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

NCT05001672 | Unknown Phase 4

• 1 other identifier: IN-TW-320-6150
• Study Type: interventional
• Target: 108
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

HBV; Inflammatory Arthritis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Serial change of renal and liver function

  Up to 3-years

• Observation of bone mineral density at 48-weeks, 96-weeks, and 144-weeks

  Up to 3-years

• The 1-year virological remission rate

  Up to 1-year

• The 1-year HBeAg seroconversion rate

  Up to 1-year

• The adverse reactions and compliance

  Up to 3-years

Study Arms (2)

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.

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.

Drug: Tenofovir alafenamide

Interventions

Tenofovir alafenamide DRUG

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.

Also known as: Vemlidy, TAF

Observation arm; TAF arm

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Taipei Veterans General Hospital, Taiwan: lead

MeSH Terms

Conditions

Arthritis

Interventions

tenofovir alafenamide

Condition Hierarchy (Ancestors)

Joint Diseases; Musculoskeletal Diseases

Central Study Contacts

Yi-Hsaing Huang, M.D. Ph.D.

CONTACT

+886-2-28757506; yhhuang@vghtpe.gov.tw

Chieh-Ju Lee, Master

CONTACT

+886-939859265; ssbugi@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 2, 2021
• First Posted: August 12, 2021
• Study Start: August 15, 2021
• Primary Completion: June 30, 2025
• Study Completion: December 31, 2025
• Last Updated: August 12, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share