Clinical trial NCT00704106: Hepatitis B Virus (HBV) Viral Suppression by Entecavir in Adefovir Partial Responders
Official title: HBV Viral Suppression by Entecavir in Adefovir Partial Responders
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hepatitis B
Keywords: Hepatitis B
HBV
Treatment
Lead sponsor: Pacific Health Foundation
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2008-06-24
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
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

Brief summary: 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.

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 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)

Primary outcomes:
measure: 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.
timeFrame: 48 weeks or after
Secondary outcomes:
measure: HBV DNA PCR after 24 weeks of entecavir from the time of medication switching.
timeFrame: 48 weeks or after
measure: HBV DNA PCR after 48 weeks of entecavir from the time of medication switching.
timeFrame: 48 weeks or after
measure: BR and CR at 24 and 48 weeks of therapy with entecavir.
timeFrame: 48 weeks or after.
measure: BR and CR for longer duration of therapy if available.
timeFrame: 48 weeks or after.
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
city: San Jose
country: United States
facility: San Jose Gastroenterology
state: California
city: San Jose
country: United States
facility: San Jose Gastroenterology
state: California
city: Chicago
country: United States
facility: Asian Village Medical Clinic
state: Illinois
city: Houston
country: United States
facility: Houston Gastroenterology Clinic
state: Texas
city: Plano
country: United States
facility: Digestive Health Associates of Texas
state: Texas
Study officials:
affiliation: Pacific Health Foundation
name: Huy N Trinh, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Pacific Health Foundation
name: Mindie H Nguyen, M.D., M.A.S.
role: PRINCIPAL_INVESTIGATOR
References:
citation: McMahon BJ. Epidemiology and natural history of hepatitis B. Semin Liver Dis. 2005;25 Suppl 1:3-8. doi: 10.1055/s-2005-915644.
citation: 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. doi: 10.1001/jama.295.1.65.
citation: 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. doi: 10.1053/j.gastro.2005.11.016.
citation: 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. doi: 10.1056/NEJMoa033364.
citation: Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology. 2007 Feb;45(2):507-39. doi: 10.1002/hep.21513. No abstract available.
citation: 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. doi: 10.1016/j.cgh.2006.05.016. Epub 2006 Jul 14.
citation: Shaw T, Locarnini S. Entecavir for the treatment of chronic hepatitis B. Expert Rev Anti Infect Ther. 2004 Dec;2(6):853-71. doi: 10.1586/14789072.2.6.853.
citation: 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. doi: 10.7326/0003-4819-147-11-200712040-00183. Epub 2007 Oct 1.
citation: 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. doi: 10.1016/j.cgh.2007.05.004. Epub 2007 Jul 13.
citation: 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 naive patients with hepatitis B. Hepatology. 2006 Dec;44(6):1656-65. doi: 10.1002/hep.21422.
citation: 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-naive patients is rare through 5 years of therapy. Hepatology. 2009 May;49(5):1503-14. doi: 10.1002/hep.22841.
citation: 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. doi: 10.1056/NEJMoa042957.
citation: 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. doi: 10.1053/j.gastro.2006.09.020. Epub 2006 Sep 20.
citation: 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. doi: 10.1002/hep.23044.
citation: Nguyen NH, Trinh HN, Nguyen TT, Do ST, Tran P, Nguyen HA, Nguyen KK, Garcia RT, Lutchman GA, Nguyen MH. Safety and efficacy of entecavir in adefovir-experienced patients. J Gastroenterol Hepatol. 2015 Jan;30(1):43-50. doi: 10.1111/jgh.12728.