Chronic Hepatitis BPhase 3NCT01694264
Study of Anti-Viral Prophylaxis for HBsAg(+) or HBcAb(+)/HBsAb(-) Patients Starting Anti-TNFα
A Phase 3 study testing Entecavir in people with Chronic Hepatitis B and Rheumatoid Arthritis, run by Seoul National University Hospital at 22 sites in South Korea.
Trial summary
Analysis of effect of anti-TNFα treatment on HBV reactivation among patients with systemic rheumatic disease, especially rheumatoid arthritis Read more about this study
- Who is it for?
- Ages 16 to 85 years
- Conditions the study is for
- Chronic Hepatitis B, Rheumatoid Arthritis, Ankylosing Spondylitis
- What is being tested?
- Entecavir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 43 participants
- Where
- 22 sitesSouth Korea
- Study dates
- 1 Sep 2012to 31 Dec 2015
- Phase
- Phase 3
- 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 16 to 85 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Chronic hepatitis B, inactive HBsAg carriers or anti-HBc antibody positive patients with AST, ALT level equal or lower than 2x ULN
- Patient who has systemic rheumatic disease for which anti-TNFα treatment indication has been approved by the KFDA; rheumatoid arthritis (RA, 1987 ACR criteria), ankylosing spondylitis (AS, modified New York criteria), psoriatic arthritis (PsA, modified ESSG criteria), and juvenile rheumatoid arthritis (JRA, 1977 ACR criteria).
- Patient who is eligible to start anti-TNFα treatment (etanercept, infliximab, adalimumab, golimumab, and certolizumab pegol) due to treatment failure of other DMARDs against underlying RA, AS, PsA, or JRA. Patient who also fully understands that anti-TNFα agent expenses are not covered in this study.
- Patient who is willing and able to comply with the study drug regimen and all other study requirements
- Patient who is willing and able to provide a written informed consent to participate in the study
Who cannot join
- Patient who has liver cirrhosis or a history of hepatocellular carcinoma (HCC) or findings suggestive of HCC, such as suspicious foci or elevated serum alpha fetoprotein (AFP)
- Patient who received interferon or other immunomodulatory treatment for HBV infection in the 12 months before screening for this study
- Patient who has concomitant other chronic viral infection (HCV or HIV)
- Patient who is pregnant or breastfeeding or willing to be pregnant
- A history of chronic infection, recent serious or life-threatening infection. Especially,
- Patient with current clinical or laboratory evidence of active tuberculosis (TB) or latent TB unless there is documentation of prior anti-TB treatment was appropriate in duration according to the Korea Food and Drug Administration (KFDA) guidelines for management of latent TB in patients being treated with biologic agents
Show all 10Show fewer
- Patient with a history of herpes zoster within 2 months before screening for this study
- Active malignancy or a history of treated malignancy less than 5 years prior to screening
- Patients who are not cooperative or unable to comply with the study procedures
- Patients with any other condition which the investigator's judgment would make the patient unsuitable for inclusion in the study such as alcohol and drug abuse
Trial locations and contacts
22 sites in 1 country.
22 sites in 1 country
South Korea22 sites
Hallym University Sacred Heart Hospital
Anyang
Dong-A University, College of Medicine
Busan
Daegu Catholic Medical Center
Daegu
Kyungpook National University Hospital
Daegu
Chungnam National University Hospital
Daejun
Daejun Eulji University Hospital
Daejun
Chonnam National University Hospital
Gwangju
Gachon University Gil Medical Center
Incheon
Inha University Hospital
Incheon
Chonbuk National University Hospital
Jeonju
Seoul National University Hospital
Seoul, 110-744
Ewha Womans University Mokdong Hospital
Seoul
Hanyang University Hospital
Seoul
Konkuk University Hospital
Seoul
Korea University Guro Hospital
Seoul
Kyung Hee University Gangdong Hospital
Seoul
Kyunghee University Medical Center
Seoul
Severance Hospital
Seoul
SMG-SNU Boramae Medical Center
Seoul
The Catholic University of Korea, Seoul St. Mary's
Seoul
The Catholic University of Korea, Yeouido St. Mary's Hospital
Seoul
Ajou University Hospital
Suwon
About this study
Official title: A Randomized, Double-blinded, Phase 3, Multicenter, Investigator-initiated Trial for Entecavir for Prophylaxis of Hepatitis B Virus (HBV) Reactivation in HBV Surface Antigen or Anti-HBc Positive Patients Undergoing Anti-TNFα Treatment
Analysis of effect of anti-TNFα treatment on HBV reactivation among patients with systemic rheumatic disease, especially rheumatoid arthritis
Read the detailed description
