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

Chronic Hepatitis B Clinical Trial

Official title:

A Randomized, Open-label, Multi-center Clinical Trial to Evaluate Addition of Peginterferon Alfa-2a to CHB Patients Treated With NAs and Achieved HBV DNA<15 IU/ml、HBeAg<100 PEIU/ml、HBsAg Positive and HBsAg<1500 IU/ml.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02894918
• Other study ID #: COMBINE
• Status: Active, not recruiting
• Phase: Phase 4
• First received: August 31, 2016
• Last updated: September 8, 2016
• Start date: September 2016
• Est. completion date: December 2018

Study information

• Verified date: September 2016
• Source: Henan Provincial Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Ethics Commitee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 114
• Est. completion date: December 2018
• Est. primary completion date: June 2018
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• 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 )

Exclusion Criteria:

• 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;

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• Peginterferon alfa-2a
180ug/0.5ml,hypodermic injection once a week

Locations

Country	Name	City	State
China	Kaifeng Central Hospitl	Kaifeng	Henan
China	Weishi County People's Hospital	Kaifeng	Henan
China	Luoyang Central Hospital	Luoyang	Henan
China	Shangqiu No.1 People's Hospital	Shangqiu	Henan
China	Henan People's Hospital	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Henan Provincial Hospital

Country where clinical trial is conducted

China, 

References & Publications (20)

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Chevaliez S, Hézode 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.2012.1 — View Citation

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

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. Erratum in: J Hepatol. 2013 Jan;58( — View Citation

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Liaw YF, Gane E, Leung N, Zeuzem S, Wang Y, Lai CL, Heathcote EJ, Manns M, Bzowej N, Niu J, Han SH, Hwang SG, Cakaloglu Y, Tong MJ, Papatheodoridis G, Chen Y, Brown NA, Albanis E, Galil K, Naoumov NV; GLOBE Study Group. 2-Year GLOBE trial results: telbivu — View Citation

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 hepat — View Citation

Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, Abraham J, Adair T, Aggarwal R, Ahn SY, Alvarado M, Anderson HR, Anderson LM, Andrews KG, Atkinson C, Baddour LM, Barker-Collo S, Bartels DH, Bell ML, Benjamin EJ, Bennett D, Bhalla K, Bikbov B, — View Citation

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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 ANR

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 I — View Citation

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 — View Citation

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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: 10.101 — View Citation

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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 stud

* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Decline of HBeAg quantification	Quantitative HBeAg reduction at Weeks 12, 24 and 48 compared with baseline level. Quantitative HBeAg value unit was calculated using 'Paul Ehrlich Institute units per millilitre' (PEIU/ml).	12 weeks, 24 weeks, 48 weeks of treatment	No
Secondary	Decline of HBsAg quantification	Quantitative HBsAg reduction at Weeks 12, 24 and 48 compared with baseline level. Quantitative HBsAg calculated using 'International Units Per Millilitre' (IU/mL).	12 weeks, 24 weeks, 48 weeks of treatment	No
Secondary	The rate of HBeAg loss		48 weeks	No
Secondary	The rate of HBeAg seroconversion		48 weeks	No
Secondary	The rate of HBsAg seroconversion		48 weeks	No
Secondary	Sustained virological response rate	Sustained virological response rate will be presented as rate of HBV DNA <15 IU/ml	12 weeks, 24 weeks, 48 weeks of treatment	No