HBVPhase 4NCT05001672
The Efficacy of Prophylactic TAF for HBsAg-positive Patients Receiving bDMARDs
A Phase 4 study testing Tenofovir alafenamide in people with HBV and Inflammatory Arthritis, run by Taipei Veterans General Hospital, Taiwan.
Trial summary
Hepatitis B virus reactivation (HBVr) is an emerging issue and a potentially life-threatening complication to patients with history of Hepatitis B virus (HBV) infection whose immune system is deficient or suppressed. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- HBV, Inflammatory Arthritis
- What is being tested?
- Tenofovir alafenamide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 108 participants
- Where
- No sites listed yet
- Study dates
- 15 Aug 2021to 31 Dec 2025
- 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 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age >=20 years old;
- History of chronic hepatitis B with HBsAg-positive;
- Both HBeAg-positive and HBeAg-negative are allowed;
- Inflammatory arthritis (including psoriatic arthritis);
- On bDMARDs treatment or will start bDMARDs within in 4 weeks. The bDMARDs included all anti-TNF-α agents, rituximab (anti-CD20 monoclonal antibody), tocilizumab (anti-interleukin 6 receptor monoclonal antibody), abatacept (cytotoxic T-lymphocyte-associated antigen 4 immunoglobulin), and all new biologics with indication of IA treatment;
- No NUCs treatment in recent 6 months;
Show all 9Show fewer
- No limitation of the baseline HBV DNA level;
- Total bilirubin level <2 mg/dL;
- ALT < 2x ULN (<80 U/L).
Who cannot join
- Child-Pugh class >B7;
- Active EV bleeding within 4 weeks;
- History of hepatic encephalopathy or intractable ascites;
- Coexist with other primary liver diseases, such as active chronic hepatitis C, hepatitis D, autoimmune hepatitis, or Wilson's disease. (*HCV RNA undetectable is allowed to enroll);
- Active malignancy;
- Pregnant women.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: The Efficacy of TAF as a Prophylactic Antiviral Agent for HBsAg-positive Patients Receiving Biological DMARDs (bDMARDs)
Hepatitis B virus reactivation (HBVr) is an emerging issue and a potentially life-threatening complication to patients with history of Hepatitis B virus (HBV) infection whose immune system is deficient or suppressed. It is estimated that the risk of HBVr ranges 20%-50% in hepatitis B surface antigen (HBsAg)-positive patients undergoing chemotherapy or immunosuppressive therapy. Not only HBsAg-positive patients but also HBsAg-negative/antibody to hepatitis B core antigen (anti-HBc)-positive patients (resolved hepatitis B) have the risk of HBVr.
Recent studies also reported that the risk of HBVr associated with TNF-α inhibitor treatment widely ranged from 12.3% to 62.5%. Antiviral prophylaxis by nucleos(t)ide analogues (NUCs) is recommended for patients with high risk of HBVr according to 2018 AASLD guidance. Phase 3 studies reported that tenofovir alafenamide (Vemlidy, TAF) can effectively suppress HBV in both HBeAg-positive and HBeAg-negative chronic hepatitis B patients, and TAF is superior to TDF in safety profiles and ALT normalization. However, the evidence of TAF in prevention HBV reactivation for patients with HBsAg-positive and imflammatory arthritis, who need bDMARDs are still missing.
Read the detailed description
Hepatitis B virus (HBV) infection is the major cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. There are up to 248 million people worldwide chronically infected with HBV. HBV reactivation (HBVr) is an emerging issue and a potentially life-threatening complication to patients with history of HBV infection whose immune system is deficient or suppressed. It is estimated that the risk of HBVr ranges 20%-50% in hepatitis B surface antigen (HBsAg)-positive patients undergoing chemotherapy or immunosuppressive therapy. Not only HBsAg-positive patients but also HBsAg-negative/antibody to hepatitis B core antigen (anti-HBc)-positive patients (resolved hepatitis B) have the risk of HBVr. The investigator's studies have demonstrated that the risk of HBsAg seroreversion was 10% in diffuse large B cell lymphoma patients undergoing anti-CD20 (rituximab) treatment; and the risk of HBsAg reverse seroconversion in rheumatic arthritis (RA) patients with resolved HBV infection and received biological disease-modifying antirheumatic drugs (bDMARDs) or glucocorticoid (GC) treatment can persist for up to 10 years. In the investigator's previous study, it also be investigated the risk of HBVr under different immunosuppressant regimens in HBsAg-positive patients with RA, and the investigator pointed out immunosuppressive treatment with a combination of GC, synthetic disease-modifying antirheumatic drugs (sDMARDs), and bDMARDs has the highest risk of HBVr with annual incidence around 20%. Recent studies also reported that the risk of HBVr associated with TNF-α inhibitor treatment widely ranged from 12.3% to 62.5%.
