In a randomized, double-blind, placebo-controlled, multicenter, 52-week phase 3 clinical trial (NCT05115942), 270 mg of hydronidone (Gyre Therapeutics) per day is expected to have positive benefits when used for the treatment of liver fibrosis related to chronic hepatitis B (CHB), according to study investigators.1,2 This theory is supported by prior phase 2 clinical trial evidence in which hydronidone with entecavir (Baraclude; Bristol-Myers Squibb) resulted in significant reversal of liver fibrosis.1-3
About the Trials
Phase 2 Trial
- Trial Name: A Phase II Clinical Trial of Hydronidone Capsules(F351) in Patients With Liver Fibrosis Induced by HBV Chronic Hepatitis (HBV)
- ClinicalTrials.gov ID: NCT02499562
- Sponsor: Shanghai Genomics, Inc.
- Completion Date: November 20, 2020
Phase 3 Trial
- Trial Name: Hydronidone for the Treatment of Liver Fibrosis Associated with Chronic Viral Hepatitis B Phase 3 Trial.
- ClinicalTrials.gov ID: NCT05115942
- Sponsor: Beijing Continent Pharmaceutical Co, Ltd.
- Completion Date: October 22, 2024
Hepatitis B virus infection, which is the leading cause of hepatocellular carcinoma and cirrhosis in Asia Pacific, is also likely to lead to liver fibrosis. At the time of this study being published3, pirfenidone was FDA-approved for the treatment of idiopathic pulmonary fibrosis. Hydronidone is a novel structural modification of pirfenidone with the specific aim of reducing hepatotoxicity. The investigators aimed to assess the safety and efficacy of hydronidone in patients with CHB-associated liver fibrosis.3
The multicenter, randomized, double-blind, placebo-controlled, 52-week phase 2 trial (NCT02499562)4 enrolled 168 patients who were randomly assigned to receive either 180 mg (n = 42), 270 mg (n = 42), or 360 mg of oral hydronidine (n = 41) per day, or placebo (n = 43). All participants also received 0.5 mg of entecavir per day. The trial’s primary end point was defined as fibrosis improvement, which was the reduction of at least 1 Ishak score at week 52 of treatment.3
The fibrosis improvement end point was achieved by 11 patients (25.6%) in the placebo group and 17 patients (40.5%) in the 180-mg (P = .12), 23 patients (54.8%) in the 270-mg (P = .006), and 18 patients (43.9%) in the 360-mg (P = .08) groups. Notably, the improvement rate was 58 of 125 (46.4%) in the combined hydronidone group (P = .014). The investigators observed similar overall safety profiles and incidences of serious adverse events among the groups.3
With these clinically significant histological improvements of liver fibrosis in patients with CHB, a phase 3 trial was initiated to confirm these findings. Specifically, because 270 mg of hydronidone appeared to show the best efficacy of fibrosis regression when administered with entecavir3, this dose was selected for the trial’s 52-week duration.1,2
The phase 3 clinical study was conducted at 44 study centers across China. Adult patients aged 18 to 65 years with significant liver fibrosis (defined as an Ishak score ≥3 on liver biopsy) associated with CHB were enrolled in the trial. The study consisted of a 28-day screening period and a 52-week treatment period, followed by an extension study or additional follow-up. The study’s primary end point was the efficacy of fibrosis reversal (defined as a decrease in the Ishak stage score of liver fibrosis by ≥1) after 52 weeks of treatment, compared with baseline.1
A total of 248 patients with CHB-associated liver fibrosis were enrolled, with 124 patients in both the hydronidone group and the control group. Following randomization, patients in the treatment group received 3 hydronidone capsules 3 times a day 30 minutes before meals—adding to 270 mg—for 52 weeks. Patients in the control group received placebo capsules administered at the same schedule. Like the phase 2 trial, both groups also received 0.5 mg of entecavir once per day as baseline treatment for 52 weeks. On-site visits occurred at weeks 0, 4, 8, 12, 24, 36, and 52, with additional follow-up visits as necessary.1
Given the positive findings of the 270-mg dose in the phase 2 trial, the investigators expressed their confidence that similar benefits will be observed in the phase 3 assessment. Though the previous phase 2 trial showed that some patients still had progression of liver fibrosis even after antiviral treatment, explained the authors, they anticipate fewer patients will experience fibrosis or cirrhosis progression, and a significant number will show reversal of fibrosis with hydronidone.1
REFERENCES
1. Cai X, Qu Y, Xie W, Wang Y, Zhao M, Zhang L, et al. Hydronidone for the Treatment of Liver Fibrosis Associated with Chronic Hepatitis B: Protocol for a Phase 3 Randomized Trial. J Clin Transl Hepatol. Published online: Mar 10, 2025. doi:10.14218/JCTH.2024.00472.
2. Hydronidone for the Treatment of Liver Fibrosis Associated with Chronic Viral Hepatitis B Phase 3 Trial. ClinicalTrials.gov identifier: NCT05115942. Updated December 20, 2024. Accessed April 22, 2025. https://clinicaltrials.gov/study/NCT05115942
3. Cai X, Liu X, Xie W, et al. Hydronidone for the Treatment of Liver Fibrosis Related to Chronic Hepatitis B: A Phase 2 Randomized Controlled Trial. Clin Gastroenterol Hepatol. 2023;21(7):1893-1901.e7. doi:10.1016/j.cgh.2022.05.056
4. A Phase II Clinical Trial of Hydronidone Capsules(F351) in Patients With Liver Fibrosis Induced by HBV Chronic Hepatitis (HBV). ClinicalTrials.gov identifier: NCT02499562. Updated June 23, 2022. Accessed April 22, 2025. https://clinicaltrials.gov/study/NCT02499562
