Chronic Hepatitis BPhase 4PEGONNCT01532843
Lowering Viral Load With Nucleos(T)Ide Analogues Prior to Peginterferon Treatment to Ncrease Sustained Response in CHB
A Phase 4 study testing PegIFN alfa-2b in people with Chronic Hepatitis B, run by Foundation for Liver Research at 4 sites in 2 countries.
Trial summary
Treatment with a nucleoside analogue and subsequent viral decline has shown to partially restore immune hyporesponsiveness in chronic hepatitis B patients. Recent pilot studies investigating whether the effect of lowering viral load with nucleoside analogue therapy prior to the initiation of peginterferon results in… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Chronic Hepatitis B
- What is being tested?
- PegIFN alfa-2b
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 82 participants
- Where
- 4 sitesin 2 countries
- Study dates
- Jun 2012to Aug 2015
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Chronic hepatitis B (HBsAg positive > 6 months)
- HBeAg positive, anti-HBe negative within 4 weeks prior to initiation of peginterferon alfa-2b
- HBV DNA < 2000 IU/ml within one month prior to initiation of peginterferon alfa-2b after a minimum of 12 months treatment with either Entecavir (one of all 3 brands) or Tenofovir
- ALT < 5x ULN
- Compensated liver disease
- Age ≥ 18 years and ≤ 70 years
- Written informed consent
Who cannot join
- Treatment with any investigational drug within 30 days of entry to this protocol
- Treatment with Telbivudine
- Severe hepatitis activity as documented by ALT > 5 x ULN
- History of decompensated cirrhosis (defined as jaundice in the presence of cirrhosis, ascites, bleeding gastric or esophageal varices or encephalopathy)
- Pre-existent neutropenia (neutrophils < 1,500/mm3) or thrombocytopenia (platelets < 90,000/mm3)
- Co-infection with hepatitis C virus or human immunodeficiency virus (HIV)
Show all 16Show fewer
- Other acquired or inherited causes of liver disease: alcoholic liver disease, obesity induced liver disease, drug related liver disease, auto-immune hepatitis, hemochromatosis, Wilson's disease or alpha-1 antitrypsin deficiency
- Alpha fetoprotein > 50 ng/ml
- Hyper- or hypothyroidism (subjects requiring medication to maintain TSH levels in the normal range are eligible if all other inclusion/exclusion criteria are met)
- Immune suppressive treatment within the previous 6 months
- Contra-indications for alfa-interferon therapy like suspected hypersensitivity to interferon or Peginterferon or any known pre-existing medical condition that could interfere with the patient's participation in and completion of the study.
- Pregnancy, breast-feeding
- Other significant medical illness that might interfere with this study: significant pulmonary dysfunction in the previous 6 months, malignancy other than skin basocellular carcinoma in previous 5 years, immunodeficiency syndromes (e.g. HIV positivity, auto-immune diseases, organ transplants other than cornea and hair transplant)
- Any medical condition requiring, or likely to require chronic systemic administration of steroids, during the course of the study
- Substance abuse, such as alcohol (> 80 g/day), I.V. drugs and inhaled drugs in the past 2 years.
- Any other condition which in the opinion of the investigator would make the patient unsuitable for enrollment, or could interfere with the patient participating in and completing the study
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
China3 sites
Ruijin Hospital "Jiaolong University"
Shanghai, 200025
Public Health Center "Fu Dan University"
Shanghai, 200083
Zhong Shan Hospital "Fu Dan University"
Shanghai, 200083
About this study
Official title: Lowering Viral Load With Nucleos(T)Ide Analogues Prior to Peginterferon Alfa-2b Treatment to Increase Sustained Response in HBeAg-positive Chronic Hepatitis B (PEGON-study)
Treatment with a nucleoside analogue and subsequent viral decline has shown to partially restore immune hyporesponsiveness in chronic hepatitis B patients. Recent pilot studies investigating whether the effect of lowering viral load with nucleoside analogue therapy prior to the initiation of peginterferon results in higher sustained off-treatment responses showed contradictory findings.
The aim of this study is to investigate sustained off-treatment response to peginterferon alfa-2b in chronic HBeAg-positive hepatitis B patients who are pretreated with nucleos(t)ide analogues, thereby lowering viral load
- Conditions
- Chronic Hepatitis B
- Being tested
- PegIFN alfa-2b
- Keywords
- Hepatitis B, sustained response, peginterferon, nucleos(t)ide analogues
- Medical subject headings
- Hepatitis B, Chronic, Hepatitis B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PegIFN alfa-2bDrug
Also called Pegintron
Peginterferon alpha-2b 1.5 μg/kg per week s.c.for 48 weeks
| Study group | Role | What they receive |
|---|---|---|
| PegIFN alfa-2b + nucleos(t)ide analogue | Active comparator | Peginterferon alfa-2b 1.5 μg/kg per week s.c. for 48 weeks in addition to standard nucleos(t)ide analogue treatment Receives: Drug: PegIFN alfa-2b |
| Nucleos(t)ide analogue | No intervention | Continuation of Nucleos(t)ide analogue mono-therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sustained response
Sustained response to therapy, defined as the combined presence of HBeAg seroconversion and HBV DNA < 200 IU/mL
Measured: at week 72
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2012 (estimated)
- Study startJun 2012
- Primary completionAug 2015
- Study completionAug 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Chronic Hepatitis BStudies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 82 participants (actual)
Sponsor and investigators
- Lead sponsor
- Foundation for Liver Research
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Harry LA Janssen, MD PHD, Principal investigator, Erasmus MC, University Medical Center Rotterdam
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01532843
- Sponsor's protocol ID
- HBV 11-02
- Acronym
- PEGON
- Status last verified
- Jan 2019
- First submitted
- 10 Feb 2012
- Last updated
- 4 Jan 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Brakenhoff SM, de Knegt RJ, Oliveira J, van der Eijk AA, van Vuuren AJ, Hansen BE, Janssen HLA, de Man RA, Boonstra A, Sonneveld MJ. Levels of Antibodies to Hepatitis B Core Antigen Are Associated With Liver Inflammation and Response to Peginterferon in Patients With Chronic Hepatitis B. J Infect Dis. 2022 Dec 28;227(1):113-122. doi: 10.1093/infdis/jiac210.
PubMed 35599306Liem KS, van Campenhout MJH, Xie Q, Brouwer WP, Chi H, Qi X, Chen L, Tabak F, Hansen BE, Janssen HLA. Low hepatitis B surface antigen and HBV DNA levels predict response to the addition of pegylated interferon to entecavir in hepatitis B e antigen positive chronic hepatitis B. Aliment Pharmacol Ther. 2019 Feb;49(4):448-456. doi: 10.1111/apt.15098.
PubMed 30689258Chi H, Hansen BE, Guo S, Zhang NP, Qi X, Chen L, Guo Q, Arends P, Wang JY, Verhey E, de Knegt RJ, Xie Q, Janssen HLA. Pegylated Interferon Alfa-2b Add-on Treatment in Hepatitis B Virus Envelope Antigen-Positive Chronic Hepatitis B Patients Treated with Nucleos(t)ide Analogue: A Randomized, Controlled Trial (PEGON). J Infect Dis. 2017 Apr 1;215(7):1085-1093. doi: 10.1093/infdis/jix024.
PubMed 28329061
Study at a glance
From the registry record, last updated by the sponsor on 4 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lowering Viral Load With Nucleos(T)Ide Analogues Prior to Peginterferon Alfa-2b Treatment to Increase Sustained Response in HBeAg-positive Chronic Hepatitis B (PEGON-study)
- ClinicalTrials.gov ID
- NCT01532843
- Acronym / sponsor ID
- PEGON / HBV 11-02
- Conditions
- Chronic Hepatitis B
- Keywords
- Hepatitis B, sustained response, peginterferon, nucleos(t)ide analogues
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 82 participants (actual)
- Lead sponsor
- Foundation for Liver ResearchUniversity, hospital or other
- Study start
- Jun 2012
- Primary completion
- Aug 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 15 Feb 2012 (estimated)
- 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.
Treatment with a nucleoside analogue and subsequent viral decline has shown to partially restore immune hyporesponsiveness in chronic hepatitis B patients. Recent pilot studies investigating whether the effect of lowering viral load with nucleoside analogue therapy prior to the initiation of peginterferon results in higher sustained off-treatment responses showed contradictory findings.
