An Open-label Trial of 48-week Peginterferon Alfa-2a (PEGASYS) to Assess the Sustained Response of Chronic Hepatitis B Patients With HBeAg Seroconversion on Nucleot(s)Ide Analogue Therapy

NCT02068365 | Completed Phase 4

• 1 other identifier: ML28486
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multi-center, single-arm, open-label study on the virological response of chronic HBV infection to pegyinterferon-alfa-2a among patients who achieved HBeAg seroconversion on nucleos(t)ide analogue (NA) treatment. The primary endpoint of this study is to investigate the sustained response (HBeAg seroconversion with HBV DNA \<2000 IU/ml) to peginterferon at 24 weeks after the end of treatment.

Conditions

Chronic Hepaititis B

Outcome Measures

Primary Outcomes (1)

• Sustained response (HBeAg seroconversion and HBV DNA <2000 IU/ml)

  24 weeks post-treatment

Secondary Outcomes (5)

• HBeAg loss and seroconversion

  24 weeks post-treatment and follow up for 5 years.

• HBsAg loss and seroconversion

  24 weeks post-treatment and follow up for 5 years.

• HBV DNA <2000IU/ml and undetectable

  24 weeks post-treatment and follow up for 5 years.

• ALT normalization

  24 weeks post-treatment and long-term follow-up

• Sustained response

  5 years post treatment

Study Arms (1)

Pegyinterferon-alfa-2a

OTHER

Pegyinterferon-alfa-2a 180mcq weekly for 48 weeks

Drug: Pegyinterferon-alfa-2a

Interventions

Pegyinterferon-alfa-2a DRUG

Pegyinterferon-alfa-2a 180mcq weekly for 48 weeks

Pegyinterferon-alfa-2a

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male \& female patients \>= 18 and \< 70 years of age
• Positive HBeAg before starting NA treatment
• Treated by a single NA (lamivudine, adefovir, entecavir or tenofovir) for 6 months to 5 years
• Developed HBeAg seroconversion (HBeAg negative and ant-HBe negative) with undetectable HBV DNA by PCR based assay on NA treatment.
• Negative urine or serum pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of test drug. Additionally, all females must be using reliable contraception during the study and for 3 months after treatment completion

You may not qualify if:

• Evidence of decompensated liver disease (Childs B-C), hepato-cellular carcinoma, pre-existing severe depression or other psychiatric disease, significant cardiac disease, significant renal disease, seizure disorders or severe retinopathy.
• received telbivudine as the antiviral therapy or have received more than one NA in the past.
• received interferon or peginterferon treatment in the past.
• received antiviral therapy for any systemic anti-viral, anti-neoplastic or immuno-modulatory treatment (including supraphysiologic doses of steroids and radiation) within the past 6 months.
• Positive test at screening for anti-HIV, anti-HCV.
• Patients who are expected to need systemic antiviral therapy other than that provided by the study at any time during their participation in the study are also excluded. Exception: patients who have had a limited (\<=7 days) course of acyclovir for herpetic lesions more than 1 month prior to the first administration of test drug are not excluded.
• Serum total bilirubin \> 3 times the upper limit of normal at screening.
• History or other evidence of bleeding from esophageal varices or other conditions consistent with decompensated liver disease.
• History or other evidence of a medical condition associated with chronic liver disease other than HBV (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver diseases including Wilson's and alpha1-antitrypsin deficiency, alcoholic liver disease, toxin exposures, thalassemia).
• Women with ongoing pregnancy or who are breast feeding.
• Neutrophil count \<1500 cells/mm3 or platelet count \<90,000 cells/mm3 at screening.
• Hemoglobin \< 11.5 g/dL for females and \< 12.5 g/dL for men at screening.
• Serum creatinine level \>120 umol/ml for men and \>105 umol/ml for women at screening.
• History of severe psychiatric disease, especially depression. Severe psychiatric disease is defined as major depression or psychosis, a period of treatment with an antidepressant medication or major tranquilizer at therapeutic doses for depression or psychosis for at least 3 months, a suicidal attempt, hospitalization for psychiatric disease, or a period of disability due to a psychiatric disease.
• History of immunologically mediated disease (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis).

Sponsors & Collaborators

• Chinese University of Hong Kong: lead

Study Sites (1)

Prince of Wales Hospital

Shatin, Hong Kong

Location

Related Publications (10)

• Sung JJ, Tsoi KK, Wong VW, Li KC, Chan HL. Meta-analysis: Treatment of hepatitis B infection reduces risk of hepatocellular carcinoma. Aliment Pharmacol Ther. 2008 Nov 1;28(9):1067-77. doi: 10.1111/j.1365-2036.2008.03816.x. Epub 2008 Jul 24.

