Switching From Tenofovir Disoproxi Fumarate to Tenofovir Alafenamide in Chronic Hepatitis B Patients With Antiviral Resistance

• Conditions: Hepatitis B; Antiviral Drug Adverse Reaction
• Interventions: Drug: Tenofovir disoproxil fumarate 300mg; Drug: Tenofovir Alafenamide 25 mg

• Registration Number: NCT03566030
• Lead Sponsor: Yonsei University

Brief Summary

* To evaluate the efficacy of switching to tenofovir alafenamide (TAF) 25 mg QD versus continued tenofovir disoproxil fumarate (TDF) 300 mg QD in CHB patients with antiviral resistance, as determined by the proportion of virologically suppressed patients at week 48

* To evaluate the safety and tolerability of switching to TAF 25 mg QD versus continuing TDF 300 mg QD in antiviral-resistant subjects with chronic HBV at week 48

Detailed Description

The investigators will conduct a multicenter observational study to evaluate the safety and efficacy of TAF 25 mg QD in chronic hepatitis B patients with antiviral resistance who switch from TDF to TAF. The safety and antiviral activity will be assessed as a part of routine medical care. Subjects will be obtained from an existing cohort of patients treated with a TDF-based regimen due to antiviral resistance, which has been supported by Gilead (IN-US-174-1255).

It is anticipated that approximately 300 CHB patients with antiviral resistance taking TDF 300 mg QD will be enrolled in this study. All consecutive patients will be allocated to receive either TAF 25 mg QD or TDF 300 mg QD (possibly 50% vs. 50%, the proportion of patients enrolled in the study is an estimate based on the clinical experience.), according to the decision of the individual patients and their physicians, with informed consent. Patients are switched independently based on physicians discretion/decision prior to study enrollment, and the study protocol would NOT have any influence over the process.

All consecutive patients will be prospectively monitored every 6 months during the first year and thereafter every 6 months up to 3 years. At each visit, a routine examination and determination of biochemical and virological parameters (HBV DNA level, HBeAg, anti-HBe, HBsAg \[quantitatively, if available\], and anti-HBs) will be performed. Lab tests and markers will be routinely monitored every 6 months.

Recruitment method: In this study, we plan to use an existing cohort of patients treated with a TDF-based regimen due to antiviral resistance (IN-US-174-1255). Data on all consecutive patients currently receiving TDF due to antiviral resistance at enrollment will be followed up prospectively every 3-6 months for 2 years. The patients will be recruited consecutively. Patients will be recruited only after the treatment decision has been made. No aspect of this study will interfere with or influence routine medical practice.

Number of study sites: At least seven representative institutes in South Korea. Target population: Korean adult subjects with CHB receiving TDF due to antiviral resistance.

Study Timeline

• Study First Submitted: 2018-05-22
• Status Verified: 2018-06
• Study First Submitted QC: 2018-06-11
• Last Update Submitted: 2018-06-11
• Study First Posted: 2018-06-21
• Last Update Posted: 2018-06-21
• Study Start: 2018-09-01
• Primary Completion: 2019-08-31
• Study Completion: 2020-08-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

• Must have the ability to understand and sign a written informed consent form; consent must be obtained prior to initiation of study procedures
• Adult male and non-pregnant, non-lactating female subjects, ≥20 years of age based on the date of the screening visit.
• Documented evidence of chronic HBV infection previously
• TDF monotherapy, TDF-based combination therapy, or switching to TAF at least 4 weeks prior to screening in virologically suppressed chronic hepatitis B patients with multi-antiviral resistance
• Must be willing and able to comply with all study requirements

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Exclusion Criteria

• Co-infection with HCV, HDV, HIV

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Tenofovir Disoproxil Fumarate 300 mg QD	Tenofovir disoproxil fumarate 300mg	Administered Tenofovir Disoproxil Fumarate 300 mg QD
Tenofovir Alafenamide	Tenofovir Alafenamide 25 mg	Administered Tenofovir Alafenamide 25 mg QD

Primary Outcome Measures

Name	Time	Method
Serum HBV DNA level	at week 48	The proportion of subjects who achieve a sustained serum HBV DNA level \< 20 IU/mL (undetectable serum HBV DNA by PCR)

Secondary Outcome Measures

Name	Time	Method
Serum creatinine & PO4 level	at 24, 48, 72, and 96 week	The change in serum creatinine \& PO4 from baseline
Serum HBV DNA level	at week 96	The proportion of subjects who achieve a sustained serum HBV DNA level \< 20 IU/mL (undetectable serum HBV DNA by PCR)
Serum eGFR	at 24, 48, 72, and 96 week	The change in serum eGFR (Cockcroft-Gault method) from baseline
Hip and spine BMD	at 48, 96 week	The percent change in hip and spine BMD from baseline