Treatment Efficacy and Safety of TDF-TAF Switch Study in South Korea

Treatment Efficacy and Safety of Tenofovir Alafenamide (TAF) Switch Therapy in Patients Who Have Been Treated With Tenofovir Disoproxil Fumarate (TDF) in naïve Chronic Hepatitis B: a Real Life Multicenter Cohort Study in Korea

Recent TAF has introduced to have more safe profiles than TDF in clinical trials. Especially, TDF has the renal safety issue in high risk group including HIV, decompensated cirrhosis (ascites), uncontrolled DM etc.

However, there is no available cohort data for treatment efficacy and safety in TDF-TAF switch therapy in treatment-naïve chronic hepatitis B.

The aim of this study is to evaluate safety and efficacy of TAF switch therapy in patients with chronic hepatitis B who have been treated with TDF.

Study Overview

• Status: Unknown
• Conditions: Chronic Hepatitis b
• Intervention / Treatment: Drug: tenofovir alafenamide

• Study Type: Observational
• Enrollment (Anticipated): 400

Contacts and Locations

Study Locations

• Korea, Republic of
  • Daejeon
    • Junggu, Daejeon, Korea, Republic of
      • Recruiting
      • The Catholic University of Korea, Daejeon St.Mary's Hosptial
      • Contact: Myeong Jun Song; Phone Number: 8242-220-9291

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Population that receive TDF-TAF switch therapy

Description

Inclusion Criteria:

1. Must have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures.
2. Adult male and non-pregnant, non-lactating female subjects, 18 years of age and older, based on the date of the screening visit. A negative serum pregnancy test at Screening is required for female subjects of childbearing potential (unless surgically sterile or greater than 2 years post-menopausal).
3. Documented evidence of chronic HBV infection (e.g. HBsAg positive for more than 6 months)

4. Previous TDF naïve treatment (more than 96 weeks) baseline status including chronic hepatitis B with the following:

   • HBeAg-positive and HBeAb negative at Screening
   • Screening HBV DNA ≥ 1x 105 copies/mL
   • Screening serum ALT level ≥2×ULN(80 IU/L) and ≤ 10 ×ULN (by center laboratory range) OR
   • HBeAg-negative and HBeAb positive at Screening
   • Screening HBV DNA ≥ 1x 104 copies/mL
   • Screening serum ALT level ≥2×ULN(80 IU/L) and ≤ 10 ×ULN (by center laboratory range) OR
   • Cirrhosis at Screening

   • Screening HBV DNA ≥ 1x 104 copies/mL regardless of HBeAg status

     • Treatment naïve subjects defined as no history of antiviral therapy or < 12 weeks of oral antiviral treatment with any nucleoside or nucleotide analogue, including lamivudine or adefovir, clevudine, telbivudine, entecavir
5. The decision is made by the provider and patient to switch from TDF to TAF prior to discussion of the study of enrollment
6. Following the decision to switch therapy, signed written informed consent after being instructed about the objective and procedure of the clinical study
7. Must be willing and able to comply with all study requirements

Exclusion Criteria:

Subjects who meet any of the following exclusion criteria are not to be enrolled in the study.

1. Pregnant women, women who are breastfeeding or who believe they may wish to become pregnant during the course of the study.
2. Co-infection with HCV, HIV
3. Evidence of hepatocellular carcinoma (e.g. α-fetoprotein> 50 ng/mL or as evidenced by recent ultrasound or other standard of care measure)
4. Malignancy within 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection (basal cell skin cancer, etc). Subjects under evaluation for possible malignancy are not eligible
5. Current alcohol or substance abuse judged by the investigator to potentially interfere with subject compliance
6. Currently receiving therapy with cytotoxic agent, nephrotoxic agents, or agents capable of modifying renal excretion
7. Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with dosing requirements.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Virological response	Portion of subjects with plasma HBV DNA levels below 116 copies/mL	at Week 96.
Incidence of of elevation of serum creatinine as a measure of renal safety	Incidence of elevation of serum creatinine (>0.5mg/dL) from baseline creatinine	at Week 96
Incidence of osteopenia and osteoporosis as a measure of bone safety	Incidence of osteopenia and osteoporosis according to Bone Mineral Density	at Week 96

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biochemical response	ALT normalization (Male <30 IU/L, Female <19 IU/L)	at Week 48 and 96
Serologic response	loss rate of HBeAg in HBeAg positive patients	at Week 48 and 96
Serologic response	seroconversion rate in HBeAg positive patients	at Week 48 and 96
Incidence of treatment-emergent adverse events	all adverse events during tenofovir treatment	at Week 48 and 96

Collaborators and Investigators

• Sponsor: The Catholic University of Korea
• Investigators: Principal Investigator: Myeong Jun Song, Daejeon St. Mary's hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 18, 2018
• Primary Completion (Anticipated): August 1, 2020
• Study Completion (Anticipated): August 1, 2021

Study Registration Dates

• First Submitted: May 14, 2018
• First Submitted That Met QC Criteria: June 14, 2018
• First Posted (Actual): June 18, 2018

Study Record Updates

• Last Update Posted (Actual): January 30, 2019
• Last Update Submitted That Met QC Criteria: January 29, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Safety; Efficacy; tenofovir disoproxil fumarate; tenofovir alafenamide; chronic hepatitis B
• Additional Relevant MeSH Terms: 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 B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Hepatitis, Chronic; 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: Gilead IN-US-320-4407

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes