McMahon BJ. Epidemiology and natural history of hepatitis B. Semin Liver Dis. 2005;25 Suppl 1:3-8. Review.

Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, Huang GT, Iloeje UH; REVEAL-HBV Study Group. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006 Jan 4;295(1):65-73.

Iloeje UH, Yang HI, Su J, Jen CL, You SL, Chen CJ; Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-In HBV (the REVEAL-HBV) Study Group. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology. 2006 Mar;130(3):678-86.

Liaw YF, Sung JJ, Chow WC, Farrell G, Lee CZ, Yuen H, Tanwandee T, Tao QM, Shue K, Keene ON, Dixon JS, Gray DF, Sabbat J; Cirrhosis Asian Lamivudine Multicentre Study Group. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med. 2004 Oct 7;351(15):1521-31.

Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology. 2007 Feb;45(2):507-39. No abstract available. Erratum in: Hepatology. 2007 Jun;45(6):1347.

Keeffe EB, Dieterich DT, Han SH, Jacobson IM, Martin P, Schiff ER, Tobias H, Wright TL. A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: an update. Clin Gastroenterol Hepatol. 2006 Aug;4(8):936-62. Epub 2006 Jul 14. Review.

Shaw T, Locarnini S. Entecavir for the treatment of chronic hepatitis B. Expert Rev Anti Infect Ther. 2004 Dec;2(6):853-71. Review.

Chan HL, Heathcote EJ, Marcellin P, Lai CL, Cho M, Moon YM, Chao YC, Myers RP, Minuk GY, Jeffers L, Sievert W, Bzowej N, Harb G, Kaiser R, Qiao XJ, Brown NA; 018 Study Group. Treatment of hepatitis B e antigen positive chronic hepatitis with telbivudine or adefovir: a randomized trial. Ann Intern Med. 2007 Dec 4;147(11):745-54. Epub 2007 Oct 1.

Keeffe EB, Zeuzem S, Koff RS, Dieterich DT, Esteban-Mur R, Gane EJ, Jacobson IM, Lim SG, Naoumov N, Marcellin P, Piratvisuth T, Zoulim F. Report of an international workshop: Roadmap for management of patients receiving oral therapy for chronic hepatitis B. Clin Gastroenterol Hepatol. 2007 Aug;5(8):890-7. Epub 2007 Jul 13. Review.

Colonno RJ, Rose R, Baldick CJ, Levine S, Pokornowski K, Yu CF, Walsh A, Fang J, Hsu M, Mazzucco C, Eggers B, Zhang S, Plym M, Klesczewski K, Tenney DJ. Entecavir resistance is rare in nucleoside naïve patients with hepatitis B. Hepatology. 2006 Dec;44(6):1656-65.

Tenney DJ, Rose RE, Baldick CJ, Pokornowski KA, Eggers BJ, Fang J, Wichroski MJ, Xu D, Yang J, Wilber RB, Colonno RJ. Long-term monitoring shows hepatitis B virus resistance to entecavir in nucleoside-naïve patients is rare through 5 years of therapy. Hepatology. 2009 May;49(5):1503-14.

Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, Chang TT, Kitis G, Rizzetto M, Marcellin P, Lim SG, Goodman Z, Ma J, Arterburn S, Xiong S, Currie G, Brosgart CL; Adefovir Dipivoxil 438 Study Group. Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B. N Engl J Med. 2005 Jun 30;352(26):2673-81.

Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, Chang TT, Kitis G, Rizzetto M, Marcellin P, Lim SG, Goodman Z, Ma J, Brosgart CL, Borroto-Esoda K, Arterburn S, Chuck SL; Adefovir Dipivoxil 438 Study Group. Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B for up to 5 years. Gastroenterology. 2006 Dec;131(6):1743-51. Epub 2006 Sep 20.

Ha NB, Ha NB, Garcia RT, Trinh HN, Vu AA, Nguyen HA, Nguyen KK, Levitt BS, Nguyen MH. Renal dysfunction in chronic hepatitis B patients treated with adefovir dipivoxil. Hepatology. 2009 Sep;50(3):727-34.

Responsible Party:	Pacific Health Foundation ( Huy N. Trinh/Mindie H. Nguyen )
Study ID Numbers:	PHF008
Study First Received:	June 20, 2008
Last Updated:	November 23, 2009
ClinicalTrials.gov Identifier:	NCT00704106 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Pacific Health Foundation:

Hepatitis B
HBV
Treatment

Additional relevant MeSH terms:

Anti-Infective Agents
Liver Diseases
Hepatitis, Viral, Human
Hepadnaviridae Infections
Antiviral Agents
Pharmacologic Actions
Hepatitis

Virus Diseases
Digestive System Diseases
Entecavir
Therapeutic Uses
Hepatitis B
DNA Virus Infections

ClinicalTrials.gov processed this record on November 27, 2009