Chronic Hepatitis BPhase 4StopNCT01911156
Sustained Off-treatment Response After HBeAg Loss in Chronic Hepatitis B Patients Treated With Nucleos(t)Ide Analogues
A Phase 4 study testing Continue NA treatment and Discontinue NA Treatment in people with Chronic Hepatitis B, run by University Health Network, Toronto at 2 sites in Canada.
Trial summary
This is a prospective randomized, open-label, phase IV clinical trial to learn the effects, good and/or bad, of discontinuing or continuing nucleos(t)ide analogue (NA) treatment for 72 weeks in participants with chronic hepatitis B infection whose immune system is controlling the amount of virus levels in the blood… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Hepatitis B
- What is being tested?
- Continue NA treatment and Discontinue NA Treatment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 2 sitesCanada
- Study dates
- Jul 2013to Mar 2016
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Chronic hepatitis B (HBsAg positive > 6 months)
- Currently on NA monotherapy and for ≥1 year prior to screening
- HBeAg negative with anti-HBe antibodies and HBV DNA undetectable at least once at 12 or more months prior to screening and at screening (HBV DNA assay should have lower limit of quantification of at least 50 IU/mL)
- Documented HBeAg positive before start of NA monotherapy
- Age > 18 years
- Written informed consent
Who cannot join
- Treatment with any investigational drug within 30 days of screening
- Severe hepatitis activity as documented by ALT >10x ULN
- Creatinine clearance <70 ml/min
- Presence of cirrhosis as documented by biopsy within 5 years, fibroscan >9kPa, or fibrotest >0.48
- Pre-existent neutropenia (neutrophils ≤1,000/mm3)
- Co-infection with hepatitis C virus and/or human immunodeficiency virus (HIV)
Show all 15Show fewer
- Other acquired or inherited causes of liver disease
- Alpha fetoprotein >50 ng/ml
- Hyper- or hypothyroidism
- Immune suppressive treatment within the previous 6 months
- Pregnancy, lactation
- Other significant medical illnesses that might interfere with this study
- Any medical condition requiring, or likely to require chronic systemic administration of steroids, during the course of the study
- Substance abuse (alcohol (≥80 g/day)and inhaled drugs (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
2 sites in 1 country.
Canada2 sites, 2 recruiting
- Recruiting
University Health Network
Toronto, Ontario, M5T 2S8
Victor Lo, MASc, CCRP, 416-603-5839, victor.lo@uhn.ca
Ambreen Arif
- Recruiting
University Health Network
Toronto, Ontario, M5T 2S8
Victor Lo, 416-603-5839, victor.lo@uhn.ca
Ambreen Arif, Ambreen.Arif@uhnresearch.ca
About this study
Official title: Sustained Off-treatment Response After HBeAg Loss in HBeAg-Pos Chronic Hepatitis B Patients Treated With Nucleos(t)Ide Analogues
This is a prospective randomized, open-label, phase IV clinical trial to learn the effects, good and/or bad, of discontinuing or continuing nucleos(t)ide analogue (NA) treatment for 72 weeks in participants with chronic hepatitis B infection whose immune system is controlling the amount of virus levels in the blood for at least 12 months of NA therapy.
About 66 adult men and women will participate in this study from University Health Network which includes the Toronto Western Hospital for about 72 weeks.
Read the detailed description
Chronic infection with the hepatitis B virus (HBV) is prevalent world-wide (estimated to affect 360 million individuals).
Chronic hepatitis b may result in progressive liver disease that leads to cirrhosis, end-stage liver disease and hepatocellular carcinoma (HCC). Chronic hepatitis B can also be benign and non-progressive, evolving into an inactive carrier state that rarely leads to significant liver injury or HCC. Over the last few years, several highly effective antiviral agents have been developed and approved for use in the treatment of chronic hepatitis B. Current therapy of chronic hepatitis B (CHB) aims at stopping progression to cirrhosis and hepatocellular carcinoma.
This is a prospective randomized, open-label, phase IV clinical trial to learn the effects, good and/or bad, of discontinuing or continuing NA treatment for 72 weeks in participants with chronic hepatitis B infection whose immune system is controlling the amount of virus levels in the blood for at least 12 months of NA therapy.
About 66 adult men and women will participate in this study from University Health Network which includes the Toronto Western Hospital for about 72 weeks.
