Chronic Hepatitis B virus symbol.
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A multicenter Phase 3 clinical trial is underway to evaluate the efficacy of hydronidone, a novel antifibrotic agent, in reversing liver fibrosis among patients with chronic hepatitis B (CHB). The study, conducted across 44 centers in China, investigates whether a 270 mg/day dose of hydronidone, when added to standard antiviral therapy with entecavir, can significantly reduce fibrosis severity after 52 weeks of treatment. The primary endpoint is a ≥1-point improvement in liver fibrosis, as measured by the Ishak staging system. Adult participants between the ages of 18 and 65 with biopsy-confirmed moderate to severe fibrosis (Ishak score ≥3) were randomized in a double-blind, placebo-controlled design.1
Investigtaors elaborate, “Our previous Phase 2 study demonstrated promising results regarding the antifibrotic effect of hydronidone with acceptable safety. The results showed that the fibrosis improvement endpoint was achieved by 11 patients (25.6%) in the placebo group and by 58 of 125 patients (46.4%) in the hydronidone group.”1
What You Need To Know
A Phase 3 trial is evaluating hydronidone, a novel antifibrotic agent, for its ability to reverse liver fibrosis in patients with CHB when added to standard antiviral therapy.
The trial’s primary endpoint is a ≥1-point improvement in liver fibrosis, with hydronidone showing promising results in a previous Phase 2 study that demonstrated significant fibrosis reversal.
The study recognizes limitations, including the small sample size in Phase 2 and potential biopsy scoring variability, but aims to provide robust evidence supporting hydronidone’s antifibrotic effects in a larger, more diverse patient population.
Additional details from the Phase 2 trial include that, at eight centers in China, 168 patients with biopsy-confirmed CHB-related fibrosis were randomized to receive daily entecavir plus either placebo or hydronidone at doses of 180 mg, 270 mg, or 360 mg. After 52 weeks of treatment, 46.4 percent of patients in the combined hydronidone arms achieved at least a one-point improvement in Ishak fibrosis score compared with 25.6 percent in the placebo group. The 270 mg dose demonstrated the greatest efficacy, with 54.8 percent of patients achieving fibrosis regression (P = .006). The safety profile was comparable across all treatment groups, with no significant increase in serious adverse events. These Phase 2 findings support hydronidone as a promising antifibrotic therapy for CHB-related liver fibrosis.2
The study acknowledges two key limitations: the small sample size of approximately 40 patients per group in the Phase 2 trial, which warrants cautious interpretation of the results, and potential variability in liver biopsy scoring, which will be addressed by having an expert team of three independent pathologists independently evaluate the fibrosis scores to ensure reliability.1
Moving forward, investigators state, “We anticipate that this Phase 3 trial will provide robust evidence of the antifibrotic effect of hydronidone based on cause-control treatment. The previous Phase 2 trial showed that some patients still had progression of liver fibrosis even after antiviral treatment. We also anticipate fewer patients will experience fibrosis or cirrhosis progression, while a significant number will show reversal of fibrosis with hydronidone.”1
As there are currently no approved drugs specifically indicated for the treatment of liver fibrosis, this trial could represent a significant advancement in addressing a major unmet need in chronic liver disease management. If successful, hydronidone may become the first targeted therapy for CHB-related fibrosis, offering a potential new treatment option for patients at risk of progressing to cirrhosis or liver failure.
