Pradefovir Treatment in Patients With Chronic Hepatitis B: Week 24 Results From a Multicenter, Double-Blind, Randomized, Noninferiority, Phase 2 Trial

Clin Infect Dis. 2022 Jun 10;74(11):1925-1932. doi: 10.1093/cid/ciab763.

Abstract

Background: Pradefovir is a liver-targeted prodrug of adefovir, a nucleoside/nucleotide analogue with antiviral activity against hepatitis B virus (HBV) DNA polymerase. This phase 2 study compared the efficacy and safety of oral pradefovir (30, 45, 60, or 75 mg) versus tenofovir disoproxil fumarate (TDF; 300 mg) and aimed to identify the most appropriate dose of pradefovir for the forthcoming phase 3 study.

Methods: Treatment-naive and experienced (not on treatment >6 months) patients with chronic hepatitis B were eligible.

Results: A total of 240 participants were randomized and treated in the study (48 per group). Approximately 80% were hepatitis B e antigen (HBeAg) positive, and 10% had liver cirrhosis. The reductions from baseline in HBV DNA levels achieved at week 24 were 5.40, 5.34, 5.33, and 5.40 log10 IU/mL, with pradefovir doses of 30-, 45-, 60-, and 75-mg, respectively, compared with 5.12 log10 IU/mL with TDF. However, HBeAg loss was attained by more participants who received 45-, 60-, or 75-mg pradefovir than by those receiving TDF (12%, 6%, and 9% vs 3%). The TDF group exhibited a more significant increase in serum creatinine than the pradefovir 30- and 45-mg groups, and serum phosphate levels were comparable among all groups. Most adverse events (AEs) were mild (grade 1). No treatment-related severe AEs were reported. Overall, AEs and laboratory abnormalities were comparable to those in the TDF group.

Conclusions: Pradefovir and TDF exhibited comparable reductions in HBV DNA levels. All treatments were safe and well tolerated.

Clinical trials registration: NCT00230503 and China Drug Trials CTR2018042.

Keywords: efficacy; hepatitis B; pradefovir; safety; tenofovir disoproxil fumarate.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives
  • Antiviral Agents / adverse effects
  • DNA, Viral
  • Hepatitis B e Antigens
  • Hepatitis B virus / genetics
  • Hepatitis B, Chronic*
  • Humans
  • Organophosphorus Compounds
  • Prodrugs* / adverse effects
  • Tenofovir / adverse effects
  • Treatment Outcome
  • Viral Load

Substances

  • Antiviral Agents
  • DNA, Viral
  • Hepatitis B e Antigens
  • Organophosphorus Compounds
  • Prodrugs
  • Tenofovir
  • pradefovir
  • Adenine

Associated data

  • ClinicalTrials.gov/NCT00230503