Biologic agents, especially anti-TNFα treatments are widely used in inflammatory arthritis such as rheumatoid arthritis (RA) and ankylosing spondylitis (AS). More than 60% of RA or AS patients achieve good clinical response to anti-TNFα treatment. However, TNFα is also an important mediator participating in the normal immune response to infectious agents, in particular intracellular microorganisms in the human body. Therefore, opportunistic infections such as tuberculosis, viral and fungal infections have been of concern when using anti-TNFα agents. With accumulating experience, the treatment guideline for anti-TNFα therapy in latent tuberculosis is now well established. It is noteworthy that there are a number of case reports describing hepatitis B virus (HBV) reactivation in otherwise asymptomatic carriers who received anti-TNFα treatment. Anti-TNFα agents are now utilized as a promising treatment regimen for RA and AS treatment for even HBsAg carriers, yet there are still concerns of the risk of anti-TNFα therapy contributing to HBV reactivation. In our previous studies, we found that anti-viral therapy before starting anti-TNFα treatment may reduce the incidence of HBV reactivation, and that entecavir is likely more suitable in long-term prophylaxis for HBsAg carriers under anti-TNFα treatment. This justifies the need of a prospective trial that could demonstrate the long-term effects of prophylaxis in using anti-TNFα therapy in this subgroup of patients. It would help clinicians understand 1) whether anti-viral therapy is necessary in inactive HBsAg carriers initiating anti-TNFα treatment, and 2) at what time point would we most likely witness HBV reactivation after starting anti-TNFα therapy without anti-viral therapy coverage. In addition to established nationwide network of Rheumatologists working in major academic institutes in Korea, our division in Seoul National University Hospital has led many multi-center trials throughout the past years. In summary, the question of whether to combine anti-viral prophylaxis in HBsAg carriers starting anti-TNFα therapy is an important issue to Rheumatologists. There is no guideline for managing this subset of patients, and clinicians normally begin anti-viral therapy after the patient's liver function worsens. Therefore, our nationwide network of specialists proposes to launch a prospective study to investigate the benefit of anti-viral prophylaxis with entecavir in HBsAg carriers starting anti-TNFα treatment.
- Conditions
- Chronic Hepatitis B, Rheumatoid Arthritis, Ankylosing Spondylitis, Psoriatic Arthritis, Juvenile Idiopathic Arthritis
- Being tested
- Entecavir, Placebo
- Keywords
- HBV surface antigen, Anti-HBc positive, Anti-TNFα Treatment, Reactivation
- Medical subject headings
- Hepatitis B, Chronic, Arthritis, Rheumatoid, Spondylitis, Ankylosing, Arthritis, Psoriatic, Arthritis, Juvenile
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EntecavirDrug
Also called Baraclude (Bristol-Myers Squibb) 0.5mg
Entecavir (Baraclude (Bristol-Myers Squibb) 0.5mg.) will be taken orally on an empty stomach (2 hours after a meal or at least 2 hours before the next meal), once daily from 1 week before starting anti-TNFα and continue 72 weeks after anti-TNFα is administered.
PlaceboDrug
Also called placebo, prepared by Bristol-Myers Squibb
Placebo of Entecavir (prepared by Bristol-Myers Squibb) will be taken orally on an empty stomach (2 hours after a meal or at least 2 hours before the next meal), once daily from 1 week before starting anti-TNFα and continue 72 weeks after anti-TNFα is administered.
| Study group | Role | What they receive |
|---|---|---|
| Experimental Group | Experimental | Entecavir (Baraclude (Bristol-Myers Squibb) 0.5mg.) will be taken orally on an empty stomach (2 hours after a meal or at least 2 hours before the next meal), once daily from 1 week before starting anti-TNFα and continue 72 weeks after anti-TNFα is administered. Receives: Drug: Entecavir |
| Control Group | Placebo comparator | Placebo of Entecavir (prepared by Bristol-Myers Squibb) will be taken orally on an empty stomach (2 hours after a meal or at least 2 hours before the next meal), once daily from 1 week before starting anti-TNFα and continue 72 weeks after anti-TNFα is administered. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The frequency (events) of HBV reactivation
- Elevated HBV DNA titer: ≥1 log10 rise in HBV DNA level compared with baseline level (virologic breakthrough), along with
- Increase of AST or ALT above 32 x upper limit of normal (ULN) (biochemical breakthrough)
Measured: 48 weeks
Secondary outcomes (1)
Incidence of HBV reactivation among different anti-TNFα treatment groups
Measured: 72 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Sep 2012 (estimated)
- Study start1 Sep 2012
- Primary completion31 Aug 2015
- Study completion31 Dec 2015
Why it stopped: Delayed recruitment, unable to meet calculated sample size
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Hepatitis BStudies of the same condition, open and under way.
- More trials run by Seoul National University HospitalThe 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 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Seoul National University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Konkuk University Medical Center, Kyungpook National University Hospital, Kyunghee University Medical Center, Kyung Hee University Hospital at Gangdong, Gachon University Gil Medical Center, Daegu Catholic University Medical Center, Eulji University Hospital, SMG-SNU Boramae Medical Center, The Catholic University of Korea, Severance Hospital, Ajou University School of Medicine, Ewha Womans University Mokdong Hospital, Inha University Hospital, Chonnam National University Hospital, Chonbuk National University Hospital, Chungnam National University Hospital, Hallym University Medical Center, Hanyang University, Dong-A University, Korea University Guro Hospital
- Responsible party
- Principal investigator, Yeong-Wook Song, Seoul National University Hospital
- Investigators
- Yeong wook Song, MD, PhD, Principal investigator, Division of Rheumatology, Seoul National University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01694264
- Sponsor's protocol ID
- H-1112-073-390
- Status last verified
- Mar 2017
- First submitted
- 24 Sep 2012
- Last updated
- 6 Mar 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blinded, Phase 3, Multicenter, Investigator-initiated Trial for Entecavir for Prophylaxis of Hepatitis B Virus (HBV) Reactivation in HBV Surface Antigen or Anti-HBc Positive Patients Undergoing Anti-TNFα Treatment
- ClinicalTrials.gov ID
- NCT01694264
- Acronym / sponsor ID
- H-1112-073-390
- Conditions
- Chronic Hepatitis B, Rheumatoid Arthritis, Ankylosing Spondylitis, Psoriatic Arthritis, Juvenile Idiopathic Arthritis
- Keywords
- HBV surface antigen, Anti-HBc positive, Anti-TNFα Treatment, Reactivation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Delayed recruitment, unable to meet calculated sample size
- Enrolment
- 43 participants (actual)
- Lead sponsor
- Seoul National University HospitalUniversity, hospital or other
- Collaborators
- Konkuk University Medical Center, Kyungpook National University Hospital, Kyunghee University Medical Center, Kyung Hee University Hospital at Gangdong, Gachon University Gil Medical Center, Daegu Catholic University Medical Center, Eulji University Hospital, SMG-SNU Boramae Medical Center, The Catholic University of Korea, Severance Hospital, Ajou University School of Medicine, Ewha Womans University Mokdong Hospital, Inha University Hospital, Chonnam National University Hospital, Chonbuk National University Hospital, Chungnam National University Hospital, Hallym University Medical Center, Hanyang University, Dong-A University, Korea University Guro Hospital
- Study start
- 1 Sep 2012 (actual)
- Primary completion
- 31 Aug 2015 (actual)
- Study completion
- 31 Dec 2015 (actual)
- First posted
- 27 Sep 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.
Analysis of effect of anti-TNFα treatment on HBV reactivation among patients with systemic rheumatic disease, especially rheumatoid arthritis
Detailed description
Biologic agents, especially anti-TNFα treatments are widely used in inflammatory arthritis such as rheumatoid arthritis (RA) and ankylosing spondylitis (AS). More than 60% of RA or AS patients achieve good clinical response to anti-TNFα treatment. However, TNFα is also an important mediator participating in the normal immune response to infectious agents, in particular intracellular microorganisms in the human body. Therefore, opportunistic infections such as tuberculosis, viral and fungal infections have been of concern when using anti-TNFα agents. With accumulating experience, the treatment guideline for anti-TNFα therapy in latent tuberculosis is now well established. It is noteworthy that there are a number of case reports describing hepatitis B virus (HBV) reactivation in otherwise asymptomatic carriers who received anti-TNFα treatment. Anti-TNFα agents are now utilized as a promising treatment regimen for RA and AS treatment for even HBsAg carriers, yet there are still concerns of the risk of anti-TNFα therapy contributing to HBV reactivation. In our previous studies, we found that anti-viral therapy before starting anti-TNFα treatment may reduce the incidence of HBV reactivation, and that entecavir is likely more suitable in long-term prophylaxis for HBsAg carriers under anti-TNFα treatment. This justifies the need of a prospective trial that could demonstrate the long-term effects of prophylaxis in using anti-TNFα therapy in this subgroup of patients. It would help clinicians understand 1) whether anti-viral therapy is necessary in inactive HBsAg carriers initiating anti-TNFα treatment, and 2) at what time point would we most likely witness HBV reactivation after starting anti-TNFα therapy without anti-viral therapy coverage. In addition to established nationwide network of Rheumatologists working in major academic institutes in Korea, our division in Seoul National University Hospital has led many multi-center trials throughout the past years. In summary, the question of whether to combine anti-viral prophylaxis in HBsAg carriers starting anti-TNFα therapy is an important issue to Rheumatologists. There is no guideline for managing this subset of patients, and clinicians normally begin anti-viral therapy after the patient's liver function worsens. Therefore, our nationwide network of specialists proposes to launch a prospective study to investigate the benefit of anti-viral prophylaxis with entecavir in HBsAg carriers starting anti-TNFα treatment.