Pegylated Interferon(Peg-IFN) in Reducing Relapse Rate in Patients After Discontinuation of NUC Therapy

NCT02594293 | Completed Phase 4

• 1 other identifier: CEASE
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 19

Brief Summary

This study evaluates whether Peg-IFN alfa-2a can reduce the recurrence rate of hepatitis B in 96 weeks after nucleoside analogue (NUC) withdrawal. The HBV HBeAg-Negative patients who received NUC anti-virus treatment for 2.5 years and reached stopping rule in 《Chinese chronic hepatitis B prevention and treatment guidelines》(2010) were randomly assigned into three groups: One group discontinue the NUC treatment and follow up for 96 weeks,One discontinue the NUC treatment ,receive Peg-IFN alfa-2a 180 μg by week for 24 weeks and follow up for 72 weeks,The other discontinue the NUC treatment ,receive Peg-IFN alfa-2a 180 μg by week for 48 weeks and follow up for 48 weeks.

Conditions

Chronic Hepatitis B

Outcome Measures

Primary Outcomes (1)

• Number of participants who relapse

  The total number of relapse (HBV DNA\>2000 IU/ml on 2 separate occasions 1 months apart) during the research period.

  96 weeks

Secondary Outcomes (5)

• Number of participants who relapse

  48 weeks

• Number of participants who achieve HBsAg seroconversion

  At the point of discontinuation of PegIFN therapy

• Number of participants who achieve HBsAg seroconversion

  24,48,72 weeks post-discontinuation of PegIFN therapy

• HBsAg changes from Baseline

  12,24 and 48 weeks

• Predictive value of other markers for recurrence after NUC withdrawal

  48 weeks and 96 weeks

Study Arms (2)

Controlled Group

NO INTERVENTION

Discontinue the NA treatment and follow up for 96 weeks

Pegasys 48 weeks

EXPERIMENTAL

Discontinue the NA treatment ,PegIFN alfa-2a 180 μg by week for 48 weeks and follow up for 48 weeks

Drug: PegIFN alfa-2a

Interventions

PegIFN alfa-2a DRUG

180 μg/ 0.5 ml ,hypodermic injection once a week

Also known as: Pegasys

Pegasys 48 weeks

Eligibility Criteria

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

You may qualify if:

• HBeAg-Negative Chronic Hepatitis B Patients：HBsAg-Positive,HBsAb-Negative,HBeAg-Negative,HBeAb-Positive during screening period and before NA treatment
• NUC monotherapy (including adefovir and entecavir) for more than 2.5 years,and reached stopping rule in 《Chinese chronic hepatitis B prevention and treatment guidelines》(2010):the patients who achieved undetectable HBV DNA (\<300 copies/mL) with normal alanine aminotransferase (ALT) and the consolidation therapy reached 1.5 years ,total course of the treatment reached 2.5 years can stop NUC therapy
• Willing to stop the drug, and signed a written informed consent

You may not qualify if:

• HBsAb positive in screening period
• Compensated or Decompensated liver cirrhosis:with history of cirrhosis before NUC treatment or Child-Pugh score ≥ 5 or Complications of liver cirrhosis such as ascites, hepatic encephalopathy, esophageal gastric varices bleeding
• Hypersensitivity to interferon(IFN) or its active substance, and ineligible to IFN
• A history of immunoregulation drug therapy within one year before entry including IFN and so on.
• Coinfection with HAV、HCV、HDV、HEV 、HIV or with Other chronic liver diseases such as Alcoholic Liver Disease,Inherited Metabolic Liver Disease,Drug induced Liver Disease and nonalcoholic fatty liver
• Autoimmune disease including Autoimmune hepatitis and Psoriasis and so on.
• Hepatocellular carcinoma(HCC) or alpha feto protein(AFP) levels more than 100 ng/ml and Hepatic malignant potential of Imaging examination or AFP levels more than 100 ng/ml for 3 months
• A neutrophil count of less than 1500 per cubic millimeter or a platelet count of less than 90,000 per cubic millimeter
• A serum creatinine level that was more than 1.5 times the upper limit of the normal range
• With other malignant tumors(exclude the cured ones)
• Severe organ dysfunction
• With severe psychiatric condition or nervous disease such as epilepsy, depression, mania, epilepsy, schizophrenia and so on
• Uncontrolled diabetes, hypertension or thyroid disease
• Pregnant women and lactating women or patients with pregnancy plans and not willing to use contraception during the study period
• Participate in other clinical studies at the same time