- Conditions
- Chronic Hepatitis B
- Being tested
- Continue NA treatment, Discontinue NA Treatment
- Keywords
- Chronic Hepatitis B
- 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.
Continue NA treatmentDrug
Prescribed NA during the 72 week study period
Discontinue NA TreatmentDrug
Discontinue NA Treatment
| Study group | Role | What they receive |
|---|---|---|
| Discontinue NA treatment | Other | Subjects will not receive NA during the 72 week study period Receives: Drug: Discontinue NA Treatment |
| NA treatment | Other | Subjects will continue to receive their prescribed NA during the 72 week study period Receives: Drug: Continue NA treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sustained response, defined as the presence of an HBV DNA level <2000 IU/ml at week 48 in patients with a combined response at baseline
Measured: Outcome of patients in whom NA monotherapy is stopped at week 0 and of patients who continue to receive NA monotherapy up till week 72
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2013 (estimated)
- Study startJul 2013
- Primary completionJan 2016 (estimated)
- Study completionMar 2016 (estimated)
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.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- 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
- 66 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Harry Janssen, Prof., Principal investigator, University Heath Network
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01911156
- Sponsor's protocol ID
- Stop Study
- Other IDs
- GILEAD Sciences Canada, Inc.
- Acronym
- Stop
- Status last verified
- May 2015
- First submitted
- 25 Jun 2013
- Last updated
- 28 May 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Dongelmans EJ, Feld JJ, Boonstra A, Brakenhoff SM, Wong D, Yim C, Claassen M, Honkoop P, Hansen BE, de Man RA, Fung S, Berg T, van Bommel F, Janssen HLA, Sonneveld MJ. Early HBcrAg and Anti-HBc Levels Identify Patients at High Risk for Severe Flares After Nucleos(t)ide Analogue Cessation-A Pooled Analysis of Two Clinical Trials. Aliment Pharmacol Ther. 2025 Feb;61(3):570-578. doi: 10.1111/apt.18416. Epub 2024 Dec 3.
PubMed 39624922Liem KS, Chi H, Fung S, Wong DK, Yim C, Noureldin S, Chen J, de Man RA, Sarowar A, Feld JJ, Hansen BE, Hou J, Peng J, Janssen HLA. Early virologic relapse predicts alanine aminotransferase flares after nucleos(t)ide analogue withdrawal in patients with chronic hepatitis B. J Viral Hepat. 2022 Nov;29(11):986-993. doi: 10.1111/jvh.13742. Epub 2022 Sep 14.
PubMed 36048970Liem KS, Fung S, Wong DK, Yim C, Noureldin S, Chen J, Feld JJ, Hansen BE, Janssen HLA. Limited sustained response after stopping nucleos(t)ide analogues in patients with chronic hepatitis B: results from a randomised controlled trial (Toronto STOP study). Gut. 2019 Dec;68(12):2206-2213. doi: 10.1136/gutjnl-2019-318981. Epub 2019 Aug 28.
PubMed 31462554
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sustained Off-treatment Response After HBeAg Loss in HBeAg-Pos Chronic Hepatitis B Patients Treated With Nucleos(t)Ide Analogues
- ClinicalTrials.gov ID
- NCT01911156
- Acronym / sponsor ID
- Stop / Stop Study
- Conditions
- Chronic Hepatitis B
- Keywords
- Chronic Hepatitis B
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 66 participants (estimated)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Study start
- Jul 2013
- Primary completion
- Jan 2016 (estimated)
- Study completion
- Mar 2016 (estimated)
- First posted
- 30 Jul 2013 (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.
This is a prospective randomized, open-label, phase IV clinical trial to learn the effects, good and/or bad, of discontinuing or continuing nucleos(t)ide analogue (NA) treatment for 72 weeks in participants with chronic hepatitis B infection whose immune system is controlling the amount of virus levels in the blood for at least 12 months of NA therapy.
About 66 adult men and women will participate in this study from University Health Network which includes the Toronto Western Hospital for about 72 weeks.
Detailed description
Chronic infection with the hepatitis B virus (HBV) is prevalent world-wide (estimated to affect 360 million individuals).
Chronic hepatitis b may result in progressive liver disease that leads to cirrhosis, end-stage liver disease and hepatocellular carcinoma (HCC). Chronic hepatitis B can also be benign and non-progressive, evolving into an inactive carrier state that rarely leads to significant liver injury or HCC. Over the last few years, several highly effective antiviral agents have been developed and approved for use in the treatment of chronic hepatitis B. Current therapy of chronic hepatitis B (CHB) aims at stopping progression to cirrhosis and hepatocellular carcinoma.
