Hepatitis B, ChronicPhase 4NCT04035837

The Clinical Cure Project of Chronic Hepatitis B in China

A Phase 4 study testing pegylated interferon-alfa in people with Hepatitis B, Chronic, run by Third Affiliated Hospital, Sun Yat-Sen University at 1 site in China.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 to 60 years
Conditions the study is for: Hepatitis B, Chronic
What is being tested?: pegylated interferon-alfa
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 30,000 participants
Where: 1 siteChina
Study dates: 16 May 2018to 30 Jun 2026
Phase: Phase 4
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 60 years
All sexes
No healthy volunteers
Adult

Who may be able to join

according with the diagnosis of chronic hepatitis B in the guideline of China in 2015
18-60 years old
more than 1 year history of nucleot(s)ide analogues therapy with HBsAg ≤1500 IU/ml, negative HBeAg and HBV DNA<100 IU/ml
no contraindications of interferon

Who cannot join

Allergy to interferon
Alanine transaminase >10 times of upper limit of normal(ULN) or total bilirubin >2 times of ULN
existing or previous decompensated liver cirrhosis
White blood cells or Platelet below the lower limit of normal
existing severe organ injury
combined with autoimmune diseases, psychiatric diseases, diabetes or thyroidism

Show all 13Show fewer

confirmed or suspected malignant tumors
before or after transplantation
using immunosuppressor
pregnant or having a planned parenthood in 2 years
alcohol or drug addicted
infected by HIV
any conditions that is unsuitable to interferon therapy according to the doctors' judgement

Trial locations and contacts

1 site in 1 country.

China1 site

Department of Infectious Diseases, The Third Affliated Hospital of Sun Yat-sen University
Guangzhou, Guangdong, 510630

Other trials in China

About this study

Official title: A Study of Peg-interferon Treatment for Nucleos(t)Ide Analogues Suppressed Chronic Hepatitis B Patients With Low Level Hepatitis Surface Antigen

Chronic hepatitis B is a global public health problem, with nearly 700,000 deaths each year because of hepatitis B-related diseases. Recent studies have found that some patients who have used nucleot(s)ide analogues(NAs) for some period can achieve higher hepatitis B surface antigen(HBsAg) clearance rate(which is called clinical cure or functional cure) by using pegylated interferon. Patients who achieve clinical cure will further reduce liver inflammation, fibrosis and risks of liver cirrhosis and cancer in the future. This study was initiated in May 2018 and plans to recruit 30,000 eligible patients. The enrollment conditions are as follows: 1. according with the diagnosis of chronic hepatitis B in the guideline of China in 2015; 2.18-60 years old; 3. more than 1 year history of NAs therapy with HBsAg ≤1500 IU/ml, negative hepatitis e antigen and hepatitis B virus DNA<100 IU/ml; 4. no contraindications of interferon. For the above patients, pegylated interferon was used for 1-2 years(combined with NAs for at least 3 months).The primary goal of this study is to find out the optimal treatment for clinical cure.

Conditions: Hepatitis B, Chronic
Being tested: pegylated interferon-alfa
Medical subject headings: Hepatitis B, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

pegylated interferon-alfaDrug
All the patients in this study will receive pegylated interferon for all course.

Study groups in NCT04035837
Study group	Role	What they receive
short-course combination group	Experimental	Nucleoside analogue is used during the first 3 months. Receives: Drug: pegylated interferon-alfa
full-course combination group	Experimental	Nucleoside analogue is used during all the course of study. Receives: Drug: pegylated interferon-alfa
Monotherapy group	Experimental	Only Peg-IFN is used during all the course of study. Receives: Drug: pegylated interferon-alfa

What is being measured

The primary outcome is the main question the study is designed to answer.

hepatitis B surface antigen
hepatitis B surface antigen should be tested by the reagents from Roche or Abbott, which is expressed by using IU/ml.
Measured: up to 48 weeks

Secondary outcomes (1)

hepatitis B surface antibody
hepatitis B surface antigen should be tested by the reagents from Roche or Abbott, which is expressed by using IU/ml.
Measured: up to 48 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

16 May 201830 Jun 2026

First posted29 Jul 2019
Study start16 May 2018
Primary completion31 Dec 2025 (estimated)
Study completion30 Jun 2026 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (14)Papers the sponsor has linked to this study.
Other trials for Hepatitis B, ChronicStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 30,000 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04035837
Sponsor's protocol ID: ZhuFeng Project
Status last verified: Dec 2024
First submitted: 13 Jul 2019
Last updated: 13 Apr 2025
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No: Study protocol would be shared with other researchers.