Antiviral prophylaxis by nucleos(t)ide analogues (NUCs) is recommended for patients with high risk of HBVr according to 2018 AASLD guidance. Phase 3 studies reported that tenofovir alafenamide (Vemlidy, TAF) can effectively suppress HBV in both HBeAg-positive and HBeAg-negative chronic hepatitis B patients, and TAF is superior to TDF in safety profiles and ALT normalization. However, the evidence of TAF in prevention HBV reactivation for patients with HBsAg-positive and imflammatory arthritis, who need bDMARDs are still missing. Therefore, the investigator plans to conduct this randomized controlled trial to confirm the efficacy of TAF as a prophylactic antiviral agent for HBsAg-positive patients with inflammatory arthritis (IA) on bDMARDs treatment.
- Conditions
- HBV, Inflammatory Arthritis
- Being tested
- Tenofovir alafenamide
- Medical subject headings
- Arthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tenofovir alafenamideDrug
Also called Vemlidy, TAF
Tenofovir alafenamide (TAF, brand name: Vemlidy) is a hepatitis B virus nucleotide reverse transcriptase inhibitor oral medication for the treatment of chronic hepatitis B virus infection. It is a prodrug of tenofovir. Closely related to the commonly used reverse-transcriptase inhibitor tenofovir disoproxil fumarate, TAF has greater antiviral activity and better distribution into lymphoid tissues than that agent. Vemlidy was approved by the U.S. Food and Drug Administration (FDA) in November 2016 and the TAIWAN Food and Drug Administration (TFDA) in April 2017.
| Study group | Role | What they receive |
|---|---|---|
| TAF arm | Experimental | 54 patients will be randomized into TAF arm*. TAF 25 mg QD will be initiated 7 days before bDMARDs, and continued for up to 144-weeks.
*for patients received rituximab (anti-CD20 monoclonal antibody) will be enrolled into TAF arm, and TAF 25 mg QD will be initiated 7 days before rituximab, and continued for up to 144-weeks. Max 20 rituximab patients will be recruited. Receives: Drug: Tenofovir alafenamide |
| Observation arm | Other | 54 patients will be randomized into observation arm initially. These patients will be closely monitored their HBV status (including qHBsAg and HBV DNA) for 48 weeks. TAF 25 mg QD will be initiated for 144 weeks in the presence of HBV reactivation, or after 48 weeks of observation. Receives: Drug: Tenofovir alafenamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
1-year HBV reactivation rate
The assessment for the HBV reactivation is by the marker as hepatitis b viral load (unit: IU/ML).
Measured: Up to 1-year
Secondary outcomes (5)
Serial change of renal and liver function
The assessment for the renal function is by the markers as serum creatinine (unit: mg/dL), eGFR (unit: 60 mL/min/1.73M^2) and serum inorganic phosphorus (unit: mg/dL); for the liver function is by the markers as ALT/AST (unit: U/L) and child-pugh score.
The child-pugh score is determined by scoring five clinical measures of liver disease. A score of 1, 2, or 3 is given to each measure, with 3 being the most severe, and the five clinical measures are: total bilirubin (unit: mg/dL), serum albumin (unit: g/dL), prothrombin time (unit: sec), absence/presence of ascites and absence/presence of hepatic encephalopathy. The higher scores mean a worse outcome.
Measured: Up to 3-years
Observation of bone mineral density at 48-weeks, 96-weeks, and 144-weeks
The assessment for the bone mineral density is by the marker as T-score.
Measured: Up to 3-years
The 1-year virological remission rate
The assessment for the HBV reactivation is by the marker as hepatitis b viral load (unit: IU/ML).
Measured: Up to 1-year
The 1-year HBeAg seroconversion rate
The assessment for the HBeAg seroconversion is by the marker as HBeAg (unit: COI).
Measured: Up to 1-year
The adverse reactions and compliance
The assessment for the adverse reactions is by the CTCAE v5.0, and the compliance is by the residual study drug.