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental Group | Experimental | Drug: EntecavirEntecavir (Baraclude (Bristol-Myers Squibb) 0.5mg.) will be taken orally on an empty stomach (2 hours after a meal or at least 2 hours before the next meal), once daily from 1 week before starting anti-TNFα and continue 72 weeks after anti-TNFα is administered. |
| Control Group | Placebo comparator | Drug: PlaceboPlacebo of Entecavir (prepared by Bristol-Myers Squibb) will be taken orally on an empty stomach (2 hours after a meal or at least 2 hours before the next meal), once daily from 1 week before starting anti-TNFα and continue 72 weeks after anti-TNFα is administered. |
Who may qualify
- Ages
- 16 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Chronic hepatitis B, inactive HBsAg carriers or anti-HBc antibody positive patients with AST, ALT level equal or lower than 2x ULN
- Patient who has systemic rheumatic disease for which anti-TNFα treatment indication has been approved by the KFDA; rheumatoid arthritis (RA, 1987 ACR criteria), ankylosing spondylitis (AS, modified New York criteria), psoriatic arthritis (PsA, modified ESSG criteria), and juvenile rheumatoid arthritis (JRA, 1977 ACR criteria).
- Patient who is eligible to start anti-TNFα treatment (etanercept, infliximab, adalimumab, golimumab, and certolizumab pegol) due to treatment failure of other DMARDs against underlying RA, AS, PsA, or JRA. Patient who also fully understands that anti-TNFα agent expenses are not covered in this study.
- Patient who is willing and able to comply with the study drug regimen and all other study requirements
- Patient who is willing and able to provide a written informed consent to participate in the study
Key exclusion criteria (10 listed)
- Patient who has liver cirrhosis or a history of hepatocellular carcinoma (HCC) or findings suggestive of HCC, such as suspicious foci or elevated serum alpha fetoprotein (AFP)
- Patient who received interferon or other immunomodulatory treatment for HBV infection in the 12 months before screening for this study
- Patient who has concomitant other chronic viral infection (HCV or HIV)
- Patient who is pregnant or breastfeeding or willing to be pregnant
- A history of chronic infection, recent serious or life-threatening infection. Especially,
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 |
|---|---|---|
| EntecavirAlso: Baraclude (Bristol-Myers Squibb) 0.5mgEntecavir (Baraclude (Bristol-Myers Squibb) 0.5mg.) will be taken orally on an empty stomach (2 hours after a meal or at least 2 hours before the next meal), once daily from 1 week before starting anti-TNFα and continue 72 weeks after anti-TNFα is administered. | Drug | Experimental Group |
| PlaceboAlso: placebo, prepared by Bristol-Myers SquibbPlacebo of Entecavir (prepared by Bristol-Myers Squibb) will be taken orally on an empty stomach (2 hours after a meal or at least 2 hours before the next meal), once daily from 1 week before starting anti-TNFα and continue 72 weeks after anti-TNFα is administered. | Drug | Control Group |
Primary outcome
The frequency (events) of HBV reactivation
Time frame: 48 weeks
1. Elevated HBV DNA titer: ≥1 log10 rise in HBV DNA level compared with baseline level (virologic breakthrough), along with 2. Increase of AST or ALT above 32 x upper limit of normal (ULN) (biochemical breakthrough)
1 secondary outcome
Incidence of HBV reactivation among different anti-TNFα treatment groups
Time frame: 72 weeks
Results and safety
The study was stopped early (reason given: Delayed recruitment, unable to meet calculated sample size). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2017.
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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.
Yeong wook Song, MD, PhD principal investigator
Division of Rheumatology, Seoul National University Hospital
22 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Entecavir in people with Chronic Hepatitis B and Rheumatoid Arthritis, run by Seoul National University Hospital at 22 sites in South Korea.
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 5 inclusion and 10 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: stopped early, as of the sponsor's last update on 6 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in South Korea. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 was stopped early (reason given: Delayed recruitment, unable to meet calculated sample size). Results are not available in the source record.
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?
The frequency (events) of HBV reactivation (time frame: 48 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 6 Mar 2017.