Publications

Fattovich G, Bortolotti F, Donato F. Natural history of chronic hepatitis B: special emphasis on disease progression and prognostic factors. J Hepatol. 2008 Feb;48(2):335-52. doi: 10.1016/j.jhep.2007.11.011. Epub 2007 Dec 4.
PubMed 18096267
Liaw YF, Chu CM. Hepatitis B virus infection. Lancet. 2009 Feb 14;373(9663):582-92. doi: 10.1016/S0140-6736(09)60207-5.
PubMed 19217993
Brunetto MR. A new role for an old marker, HBsAg. J Hepatol. 2010 Apr;52(4):475-7. doi: 10.1016/j.jhep.2009.12.020. Epub 2010 Jan 30. No abstract available.
PubMed 20185190
Liu J, Lee MH, Batrla-Utermann R, Jen CL, Iloeje UH, Lu SN, Wang LY, You SL, Hsiao CK, Yang HI, Chen CJ. A predictive scoring system for the seroclearance of HBsAg in HBeAg-seronegative chronic hepatitis B patients with genotype B or C infection. J Hepatol. 2013 May;58(5):853-60. doi: 10.1016/j.jhep.2012.12.006. Epub 2012 Dec 13.
PubMed 23246508
Tseng TC, Liu CJ, Su TH, Wang CC, Chen CL, Chen PJ, Chen DS, Kao JH. Serum hepatitis B surface antigen levels predict surface antigen loss in hepatitis B e antigen seroconverters. Gastroenterology. 2011 Aug;141(2):517-25, 525.e1-2. doi: 10.1053/j.gastro.2011.04.046. Epub 2011 Apr 28.
PubMed 21672542
Moucari R, Korevaar A, Lada O, Martinot-Peignoux M, Boyer N, Mackiewicz V, Dauvergne A, Cardoso AC, Asselah T, Nicolas-Chanoine MH, Vidaud M, Valla D, Bedossa P, Marcellin P. High rates of HBsAg seroconversion in HBeAg-positive chronic hepatitis B patients responding to interferon: a long-term follow-up study. J Hepatol. 2009 Jun;50(6):1084-92. doi: 10.1016/j.jhep.2009.01.016. Epub 2009 Mar 9.
PubMed 19376603
Dietary effects on diurnal variation in lipogenesis. Nutr Rev. 1987 May;45(5):157-8. doi: 10.1111/j.1753-4887.1987.tb06353.x. No abstract available.
PubMed 3601258
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.
PubMed 22436845
Thompson AJ, Nguyen T, Iser D, Ayres A, Jackson K, Littlejohn M, Slavin J, Bowden S, Gane EJ, Abbott W, Lau GK, Lewin SR, Visvanathan K, Desmond PV, Locarnini SA. Serum hepatitis B surface antigen and hepatitis B e antigen titers: disease phase influences correlation with viral load and intrahepatic hepatitis B virus markers. Hepatology. 2010 Jun;51(6):1933-44. doi: 10.1002/hep.23571.
PubMed 20512987
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.
PubMed 24915612
Xie C, Lin B, Mo Z, Fu L, Chen X, Yang J, Li G, Li J, Zeng Y, Gong G, Zhang W, Tang H, Guo Y, Wei J, Jiang J, Wu X, Lv R, Lin M, Yu Z, Shang J, Guan Y, Li J, Zhang L, Guo Q, Ye Q, Mao Q, Li Y, Xue X, Geng J, Mao X, Lian J, Lu X, Hu G, Bai H, Cai D, Liu Y, Zhang L, Mao Q, Li J, Chen H, Chang J, Li Q, Xie D, Deng H, Xu Q, Peng L, Yang X, Zhuang H, Gao Z. Peginterferon alpha-2b Enhances Hepatitis B Surface Antigen Loss in Nucleos(t)ide Analogue-Suppressed Low Hepatitis B Surface Antigen Chronic Hepatitis B Patients: Everest Study in China. Clin Gastroenterol Hepatol. 2026 Feb 2:S1542-3565(26)00057-1. doi: 10.1016/j.cgh.2026.01.029. Online ahead of print.
PubMed 41638418
Chang LJ, Hao CQ, Rao GR, Xu LL, Li J, Cheng Y, Zheng LJ, Wu CW, Chen HX, Chen ZR, Lian JQ, Wu SH, Luo LM, Zhang WL, Zhang Y. Recurrence risk factors for chronic hepatitis B virus-infected patients who achieve functional cure with pegylated interferon-alpha-2b-based therapy: a multicenter pilot study. Virol J. 2025 May 19;22(1):146. doi: 10.1186/s12985-025-02761-3.
PubMed 40390028
Wang Z, Wang X, Zhou L, Shi S, Hua Y, Feng Y. Safety and efficacy of 48-week pegylated interferon-alpha-2b therapy in patients with hepatitis B virus-related compensated liver cirrhosis: a pilot observational study. Front Med (Lausanne). 2024 Dec 4;11:1489671. doi: 10.3389/fmed.2024.1489671. eCollection 2024.
PubMed 39697201
Huang Q, Xiao X, Zhuang X, Chen W, Huang Y, Liao J, Wang W, Wang Y, Lu L, Liu Z, Huang J. Peripheral Circulating Exosomal-miRNAs Potentially Mediate the Sensitivity to Interferon Treatment in Chronic Hepatitis B Virus Patients. Viral Immunol. 2023 Apr;36(3):209-221. doi: 10.1089/vim.2022.0130. Epub 2023 Mar 21.
PubMed 36944116

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruitingPhase 2
A Study of Sequential Therapy With Daplusiran/Tomligisiran (DAP/TOM) Followed by Bepirovirsen in Participants Living With Chronic Hepatitis B (CHB)
Chronic Hepatitis B Virus Infection, Hepatitis B
RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C
Active, not recruitingPhase 2
Study of Bepirovirsen in Participants Living With Human Immunodeficiency Virus and Chronic Hepatitis B Virus Infection (B-Focus)
Hepatitis B
Active, not recruitingPhase 2
Long-term Follow-up Study to Evaluate Durability of Treatment Response in Previous Bepirovirsen Study Participants (B-Sure)
Hepatitis B
Enrolling by invitationPhase 1
A Phase I Clinical Trial of CPU-YL01 Injection in Patients With Chronic Hepatitis B.
Chronic Hepatitis B

All Hepatitis B, Chronic trials

Study at a glance

From the registry record, last updated by the sponsor on 13 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Study of Peg-interferon Treatment for Nucleos(t)Ide Analogues Suppressed Chronic Hepatitis B Patients With Low Level Hepatitis Surface Antigen
ClinicalTrials.gov ID: NCT04035837
Acronym / sponsor ID: ZhuFeng Project
Conditions: Hepatitis B, Chronic
Phase: Phase 4
Study type: Interventional
Recruitment status: Active, not recruiting
Enrolment: 30,000 participants (estimated)
Lead sponsor: Third Affiliated Hospital, Sun Yat-Sen UniversityUniversity, hospital or other
Study start: 16 May 2018 (actual)
Primary completion: 31 Dec 2025 (estimated)
Study completion: 30 Jun 2026 (estimated)
First posted: 29 Jul 2019 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
short-course combination group	Experimental	Drug: pegylated interferon-alfaNucleoside analogue is used during the first 3 months.
full-course combination group	Experimental	Drug: pegylated interferon-alfaNucleoside analogue is used during all the course of study.
Monotherapy group	Experimental	Drug: pegylated interferon-alfaOnly Peg-IFN is used during all the course of study.

Who may qualify

Ages: 18 to 60 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (4 listed)

according with the diagnosis of chronic hepatitis B in the guideline of China in 2015
18-60 years old
more than 1 year history of nucleot(s)ide analogues therapy with HBsAg ≤1500 IU/ml, negative HBeAg and HBV DNA<100 IU/ml
no contraindications of interferon

Key exclusion criteria (13 listed)

Allergy to interferon
Alanine transaminase >10 times of upper limit of normal(ULN) or total bilirubin >2 times of ULN
existing or previous decompensated liver cirrhosis
White blood cells or Platelet below the lower limit of normal
existing severe organ injury

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
pegylated interferon-alfaAll the patients in this study will receive pegylated interferon for all course.	Drug	Monotherapy group, full-course combination group, short-course combination group

Primary outcome

hepatitis B surface antigen
Time frame: up to 48 weeks
hepatitis B surface antigen should be tested by the reagents from Roche or Abbott, which is expressed by using IU/ml.