Measured: Up to 3-years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2021
- Study start15 Aug 2021 (estimated)
- Primary completion30 Jun 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HBVStudies of the same condition, open and under way.
- More trials run by Taipei Veterans General Hospital, TaiwanThe 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients who fulfilled in all inclusion and exclusion criteria will be randomized into TAF 25mg qd or observation arm in 1:1 ratio. * 54 patients will be randomized into TAF arm\*. * 54 patients will be randomized into observation arm initially.
- Masking
- None (open label)
- Enrolment
- 108 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Taipei Veterans General Hospital, Taiwan
- Sponsor type
- Other government
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05001672
- Sponsor's protocol ID
- IN-TW-320-6150
- Status last verified
- Aug 2021
- First submitted
- 2 Jul 2021
- Last updated
- 12 Aug 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Efficacy of TAF as a Prophylactic Antiviral Agent for HBsAg-positive Patients Receiving Biological DMARDs (bDMARDs)
- ClinicalTrials.gov ID
- NCT05001672
- Acronym / sponsor ID
- IN-TW-320-6150
- Conditions
- HBV, Inflammatory Arthritis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 108 participants (estimated)
- Lead sponsor
- Taipei Veterans General Hospital, TaiwanOther government
- Study start
- 15 Aug 2021 (estimated)
- Primary completion
- 30 Jun 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 12 Aug 2021 (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.
Hepatitis B virus reactivation (HBVr) is an emerging issue and a potentially life-threatening complication to patients with history of Hepatitis B virus (HBV) infection whose immune system is deficient or suppressed. It is estimated that the risk of HBVr ranges 20%-50% in hepatitis B surface antigen (HBsAg)-positive patients undergoing chemotherapy or immunosuppressive therapy. Not only HBsAg-positive patients but also HBsAg-negative/antibody to hepatitis B core antigen (anti-HBc)-positive patients (resolved hepatitis B) have the risk of HBVr.
Recent studies also reported that the risk of HBVr associated with TNF-α inhibitor treatment widely ranged from 12.3% to 62.5%. Antiviral prophylaxis by nucleos(t)ide analogues (NUCs) is recommended for patients with high risk of HBVr according to 2018 AASLD guidance. Phase 3 studies reported that tenofovir alafenamide (Vemlidy, TAF) can effectively suppress HBV in both HBeAg-positive and HBeAg-negative chronic hepatitis B patients, and TAF is superior to TDF in safety profiles and ALT normalization. However, the evidence of TAF in prevention HBV reactivation for patients with HBsAg-positive and imflammatory arthritis, who need bDMARDs are still missing.
Detailed description
Hepatitis B virus (HBV) infection is the major cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. There are up to 248 million people worldwide chronically infected with HBV. HBV reactivation (HBVr) is an emerging issue and a potentially life-threatening complication to patients with history of HBV infection whose immune system is deficient or suppressed. It is estimated that the risk of HBVr ranges 20%-50% in hepatitis B surface antigen (HBsAg)-positive patients undergoing chemotherapy or immunosuppressive therapy. Not only HBsAg-positive patients but also HBsAg-negative/antibody to hepatitis B core antigen (anti-HBc)-positive patients (resolved hepatitis B) have the risk of HBVr. The investigator's studies have demonstrated that the risk of HBsAg seroreversion was 10% in diffuse large B cell lymphoma patients undergoing anti-CD20 (rituximab) treatment; and the risk of HBsAg reverse seroconversion in rheumatic arthritis (RA) patients with resolved HBV infection and received biological disease-modifying antirheumatic drugs (bDMARDs) or glucocorticoid (GC) treatment can persist for up to 10 years. In the investigator's previous study, it also be investigated the risk of HBVr under different immunosuppressant regimens in HBsAg-positive patients with RA, and the investigator pointed out immunosuppressive treatment with a combination of GC, synthetic disease-modifying antirheumatic drugs (sDMARDs), and bDMARDs has the highest risk of HBVr with annual incidence around 20%. Recent studies also reported that the risk of HBVr associated with TNF-α inhibitor treatment widely ranged from 12.3% to 62.5%.