Sponsors & Collaborators

• Huashan Hospital: lead

Study Sites (19)

Wuhan Seventh People's Hospital

Wuhan, Hubei, China

Location

Changzhou Third People's Hospital

Changzhou, Jiangsu, China

Location

First Affiliated Hospital of Zhejiang University

Hangzhou, Jiangsu, China

Location

People's Hospital of Jiangsu Province

Nanjing, Jiangsu, China

Location

Nantong Third People's Hospital

Nantong, Jiangsu, China

Location

Suzhou Fifth People's Hospital

Suzhou, Jiangsu, China

Location

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, China

Location

Taicang People's Hospital

Taicang, Jiangsu, China

Location

Wuxi Infectious Disease Hospital

Wuxi, Jiangsu, China

Location

Affiliated Hospital of Xuzhou Medical College

Xuzhou, Jiangsu, China

Location

Shandong Provincial Hospital

Jinan, Shandong, China

Location

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, China

Location

Changhai Hospital Affiliated to Second Military Medical University

Shanghai, China

Location

Huashan Hospital Affiliated to Fudan University

Shanghai, China

Location

Ruijin Hospital Affiliate to Shanghai Jiao Tong University School of Medicine

Shanghai, China

Location

Shanghai Public Health Clinical Center

Shanghai, China

Location

Shanghai Third People's Hospital

Shanghai, China

Location

Shuguang Hospital Affiliate to Shanghai University of Traditional Chinese Medicine

Shanghai, China

Location

The Infectious Disease Hospital of Shanghai Huangpu Distric

Shanghai, China

Location

Related Publications (18)

• Ganem D, Prince AM. Hepatitis B virus infection--natural history and clinical consequences. N Engl J Med. 2004 Mar 11;350(11):1118-29. doi: 10.1056/NEJMra031087. No abstract available.

  PMID: 15014185 RESULT

• Liang X, Bi S, Yang W, Wang L, Cui G, Cui F, Zhang Y, Liu J, Gong X, Chen Y, Wang F, Zheng H, Wang F, Guo J, Jia Z, Ma J, Wang H, Luo H, Li L, Jin S, Hadler SC, Wang Y. Epidemiological serosurvey of hepatitis B in China--declining HBV prevalence due to hepatitis B vaccination. Vaccine. 2009 Nov 5;27(47):6550-7. doi: 10.1016/j.vaccine.2009.08.048. Epub 2009 Sep 1.

  PMID: 19729084 RESULT

• Liang X, Bi S, Yang W, Wang L, Cui G, Cui F, Zhang Y, Liu J, Gong X, Chen Y, Wang F, Zheng H, Wang F, Guo J, Jia Z, Ma J, Wang H, Luo H, Li L, Jin S, Hadler SC, Wang Y. Evaluation of the impact of hepatitis B vaccination among children born during 1992-2005 in China. J Infect Dis. 2009 Jul 1;200(1):39-47. doi: 10.1086/599332.

  PMID: 19469708 RESULT

• Lu FM, Zhuang H. Management of hepatitis B in China. Chin Med J (Engl). 2009 Jan 5;122(1):3-4. No abstract available.

  PMID: 19187608 RESULT

• 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 RESULT

• Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology. 2009 Sep;50(3):661-2. doi: 10.1002/hep.23190. No abstract available.

  PMID: 19714720 RESULT

• Liaw YF, Leung N, Kao JH, Piratvisuth T, Gane E, Han KH, Guan R, Lau GK, Locarnini S; Chronic Hepatitis B Guideline Working Party of the Asian-Pacific Association for the Study of the Liver. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2008 update. Hepatol Int. 2008 Sep;2(3):263-83. doi: 10.1007/s12072-008-9080-3. Epub 2008 May 10.

  PMID: 19669255 RESULT

• 中华医学会肝病学分会,中华医学会感染病学分会.慢性乙型肝炎防治指南(2010年版).中华内科杂志,2011;50(2):168-179

  RESULT

• Kim YJ, Kim K, Hwang SH, Kim SS, Lee D, Cheong JY, Cho SW. Durability after discontinuation of nucleos(t)ide therapy in chronic HBeAg negative hepatitis patients. Clin Mol Hepatol. 2013 Sep;19(3):300-4. doi: 10.3350/cmh.2013.19.3.300. Epub 2013 Sep 30.

  PMID: 24133668 RESULT

• Liu F, Wang L, Li XY, Liu YD, Wang JB, Zhang ZH, Wang YZ. Poor durability of lamivudine effectiveness despite stringent cessation criteria: a prospective clinical study in hepatitis B e antigen-negative chronic hepatitis B patients. J Gastroenterol Hepatol. 2011 Mar;26(3):456-60. doi: 10.1111/j.1440-1746.2010.06492.x.

  PMID: 21332542 RESULT

• Seto WK, Hui AJ, Wong VW, Wong GL, Liu KS, Lai CL, Yuen MF, Chan HL. Treatment cessation of entecavir in Asian patients with hepatitis B e antigen negative chronic hepatitis B: a multicentre prospective study. Gut. 2015 Apr;64(4):667-72. doi: 10.1136/gutjnl-2014-307237. Epub 2014 May 15.

  PMID: 24833635 RESULT

• Jeng WJ, Sheen IS, Chen YC, Hsu CW, Chien RN, Chu CM, Liaw YF. Off-therapy durability of response to entecavir therapy in hepatitis B e antigen-negative chronic hepatitis B patients. Hepatology. 2013 Dec;58(6):1888-96. doi: 10.1002/hep.26549. Epub 2013 Oct 17.

  PMID: 23744454 RESULT

• Micco L, Peppa D, Loggi E, Schurich A, Jefferson L, Cursaro C, Panno AM, Bernardi M, Brander C, Bihl F, Andreone P, Maini MK. Differential boosting of innate and adaptive antiviral responses during pegylated-interferon-alpha therapy of chronic hepatitis B. J Hepatol. 2013 Feb;58(2):225-33. doi: 10.1016/j.jhep.2012.09.029. Epub 2012 Oct 6.

  PMID: 23046671 RESULT

• Chen J, Wang Y, Wu XJ, Li J, Hou FQ, Wang GQ. Pegylated interferon alpha-2b up-regulates specific CD8+ T cells in patients with chronic hepatitis B. World J Gastroenterol. 2010 Dec 28;16(48):6145-50. doi: 10.3748/wjg.v16.i48.6145.

  PMID: 21182232 RESULT

• Marcellin P, Bonino F, Yurdaydin C, Hadziyannis S, Moucari R, Kapprell HP, Rothe V, Popescu M, Brunetto MR. Hepatitis B surface antigen levels: association with 5-year response to peginterferon alfa-2a in hepatitis B e-antigen-negative patients. Hepatol Int. 2013 Mar;7(1):88-97. doi: 10.1007/s12072-012-9343-x. Epub 2012 Mar 23.

  PMID: 23518903 RESULT

• Ning Q, Han M, Sun Y, Jiang J, Tan D, Hou J, Tang H, Sheng J, Zhao M. Switching from entecavir to PegIFN alfa-2a in patients with HBeAg-positive chronic hepatitis B: a randomised open-label trial (OSST trial). J Hepatol. 2014 Oct;61(4):777-84. doi: 10.1016/j.jhep.2014.05.044. Epub 2014 Jun 7.

  PMID: 24915612 RESULT

• Ouzan D, Penaranda G, Joly H, Khiri H, Pironti A, Halfon P. Add-on peg-interferon leads to loss of HBsAg in patients with HBeAg-negative chronic hepatitis and HBV DNA fully suppressed by long-term nucleotide analogs. J Clin Virol. 2013 Dec;58(4):713-7. doi: 10.1016/j.jcv.2013.09.020. Epub 2013 Sep 29.

  PMID: 24183313 RESULT

• Li F, Qu L, Liu Y, Wu X, Qi X, Wang J, Zhu H, Yang F, Shen Z, Guo Y, Zhang Y, Yu J, Mao R, Zhang Q, Zhang F, Chen L, Huang Y, Zhang X, Li Q, Zhang W, Zhang J. PegIFN alpha-2a reduces relapse in HBeAg-negative patients after nucleo(s)tide analogue cessation: A randomized-controlled trial. J Hepatol. 2025 Feb;82(2):211-221. doi: 10.1016/j.jhep.2024.07.019. Epub 2024 Jul 31.

  PMID: 39094743 DERIVED

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

peginterferon alfa-2a

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

Study Officials

• Jiming Zhang, M.D.

  Huashan Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: chief physician,professor

Study Record Dates

• First Submitted: October 11, 2015
• First Posted: November 3, 2015
• Study Start: October 1, 2015
• Primary Completion: September 1, 2022
• Study Completion: September 1, 2022
• Last Updated: October 31, 2022

Record last verified: 2022-10

Locations

CN (19)