1 secondary outcome

hepatitis B surface antibody
Time frame: up to 48 weeks

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2025.
Background: PubMed 18096267Fattovich G, Bortolotti F, Donato F. Natural history of chronic hepatitis B: special emphasis on disease progression and prognostic factors. J Hepatol. 2008 Feb;48(2):335-52. doi: 10.1016/j.jhep.2007.11.011. Epub 2007 Dec 4.
Background: PubMed 19217993Liaw YF, Chu CM. Hepatitis B virus infection. Lancet. 2009 Feb 14;373(9663):582-92. doi: 10.1016/S0140-6736(09)60207-5.
Background: PubMed 20185190Brunetto MR. A new role for an old marker, HBsAg. J Hepatol. 2010 Apr;52(4):475-7. doi: 10.1016/j.jhep.2009.12.020. Epub 2010 Jan 30. No abstract available.
Background: PubMed 23246508Liu J, Lee MH, Batrla-Utermann R, Jen CL, Iloeje UH, Lu SN, Wang LY, You SL, Hsiao CK, Yang HI, Chen CJ. A predictive scoring system for the seroclearance of HBsAg in HBeAg-seronegative chronic hepatitis B patients with genotype B or C infection. J Hepatol. 2013 May;58(5):853-60. doi: 10.1016/j.jhep.2012.12.006. Epub 2012 Dec 13.
Background: PubMed 21672542Tseng TC, Liu CJ, Su TH, Wang CC, Chen CL, Chen PJ, Chen DS, Kao JH. Serum hepatitis B surface antigen levels predict surface antigen loss in hepatitis B e antigen seroconverters. Gastroenterology. 2011 Aug;141(2):517-25, 525.e1-2. doi: 10.1053/j.gastro.2011.04.046. Epub 2011 Apr 28.
Background: PubMed 19376603Moucari R, Korevaar A, Lada O, Martinot-Peignoux M, Boyer N, Mackiewicz V, Dauvergne A, Cardoso AC, Asselah T, Nicolas-Chanoine MH, Vidaud M, Valla D, Bedossa P, Marcellin P. High rates of HBsAg seroconversion in HBeAg-positive chronic hepatitis B patients responding to interferon: a long-term follow-up study. J Hepatol. 2009 Jun;50(6):1084-92. doi: 10.1016/j.jhep.2009.01.016. Epub 2009 Mar 9.
Background: PubMed 3601258Dietary effects on diurnal variation in lipogenesis. Nutr Rev. 1987 May;45(5):157-8. doi: 10.1111/j.1753-4887.1987.tb06353.x. No abstract available.
Background: PubMed 22436845European 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.
Background: PubMed 20512987Thompson AJ, Nguyen T, Iser D, Ayres A, Jackson K, Littlejohn M, Slavin J, Bowden S, Gane EJ, Abbott W, Lau GK, Lewin SR, Visvanathan K, Desmond PV, Locarnini SA. Serum hepatitis B surface antigen and hepatitis B e antigen titers: disease phase influences correlation with viral load and intrahepatic hepatitis B virus markers. Hepatology. 2010 Jun;51(6):1933-44. doi: 10.1002/hep.23571.
Background: PubMed 24915612Ning 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.
Derived from this study: PubMed 41638418Xie C, Lin B, Mo Z, Fu L, Chen X, Yang J, Li G, Li J, Zeng Y, Gong G, Zhang W, Tang H, Guo Y, Wei J, Jiang J, Wu X, Lv R, Lin M, Yu Z, Shang J, Guan Y, Li J, Zhang L, Guo Q, Ye Q, Mao Q, Li Y, Xue X, Geng J, Mao X, Lian J, Lu X, Hu G, Bai H, Cai D, Liu Y, Zhang L, Mao Q, Li J, Chen H, Chang J, Li Q, Xie D, Deng H, Xu Q, Peng L, Yang X, Zhuang H, Gao Z. Peginterferon alpha-2b Enhances Hepatitis B Surface Antigen Loss in Nucleos(t)ide Analogue-Suppressed Low Hepatitis B Surface Antigen Chronic Hepatitis B Patients: Everest Study in China. Clin Gastroenterol Hepatol. 2026 Feb 2:S1542-3565(26)00057-1. doi: 10.1016/j.cgh.2026.01.029. Online ahead of print.
Derived from this study: PubMed 40390028Chang LJ, Hao CQ, Rao GR, Xu LL, Li J, Cheng Y, Zheng LJ, Wu CW, Chen HX, Chen ZR, Lian JQ, Wu SH, Luo LM, Zhang WL, Zhang Y. Recurrence risk factors for chronic hepatitis B virus-infected patients who achieve functional cure with pegylated interferon-alpha-2b-based therapy: a multicenter pilot study. Virol J. 2025 May 19;22(1):146. doi: 10.1186/s12985-025-02761-3.
Individual participant dataSharing planned: No. Study protocol would be shared with other researchers.

Related trials for Hepatitis B, Chronic

Active, not recruitingPhase 2
A Study of Sequential Therapy With Daplusiran/Tomligisiran (DAP/TOM) Followed by Bepirovirsen in Participants Living With Chronic Hepatitis B (CHB)
Chronic Hepatitis B Virus Infection, Hepatitis B
RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C
Active, not recruitingPhase 2
Study of Bepirovirsen in Participants Living With Human Immunodeficiency Virus and Chronic Hepatitis B Virus Infection (B-Focus)
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Active, not recruitingPhase 2
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Enrolling by invitationPhase 1
A Phase I Clinical Trial of CPU-YL01 Injection in Patients With Chronic Hepatitis B.
Chronic Hepatitis B

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Zhiliang Gao study chair

Third Affiliated Hospital, Sun Yat-Sen University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing pegylated interferon-alfa in people with Hepatitis B, Chronic, run by Third Affiliated Hospital, Sun Yat-Sen University at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 13 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

hepatitis B surface antigen (time frame: up to 48 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04035837, which also lists 14 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2025.