Antiviral prophylaxis by nucleos(t)ide analogues (NUCs) is recommended for patients with high risk of HBVr according to 2018 AASLD guidance. Phase 3 studies reported that tenofovir alafenamide (Vemlidy, TAF) can effectively suppress HBV in both HBeAg-positive and HBeAg-negative chronic hepatitis B patients, and TAF is superior to TDF in safety profiles and ALT normalization. However, the evidence of TAF in prevention HBV reactivation for patients with HBsAg-positive and imflammatory arthritis, who need bDMARDs are still missing. Therefore, the investigator plans to conduct this randomized controlled trial to confirm the efficacy of TAF as a prophylactic antiviral agent for HBsAg-positive patients with inflammatory arthritis (IA) on bDMARDs treatment.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Patients who fulfilled in all inclusion and exclusion criteria will be randomized into TAF 25mg qd or observation arm in 1:1 ratio. * 54 patients will be randomized into TAF arm*. * 54 patients will be randomized into observation arm initially.
| Arm | Type | Receives |
|---|---|---|
| TAF arm | Experimental | Drug: Tenofovir alafenamide54 patients will be randomized into TAF arm*. TAF 25 mg QD will be initiated 7 days before bDMARDs, and continued for up to 144-weeks. *for patients received rituximab (anti-CD20 monoclonal antibody) will be enrolled into TAF arm, and TAF 25 mg QD will be initiated 7 days before rituximab, and continued for up to 144-weeks. Max 20 rituximab patients will be recruited. |
| Observation arm | Other | Drug: Tenofovir alafenamide54 patients will be randomized into observation arm initially. These patients will be closely monitored their HBV status (including qHBsAg and HBV DNA) for 48 weeks. TAF 25 mg QD will be initiated for 144 weeks in the presence of HBV reactivation, or after 48 weeks of observation. |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age >=20 years old;
- History of chronic hepatitis B with HBsAg-positive;
- Both HBeAg-positive and HBeAg-negative are allowed;
- Inflammatory arthritis (including psoriatic arthritis);
- On bDMARDs treatment or will start bDMARDs within in 4 weeks. The bDMARDs included all anti-TNF-α agents, rituximab (anti-CD20 monoclonal antibody), tocilizumab (anti-interleukin 6 receptor monoclonal antibody), abatacept (cytotoxic T-lymphocyte-associated antigen 4 immunoglobulin), and all new biologics with indication of IA treatment;
Key exclusion criteria (6 listed)
- Child-Pugh class >B7;
- Active EV bleeding within 4 weeks;
- History of hepatic encephalopathy or intractable ascites;
- Coexist with other primary liver diseases, such as active chronic hepatitis C, hepatitis D, autoimmune hepatitis, or Wilson's disease. (*HCV RNA undetectable is allowed to enroll);
- Active malignancy;
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 |
|---|---|---|
| Tenofovir alafenamideAlso: Vemlidy, TAFTenofovir alafenamide (TAF, brand name: Vemlidy) is a hepatitis B virus nucleotide reverse transcriptase inhibitor oral medication for the treatment of chronic hepatitis B virus infection. It is a prodrug of tenofovir. Closely related to the commonly used reverse-transcriptase inhibitor tenofovir disoproxil fumarate, TAF has greater antiviral activity and better distribution into lymphoid tissues than that agent. Vemlidy was approved by the U.S. Food and Drug Administration (FDA) in November 2016 and the TAIWAN Food and Drug Administration (TFDA) in April 2017. | Drug | Observation arm, TAF arm |
Primary outcome
1-year HBV reactivation rate
Time frame: Up to 1-year
The assessment for the HBV reactivation is by the marker as hepatitis b viral load (unit: IU/ML).
5 secondary outcomes
Serial change of renal and liver function
Time frame: Up to 3-years
Observation of bone mineral density at 48-weeks, 96-weeks, and 144-weeks
Time frame: Up to 3-years
The 1-year virological remission rate
Time frame: Up to 1-year
The 1-year HBeAg seroconversion rate
Time frame: Up to 1-year
The adverse reactions and compliance
Time frame: Up to 3-years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2021.
- 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.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Tenofovir alafenamide in people with HBV and Inflammatory Arthritis, run by Taipei Veterans General Hospital, Taiwan.
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 9 inclusion and 6 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 12 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
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 Yi-Hsaing Huang, M.D. Ph.D. (+886-2-28757506, yhhuang@vghtpe.gov.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
1-year HBV reactivation rate (time frame: Up to 1-year). 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 12 Aug 2021.