The aim of this study is to investigate sustained off-treatment response to peginterferon alfa-2b in chronic HBeAg-positive hepatitis B patients who are pretreated with nucleos(t)ide analogues, thereby lowering viral load
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PegIFN alfa-2b + nucleos(t)ide analogue | Active comparator | Drug: PegIFN alfa-2bPeginterferon alfa-2b 1.5 μg/kg per week s.c. for 48 weeks in addition to standard nucleos(t)ide analogue treatment |
| Nucleos(t)ide analogue | No intervention | –Continuation of Nucleos(t)ide analogue mono-therapy |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Chronic hepatitis B (HBsAg positive > 6 months)
- HBeAg positive, anti-HBe negative within 4 weeks prior to initiation of peginterferon alfa-2b
- HBV DNA < 2000 IU/ml within one month prior to initiation of peginterferon alfa-2b after a minimum of 12 months treatment with either Entecavir (one of all 3 brands) or Tenofovir
- ALT < 5x ULN
- Compensated liver disease
Key exclusion criteria (16 listed)
- Treatment with any investigational drug within 30 days of entry to this protocol
- Treatment with Telbivudine
- Severe hepatitis activity as documented by ALT > 5 x ULN
- History of decompensated cirrhosis (defined as jaundice in the presence of cirrhosis, ascites, bleeding gastric or esophageal varices or encephalopathy)
- Pre-existent neutropenia (neutrophils < 1,500/mm3) or thrombocytopenia (platelets < 90,000/mm3)
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 |
|---|---|---|
| PegIFN alfa-2bAlso: PegintronPeginterferon alpha-2b 1.5 μg/kg per week s.c.for 48 weeks | Drug | PegIFN alfa-2b + nucleos(t)ide analogue |
Primary outcome
Sustained response
Time frame: at week 72
Sustained response to therapy, defined as the combined presence of HBeAg seroconversion and HBV DNA < 200 IU/mL
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jan 2019.
- Derived from this study: PubMed 35599306Brakenhoff SM, de Knegt RJ, Oliveira J, van der Eijk AA, van Vuuren AJ, Hansen BE, Janssen HLA, de Man RA, Boonstra A, Sonneveld MJ. Levels of Antibodies to Hepatitis B Core Antigen Are Associated With Liver Inflammation and Response to Peginterferon in Patients With Chronic Hepatitis B. J Infect Dis. 2022 Dec 28;227(1):113-122. doi: 10.1093/infdis/jiac210.
- Derived from this study: PubMed 30689258Liem KS, van Campenhout MJH, Xie Q, Brouwer WP, Chi H, Qi X, Chen L, Tabak F, Hansen BE, Janssen HLA. Low hepatitis B surface antigen and HBV DNA levels predict response to the addition of pegylated interferon to entecavir in hepatitis B e antigen positive chronic hepatitis B. Aliment Pharmacol Ther. 2019 Feb;49(4):448-456. doi: 10.1111/apt.15098.
- Derived from this study: PubMed 28329061Chi H, Hansen BE, Guo S, Zhang NP, Qi X, Chen L, Guo Q, Arends P, Wang JY, Verhey E, de Knegt RJ, Xie Q, Janssen HLA. Pegylated Interferon Alfa-2b Add-on Treatment in Hepatitis B Virus Envelope Antigen-Positive Chronic Hepatitis B Patients Treated with Nucleos(t)ide Analogue: A Randomized, Controlled Trial (PEGON). J Infect Dis. 2017 Apr 1;215(7):1085-1093. doi: 10.1093/infdis/jix024.
- Individual participant dataSharing planned: No
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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.
Harry LA Janssen, MD PHD principal investigator
Erasmus MC, University Medical Center Rotterdam
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing PegIFN alfa-2b in people with Chronic Hepatitis B, run by Foundation for Liver Research at 4 sites in 2 countries.
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 7 inclusion and 16 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: finished, as of the sponsor's last update on 4 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in China, Netherlands. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Sustained response (time frame: at week 72). 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 NCT01532843, which also lists 3 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 4 Jan 2019.