The Efficacy of Prophylactic TAF for HBsAg-positive Patients Receiving bDMARDs

HBV Clinical Trial

Official title:

The Efficacy of TAF as a Prophylactic Antiviral Agent for HBsAg-positive Patients Receiving Biological DMARDs (bDMARDs)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05001672
• Other study ID #: IN-TW-320-6150
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: August 15, 2021
• Est. completion date: December 31, 2025

Study information

• Verified date: August 2021
• Source: Taipei Veterans General Hospital, Taiwan
• Contact: Yi-Hsaing Huang, M.D. Ph.D.
• Phone: +886-2-28757506
• Email: yhhuang[@]vghtpe.gov.tw
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 108
• Est. completion date: December 31, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

• 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-a 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;
• No limitation of the baseline HBV DNA level;
• Total bilirubin level <2 mg/dL;
• ALT < 2x ULN (<80 U/L).

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Arthritis
• HBV
• Inflammatory Arthritis

Intervention

Drug:
• Tenofovir alafenamide
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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Taipei Veterans General Hospital, Taiwan

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	1-year HBV reactivation rate	The assessment for the HBV reactivation is by the marker as hepatitis b viral load (unit: IU/ML).	Up to 1-year
Secondary	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.	Up to 3-years
Secondary	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.	Up to 3-years
Secondary	The 1-year virological remission rate	The assessment for the HBV reactivation is by the marker as hepatitis b viral load (unit: IU/ML).	Up to 1-year
Secondary	The 1-year HBeAg seroconversion rate	The assessment for the HBeAg seroconversion is by the marker as HBeAg (unit: COI).	Up to 1-year
Secondary	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.	Up to 3-years