Addition of PegIFN Alfa-2a to CHB Patients Treated With Nucleot(s)Ides

Hepatitis B Clinical Trial

Official title:

A Randomized, Controlled, Open-label, Multicenter Clinical Trial to Evaluate the Addition of PegIFN Alfa-2a to CHB Patients Treated With Nucleot(s)Ides

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02644538
• Other study ID #: APACE
• Status: Not yet recruiting
• Phase: Phase 4
• First received: December 28, 2015
• Last updated: December 30, 2015
• Start date: December 2015
• Est. completion date: December 2018

Study information

• Verified date: December 2015
• Source: The Second Affiliated Hospital of Chongqing Medical University
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

This study evaluates whether PegIFN alfa-2a add on can improve CHB patients HBsAg clearance at the end of 48 weeks treatment. The CHB patients who received nucleot(s)ides anti-virus treatment and reached HBV DNA<1000 copies/ml and HBsAg<3000 IU/ml, were randomly assigned into two groups: One group continue the nucleot(s)ides treatment for 72 weeks, the other add on PegIFN alfa-2a on the basis of the original treatment for 48 weeks, and follow up for 24 weeks.

Description:

nucleot(s)ides is a potent inhibitor of hepatitis B viral(HBV) replication, but long-term therapy may be required, and it is difficult for CHB patients to achieve HBsAg clearance by using nucleot(s)ides. Therefore, it is need take long-term therapy if chronic hepatitis B (CHB) choose to use nucleot(s)ides, and in another way, nucleot(s)ides resistance is an important clinical risk. More and more young patients want to stop treating, and discontinuation of nucleot(s)ides is a feasible strategy to reduce resistance. However, it is really easy to relapse if patients did not arrive HBsAg clearance. PegIFN alfa-2a can clear HBV by direct anti-viral and immune regulation mechanisms including enhancing natural killer cell response, increased cluster of differentiation 8(CD8 +) T lymphocytes and other mechanisms to restore and enhance the immune response in patients with CHB; and what's more, patients are safety after discontinuing.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 196
• Est. completion date: December 2018
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Male and female subjects,18-65 years

2. positive for hepatitis B surface antigen (HBsAg) and negative for antibodies to HBsAg (anti-HBs antibodies) for at least 6 months before NAs treated

3. nucleot(s)ides monotherapy (including lamivudine, adefovir, entecavir, tenofovir) and achieved HBV DNA<1000 copies/mL with HBsAg <3000 IU/mL, positive or negative for HBeAg, and negative for anti-HBs antibodies

4. Subjects with no contra-indications to Peginterferon alfa therapy as detailed in the label (Hypersensitivity to the active substance, to alpha interferon, or to any of the excipients; Autoimmune hepatitis; Severe hepatic dysfunction or decompensated cirrhosis of the liver; A history of severe pre-existing cardiac disease, including unstable or uncontrolled cardiac disease in the previous six months)

5. Subjects who are not co-infected with Hepatitis A Virus, Hepatitis C Virus or HIV

6. Female subjects not pregnant or breast feeding when Peginterferon alfa treatment commenced, and aware of the requirement to use an effective method of contraception during therapy

7. Written informed consent signed.

Exclusion Criteria:

1. positive for Hepatitis A Virus Ab, HCV-RNA or positive for Hepatitis C Virus Ab, HDV Ab, HEV Ab or positive for HIV Ab in screening period

2. 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

3. Compensated or Decompensated liver cirrhosis: with history of cirrhosis before nucleot(s)ides treatment or Child-Pugh score = 5 or Complications of liver cirrhosis such as ascites, hepatic encephalopathy, esophageal gastric varices bleeding

4. Autoimmune disease including Autoimmune hepatitis and Psoriasis and so on

5. Pregnant women and lactating women or patients with pregnancy plans and not willing to use contraception during the study period

6. A history of immunoregulation drug therapy within one year before entry including IFN and so on

7. Have a history of alcohol abuse

8. With severe psychiatric condition or nervous disease such as epilepsy, depression, mania, epilepsy, schizophrenia and so on

9. A neutrophil count of less than 1500 per cubic millimeter or a platelet count of less than 90,000 per cubic millimeter

10. Severe organ dysfunction

11. With other malignant tumors(exclude the cured ones)

12. Uncontrolled diabetes, hypertension or thyroid disease

13. A serum creatinine level that was more than 1.5 times the upper limit of the normal range

14. Hypersensitivity to interferon(IFN) or its active substance, and ineligible to IFN

15. Participate in other clinical studies at the same time

16. Patients unsuitable for the research -

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis B

Intervention

Drug:
• PegIFN alfa-2a
chronic hepatitis B patients who treated with nucleot(s)ides (including lamivudine, adefovir, entecavir, tenofovir) arrived HBV DNA <1000copies/ml, and HBsAg<3000IU/ml, then change the treatment to original nucleot(s)ides add on PegIFN alfa-2a, the combined treatment is for 48 weeks, and follow up for 24 weeks

Locations

Country	Name	City	State
n/a

Sponsors (4)

Lead Sponsor	Collaborator
The Second Affiliated Hospital of Chongqing Medical University	First Affiliated Hospital of Xinjiang Medical University, People's Hospital of Guizhou Province, The First Affiliated Hospital of Nanchang University

References & Publications (9)

Chen J, Wang Y, Wu XJ, Li J, Hou FQ, Wang GQ. Pegylated interferon a-2b up-regulates specific CD8+ T cells in patients with chronic hepatitis B. World J Gastroenterol. 2010 Dec 28;16(48):6145-50. — View Citation

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

Ganem D, Prince AM. Hepatitis B virus infection--natural history and clinical consequences. N Engl J Med. 2004 Mar 11;350(11):1118-29. Review. Erratum in: N Engl J Med. 2004 Sep 16;351(12):351. — View Citation

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 he — View Citation

Lu FM, Zhuang H. Management of hepatitis B in China. Chin Med J (Engl). 2009 Jan 5;122(1):3-4. — View Citation

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

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 — View Citation

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

Piratvisuth T, Marcellin P, Popescu M, Kapprell HP, Rothe V, Lu ZM. Hepatitis B surface antigen: association with sustained response to peginterferon alfa-2a in hepatitis B e antigen-positive patients. Hepatol Int. 2013 Jun;7(2):429-36. doi: 10.1007/s1207 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants who achieve HBsAg clearance	To investigate whether Peg-IFN alfa-2a add on treatment can improve the HBsAg clearance in CHB patients at the end of the treatment (48 week).	treat for 48 weeks	No
Secondary	Number of participants who achieve HBsAg seroconversion	To investigate whether Peg-IFN alfa-2a add on treatment can improve the HBsAg seroconversion in CHB patients at the end of the treatment (48 week).	48 weeks	No
Secondary	Number of participants who achieve HBeAg clearance and seroconversion	To investigate whether Peg-IFN alfa-2a add on treatment can improve HBeAg clearance and seroconversion at the end of the treatment (48 week).	48 weeks	No
Secondary	HBsAg changes from Baseline	Pegasys 24 weeks Group:12,24 weeks and Pegasys 48 weeks Group:12,24,48 weeks	12,24 and 48 weeks	No
Secondary	Number of participants who achieve HBV DNA<1000 copies/ml	To investigate whether Peg-IFN alfa-2a add on treatment can improve HBV DNA<1000 copies/ml	12,24 and 48 weeks	No