  PMID: 18657133 BACKGROUND

• European Association For The Study Of The Liver. EASL clinical practice guidelines: Management of chronic hepatitis B virus infection. J Hepatol. 2012 Jul;57(1):167-85. doi: 10.1016/j.jhep.2012.02.010. Epub 2012 Mar 20. No abstract available.

  PMID: 22436845 BACKGROUND

• Fung J, Lai CL, Tanaka Y, Mizokami M, Yuen J, Wong DK, Yuen MF. The duration of lamivudine therapy for chronic hepatitis B: cessation vs. continuation of treatment after HBeAg seroconversion. Am J Gastroenterol. 2009 Aug;104(8):1940-6; quiz 1947. doi: 10.1038/ajg.2009.200. Epub 2009 May 19.

  PMID: 19455108 BACKGROUND

• Liang Y, Jiang J, Su M, Liu Z, Guo W, Huang X, Xie R, Ge S, Hu J, Jiang Z, Zhu M, Wong VW, Chan HL. Predictors of relapse in chronic hepatitis B after discontinuation of anti-viral therapy. Aliment Pharmacol Ther. 2011 Aug;34(3):344-52. doi: 10.1111/j.1365-2036.2011.04738.x. Epub 2011 Jun 14.

  PMID: 21671967 BACKGROUND

• Wong VW, Wong GL, Yan KK, Chim AM, Chan HY, Tse CH, Choi PC, Chan AW, Sung JJ, Chan HL. Durability of peginterferon alfa-2b treatment at 5 years in patients with hepatitis B e antigen-positive chronic hepatitis B. Hepatology. 2010 Jun;51(6):1945-53. doi: 10.1002/hep.23568.

  PMID: 20209602 BACKGROUND

• Marcellin P, Bonino F, Lau GK, Farci P, Yurdaydin C, Piratvisuth T, Jin R, Gurel S, Lu ZM, Wu J, Popescu M, Hadziyannis S; Peginterferon alfa-2a in HBeAg-negative Chronic Hepatitis B Study Group. Sustained response of hepatitis B e antigen-negative patients 3 years after treatment with peginterferon alpha-2a. Gastroenterology. 2009 Jun;136(7):2169-2179.e1-4. doi: 10.1053/j.gastro.2009.03.006. Epub 2009 Mar 19.

  PMID: 19303414 BACKGROUND

• Song BC, Suh DJ, Lee HC, Chung YH, Lee YS. Hepatitis B e antigen seroconversion after lamivudine therapy is not durable in patients with chronic hepatitis B in Korea. Hepatology. 2000 Oct;32(4 Pt 1):803-6. doi: 10.1053/jhep.2000.16665.

  PMID: 11003626 BACKGROUND

• Dienstag JL, Cianciara J, Karayalcin S, Kowdley KV, Willems B, Plisek S, Woessner M, Gardner S, Schiff E. Durability of serologic response after lamivudine treatment of chronic hepatitis B. Hepatology. 2003 Apr;37(4):748-55. doi: 10.1053/jhep.2003.50117.

  PMID: 12668966 BACKGROUND

• Ryu SH, Chung YH, Choi MH, Kim JA, Shin JW, Jang MK, Park NH, Lee HC, Lee YS, Suh DJ. Long-term additional lamivudine therapy enhances durability of lamivudine-induced HBeAg loss: a prospective study. J Hepatol. 2003 Oct;39(4):614-9. doi: 10.1016/s0168-8278(03)00394-5.

  PMID: 12971973 BACKGROUND

• van Nunen AB, Hansen BE, Suh DJ, Lohr HF, Chemello L, Fontaine H, Heathcote J, Song BC, Janssen HL, de Man RA, Schalm SW. Durability of HBeAg seroconversion following antiviral therapy for chronic hepatitis B: relation to type of therapy and pretreatment serum hepatitis B virus DNA and alanine aminotransferase. Gut. 2003 Mar;52(3):420-4. doi: 10.1136/gut.52.3.420.

  PMID: 12584227 BACKGROUND

Study Officials

• Henry LY Chan, MD

  Chinese University of Hong Kong

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 28, 2014
• First Posted: February 21, 2014
• Study Start: June 1, 2013
• Primary Completion: June 1, 2019
• Study Completion: June 1, 2019
• Last Updated: July 31, 2019

Record last verified: 2019-07

Locations

HK (1)