This is a prospective randomized, open-label, phase IV clinical trial to learn the effects, good and/or bad, of discontinuing or continuing NA treatment for 72 weeks in participants with chronic hepatitis B infection whose immune system is controlling the amount of virus levels in the blood for at least 12 months of NA therapy.
About 66 adult men and women will participate in this study from University Health Network which includes the Toronto Western Hospital for about 72 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Discontinue NA treatment | Other | Drug: Discontinue NA TreatmentSubjects will not receive NA during the 72 week study period |
| NA treatment | Other | Drug: Continue NA treatmentSubjects will continue to receive their prescribed NA during the 72 week study period |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Chronic hepatitis B (HBsAg positive > 6 months)
- Currently on NA monotherapy and for ≥1 year prior to screening
- HBeAg negative with anti-HBe antibodies and HBV DNA undetectable at least once at 12 or more months prior to screening and at screening (HBV DNA assay should have lower limit of quantification of at least 50 IU/mL)
- Documented HBeAg positive before start of NA monotherapy
- Age > 18 years
Key exclusion criteria (15 listed)
- Treatment with any investigational drug within 30 days of screening
- Severe hepatitis activity as documented by ALT >10x ULN
- Creatinine clearance <70 ml/min
- Presence of cirrhosis as documented by biopsy within 5 years, fibroscan >9kPa, or fibrotest >0.48
- Pre-existent neutropenia (neutrophils ≤1,000/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 |
|---|---|---|
| Continue NA treatmentPrescribed NA during the 72 week study period | Drug | NA treatment |
| Discontinue NA TreatmentDiscontinue NA Treatment | Drug | Discontinue NA treatment |
Primary outcome
Sustained response, defined as the presence of an HBV DNA level <2000 IU/ml at week 48 in patients with a combined response at baseline
Time frame: Outcome of patients in whom NA monotherapy is stopped at week 0 and of patients who continue to receive NA monotherapy up till week 72
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2015.
- Derived from this study: PubMed 39624922Dongelmans EJ, Feld JJ, Boonstra A, Brakenhoff SM, Wong D, Yim C, Claassen M, Honkoop P, Hansen BE, de Man RA, Fung S, Berg T, van Bommel F, Janssen HLA, Sonneveld MJ. Early HBcrAg and Anti-HBc Levels Identify Patients at High Risk for Severe Flares After Nucleos(t)ide Analogue Cessation-A Pooled Analysis of Two Clinical Trials. Aliment Pharmacol Ther. 2025 Feb;61(3):570-578. doi: 10.1111/apt.18416. Epub 2024 Dec 3.
- Derived from this study: PubMed 36048970Liem KS, Chi H, Fung S, Wong DK, Yim C, Noureldin S, Chen J, de Man RA, Sarowar A, Feld JJ, Hansen BE, Hou J, Peng J, Janssen HLA. Early virologic relapse predicts alanine aminotransferase flares after nucleos(t)ide analogue withdrawal in patients with chronic hepatitis B. J Viral Hepat. 2022 Nov;29(11):986-993. doi: 10.1111/jvh.13742. Epub 2022 Sep 14.
- Derived from this study: PubMed 31462554Liem KS, Fung S, Wong DK, Yim C, Noureldin S, Chen J, Feld JJ, Hansen BE, Janssen HLA. Limited sustained response after stopping nucleos(t)ide analogues in patients with chronic hepatitis B: results from a randomised controlled trial (Toronto STOP study). Gut. 2019 Dec;68(12):2206-2213. doi: 10.1136/gutjnl-2019-318981. Epub 2019 Aug 28.
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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 Janssen, Prof. principal investigator
University Heath Network
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Continue NA treatment and Discontinue NA Treatment in people with Chronic Hepatitis B, run by University Health Network, Toronto at 2 sites in Canada.
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 6 inclusion and 15 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: status not confirmed, as of the sponsor's last update on 28 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Harry Janssen, MD (416-603-5986, harry.janssen@uhn.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Sustained response, defined as the presence of an HBV DNA level <2000 IU/ml at week 48 in patients with a combined response at baseline (time frame: Outcome of patients in whom NA monotherapy is stopped at week 0 and of patients who continue to receive NA monotherapy up till 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 NCT01911156, 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 28 May 2015.