Pradefovir Treatment in Patients with Chronic Hepatitis B: Week 24 Results from a Multicenter, Double-blind, Randomized, Noninferiority, Phase 2 Trial.

Objectives Pradefovir is a liver-targeted prodrug of adefovir, a nucleotide analog with antiviral activity against hepatitis B virus (HBV) DNA polymerase. This phase 2 study compared the efficacy and safety of oral pradefovir (30mg, 45mg, 60mg, and 75mg) versus tenofovir disoproxil fumarate (TDF; 300mg) 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 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 30mg, 45mg, 60mg, and 75mg, respectively, compared to 5.12 log10 IU/ml with TDF. However, HBeAg loss was attained by more participants who received 45mg, 60mg or 75mg pradefovir than those receiving TDF (12%, 6%, 9% vs. 3%). The TDF group exhibited a more significant increase in serum creatinine than the pradefovir 30mg or 45mg groups, and serum phosphate levels were comparable among all groups. Most adverse events were mild (grade 1). No treatment-related severe adverse events were reported. Overall, adverse events and laboratory abnormalities were comparable to the TDF group. Conclusions Pradefovir exhibited comparable reductions in HBV DNA levels to TDF. All treatments were safe and well tolerated.