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

Real-life Data of Switching From Tenofovir Disoproxi Fumarate (TDF) to Tenofovir Alafenamide (TAF) in Virologically Suppressed Chronic Hepatitis B Patients With Antiviral Resistance

• 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

Study Overview

• Status: Unknown
• Conditions: Hepatitis B; Antiviral Drug Adverse Reaction
• Intervention / Treatment: Drug: Tenofovir disoproxil fumarate 300mg; Drug: Tenofovir Alafenamide 25 mg

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 Type: Observational
• Enrollment (Anticipated): 300

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

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. 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).

Description

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

Exclusion Criteria:

• Co-infection with HCV, HDV, HIV

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Tenofovir Disoproxil Fumarate 300 mg QD; Administered Tenofovir Disoproxil Fumarate 300 mg QD	Drug: Tenofovir disoproxil fumarate 300mg; Administered Tenofovir disoproxil fumarate 300 mg QD; Other Names: TDF
Tenofovir Alafenamide; Administered Tenofovir Alafenamide 25 mg QD	Drug: Tenofovir Alafenamide 25 mg; Administered Tenofovir Alafenamide 25 mg QD; Other Names: TAF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum HBV DNA level	The proportion of subjects who achieve a sustained serum HBV DNA level < 20 IU/mL (undetectable serum HBV DNA by PCR)	at week 48

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Yonsei University

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2018
• Primary Completion (Anticipated): August 31, 2019
• Study Completion (Anticipated): August 31, 2020

Study Registration Dates

• First Submitted: May 22, 2018
• First Submitted That Met QC Criteria: June 11, 2018
• First Posted (Actual): June 21, 2018

Study Record Updates

• Last Update Posted (Actual): June 21, 2018
• Last Update Submitted That Met QC Criteria: June 11, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: Tenofovir Alafenamide; Hepatitis B; Tenofovir Disoproxil Fumarate; Switch
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Drug-Related Side Effects and Adverse Reactions; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir
• Other Study ID Numbers: IN-US-320-4406

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No