Switching From TDF to TAF vs. Maintaining TDF in Chronic Hepatitis B With Resistance to Adefovir or Entecavir.
Status:
Completed
Trial end date:
2021-03-25
Target enrollment:
Participant gender:
Summary
Treatment of CHB patients with genotypic resistance to NUCs has been problematic due to the
lack of data from randomized trials. Recently, two randomized trials comparing the efficacy
of TDF monotherapy versus TDF and ETV combination therapy in CHB patients with documented
genotypic resistance to adefovir (ADV) or ETV demonstrated TDF monotherapy was not
statistically different in viral suppression at week 48 of treatment.1,2 The extension study
based on the above two trials merged study subjects from these trials with changing from TDF
and ETV combination group to TDF monotherapy to evaluate long-term efficacy and safety of TDF
monotherapy for multidrug-resistant patients. At the time of merging of 192 subjects, by
intention-to-treat analysis, 66.3% of TDF group and 68.0% of TDF-ETV group had virological
response as determined by serum HBV DNA <15 IU/mL. (in press) Three year long-term follow up
study showed that the proportion of virologic suppression increased to 76.8% and 72.2% in
TDF-TDF and TDF/TDF-ETV groups, respectively( P=0.46). (in press)
TAF, a novel prodrug of tenofovir was developed to have greater stability in plasma than TDF,
thereby enabling more efficient delivery of the active metabolite to target cells at a
substantially lower dose. The reduced systemic exposure of tenofovir offers the potential for
an improved safety profile compared to TDF a benefit that demonstrated in a recent clinical
trial in patients with HIV infection. In a recent double-blind randomized phase 3
noninferiority trial with 873 treatment naive patients who were positive for HBeAg, the
proportion of patients receiving TAF who had HBV DNA <29 IU/mL at week 48 was 64%, which was
non-inferior to the rate of 67% in patients receiving TDF (P=0.25).3 In the safety profile,
TAF group had significantly smaller decrease in BMD than TDF group in the hip and spine, as
well as significantly smaller increases in serum creatinine at week 48.3 For treatment naive
HBeAg negative patients, a recent study with 425 subjects applied the same methodology and
showed noninferiority in efficacy of TAF compared to TDF at week 48.4 Considering
noninferiority in efficacy and superior bone and renal safety from TAF, TAF might be
considered preferred choice of NUC instead of TDF. However, it is still unknown whether TAF
would show similar efficacy and safety profile in patients with multidrug-resistant CHB.
Phase:
Phase 4
Details
Lead Sponsor:
Young-Suk Lim
Collaborators:
Konkuk University Medical Center Korea University Guro Hospital Samsung Medical Center Seoul National University Hospital