A Study to Evaluate Addition of Peginterferon Alfa-2a to Chronic Hepatitis B (CHB) Patients Treated With NAs

NCT02894918 | Unknown Phase 4

• 1 other identifier: COMBINE
• Study Type: interventional
• Target: 114
• Locations: 1 country
• Sites: 5

Brief Summary

This study evaluates whether addition of Peginterferon alfa-2a to CHB Patients Treated with nucleoside analogues (NAs) can enhance the rate of HBsAg clearance at end of treatment. This study is a Randomized, open-label, multi-center study. The CHB patients with NAs treatment and have achieved HBV DNA \<15 IU/ml、HBeAg \<100 PEIU/ml、HBsAg positive and HBsAg\<1500 IU/ml will be randomized into 2 groups: Group 1 (Combination group): Maintain NAs treatment while add 48-week standard treatment by Peginterferon alfa 2a 180µg/week Group 2 (Mono NA group) : Maintain NAs treatment for 49 weeks. Note: NAs including: LAM, ADV, ETV, or TDF.

Conditions

Chronic Hepatitis B

Outcome Measures

Primary Outcomes (1)

• The rate of HBsAg loss

  To determine the response rate will be evaluated by HBsAg loss defined as HBsAg level lower than 0.05 IU/ml after 48 week treatment, compared with control group.

  48 weeks

Secondary Outcomes (6)

• Decline of HBeAg quantification

  12 weeks, 24 weeks, 48 weeks of treatment

• Decline of HBsAg quantification

  12 weeks, 24 weeks, 48 weeks of treatment

• The rate of HBeAg loss

  48 weeks

• The rate of HBeAg seroconversion

  48 weeks

• The rate of HBsAg seroconversion

  48 weeks

Study Arms (2)

Combination group

EXPERIMENTAL

Maintain NAs treatment while add 48-week standard treatment by Peginterferon alfa 2a 180µg/week

Drug: Peginterferon alfa-2a

Mono NA group

NO INTERVENTION

Maintain NAs mono-therapy oral-daily for 48 weeks.

Interventions

Peginterferon alfa-2a DRUG

180ug/0.5ml,hypodermic injection once a week

Also known as: Pegasys

Combination group

Eligibility Criteria

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

You may qualify if:

• Male and female patients \>18 and ≤65 years of age;
• Diagnosed chronic hepatitis B (HBsAg(+) for over 6 months before nucleos(t)ide analogues treatment)
• Patients had achieved HBV DNA\<15 IU/ml、HBeAg\<100 PEIU/ml、HBsAg positive and HBsAg\<1500 IU/ml on treatment of Nucleoside (acid) Analogues (including LAM, ADV, ETV, and TDF )

You may not qualify if:

• Decompensated liver disease: including ascites, hepatic encephalopathy, esophagogastric-varicosis and fissure bleeding and other decompensated complication;
• Hypersensitive to interferon(IFN) or its active substance, and ineligible to IFN;
• A history of immunoregulation drug therapy within 1 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 100ng/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;
• Patients unsuitable for the research;

Sponsors & Collaborators

• Henan Provincial People's Hospital: lead

Study Sites (5)

Kaifeng Central Hospitl

Kaifeng, Henan, China

Location

Weishi County People's Hospital

Kaifeng, Henan, China

Location

Luoyang Central Hospital

Luoyang, Henan, China

Location

Shangqiu No.1 People's Hospital

Shangqiu, Henan, China

Location

Henan People's Hospital

Zhengzhou, Henan, China

Location

Related Publications (20)

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

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• 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.

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• Lai CL, Gane E, Liaw YF, Hsu CW, Thongsawat S, Wang Y, Chen Y, Heathcote EJ, Rasenack J, Bzowej N, Naoumov NV, Di Bisceglie AM, Zeuzem S, Moon YM, Goodman Z, Chao G, Constance BF, Brown NA; Globe Study Group. Telbivudine versus lamivudine in patients with chronic hepatitis B. N Engl J Med. 2007 Dec 20;357(25):2576-88. doi: 10.1056/NEJMoa066422.

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• Marcellin P, Heathcote EJ, Buti M, Gane E, de Man RA, Krastev Z, Germanidis G, Lee SS, Flisiak R, Kaita K, Manns M, Kotzev I, Tchernev K, Buggisch P, Weilert F, Kurdas OO, Shiffman ML, Trinh H, Washington MK, Sorbel J, Anderson J, Snow-Lampart A, Mondou E, Quinn J, Rousseau F. Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic hepatitis B. N Engl J Med. 2008 Dec 4;359(23):2442-55. doi: 10.1056/NEJMoa0802878.

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• Chang TT, Gish RG, de Man R, Gadano A, Sollano J, Chao YC, Lok AS, Han KH, Goodman Z, Zhu J, Cross A, DeHertogh D, Wilber R, Colonno R, Apelian D; BEHoLD AI463022 Study Group. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. N Engl J Med. 2006 Mar 9;354(10):1001-10. doi: 10.1056/NEJMoa051285.

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• 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

• Chevaliez S, Hezode C, Bahrami S, Grare M, Pawlotsky JM. Long-term hepatitis B surface antigen (HBsAg) kinetics during nucleoside/nucleotide analogue therapy: finite treatment duration unlikely. J Hepatol. 2013 Apr;58(4):676-83. doi: 10.1016/j.jhep.2012.11.039. Epub 2012 Dec 3.

  PMID: 23219442 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.

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• 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.

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• Lau GK, Piratvisuth T, Luo KX, Marcellin P, Thongsawat S, Cooksley G, Gane E, Fried MW, Chow WC, Paik SW, Chang WY, Berg T, Flisiak R, McCloud P, Pluck N; Peginterferon Alfa-2a HBeAg-Positive Chronic Hepatitis B Study Group. Peginterferon Alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis B. N Engl J Med. 2005 Jun 30;352(26):2682-95. doi: 10.1056/NEJMoa043470.

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• Liaw YF, Jia JD, Chan HL, Han KH, Tanwandee T, Chuang WL, Tan DM, Chen XY, Gane E, Piratvisuth T, Chen L, Xie Q, Sung JJ, Wat C, Bernaards C, Cui Y, Marcellin P. Shorter durations and lower doses of peginterferon alfa-2a are associated with inferior hepatitis B e antigen seroconversion rates in hepatitis B virus genotypes B or C. Hepatology. 2011 Nov;54(5):1591-9. doi: 10.1002/hep.24555.

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• 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.

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• Ren H, Hu P, Jia S. et al. A multi-center randomized study on the efficacy and safety of switching to peginterferon a-2a(40KD) for 48 or 96 weeks in HBeAg positive CHB patients with a prior NUC history for 1-3 years: an interim analysis of NEW SWITCH study. 2014 AASLD. LB10.

  RESULT

• 李国军，喻一奇，等。乙型肝炎表面抗原水平对核苷(酸)类似物序贯联合聚乙二醇干扰素a-2a治疗慢性乙型肝炎患者的疗效预测。中华传染病杂志2014.32（2）:100-106

  RESULT

• Chi H, Xie Q, Zhang NP. et al. Addition of Peginterferon Alfa-2b During Long-term Nucleos(t)ide Analogue Therapy Increases HBeAg Seroconversion and HBsAg Decline - Week 48 Results From a Multicenter Randomized Controlled Trial (PEGON Study). 2014 AASLD ab.1882.

  RESULT

• Marc Bourlière, Pascaline Rabiega. et al. HBsAg clearance after addition of 48 weeks of PEGIFN in HBeAg negative CHB patients on Nucleos(t)ide therapy with undetectable HBV DNA for at least one year: a multicenter randomized controlled phase III trial ANRS-HB06 PEGAN study: preliminary findings. 2014 AASLD ab1863.

  RESULT

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  PMID: 23245604 RESULT

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

• Jia Shang, M.D.

  Henan People's hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D.

Study Record Dates

• First Submitted: August 31, 2016
• First Posted: September 9, 2016
• Study Start: September 1, 2016
• Primary Completion: June 1, 2018
• Study Completion: December 1, 2018
• Last Updated: September 12, 2016

Record last verified: 2016-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (5)