Clinical trial NCT03559790: Treatment Efficacy and Safety of TDF-TAF Switch Study in South Korea
Official title: 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
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Chronic Hepatitis b
Keywords: chronic hepatitis B
tenofovir alafenamide
tenofovir disoproxil fumarate
Safety
Efficacy
Lead sponsor: The Catholic University of Korea
Sponsor class: OTHER
First posted: 2018-06-18
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Population that receive TDF-TAF switch therapy

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Complete Virological response
timeFrame: at Week 96.
measure: Incidence of of elevation of serum creatinine as a measure of renal safety
timeFrame: at Week 96
measure: Incidence of osteopenia and osteoporosis as a measure of bone safety
timeFrame: at Week 96
Secondary outcomes:
measure: Biochemical response
timeFrame: at Week 48 and 96
measure: Serologic response
timeFrame: at Week 48 and 96
measure: Serologic response
timeFrame: at Week 48 and 96
measure: Incidence of treatment-emergent adverse events
timeFrame: at Week 48 and 96
Other outcomes:
Locations:
city: Junggu
country: Korea, Republic of
facility: The Catholic University of Korea, Daejeon St.Mary's Hosptial
state: Daejeon
Study officials:
affiliation: Daejeon St. Mary's hospital
name: Myeong Jun Song
role: PRINCIPAL_INVESTIGATOR
References: