Abstract: TH-PO1147
A Phase 3 Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Enarodustat for the Treatment of Renal Anemia in Chinese Non-Dialysis CKD Patients
Session Information
- Late-Breaking Posters
November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials
Authors
- Yu, Xueqing, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China
- Ye, Zhiming, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China
- Liang, Xinling, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China
- Zhang, Yanning, General Hospital of Northern Theater Command, Shenyang, Liaoning, China
- Hu, Weiping, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China
- Chen, Xiaonong, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China
- Guan, Tianjun, Zhongshan Hospital Xiamen University, Xiamen, Fujian, China
- Zhou, Hua, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
- Fu, Ping, West China Hospital of Sichuan University, Chengdu, Sichuan, China
- Liao, Yunhua, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
- Xu, Hui, Xiangya Hospital Central South University, Changsha, Hunan, China
- Yang, Aicheng, Jiangmen Wuyi Traditional Chinese Medicine Hospital, Jiangmen, China
- Zhao, Hongwen, Third Military Medical University Southwest Hospital Department of Nephrology, Chongqing, Chongqing, China
- Yang, Lili, Shenzhen Salubris Pharmaceuticals Co Ltd, Shenzhen, Guangdong, China
- Sun, Yujie, Shenzhen Salubris Pharmaceuticals Co Ltd, Shenzhen, Guangdong, China
- Xiao, Yongzhen, Shenzhen Salubris Pharmaceuticals Co Ltd, Shenzhen, Guangdong, China
Background
Enarodustat (ENA) is a novel Hypoxia-inducible factor-prolyl hydroxylase inhibitor indicated for treating anemia in chronic kidney disease (CKD) patients. This phase 3 trial was conducted to establish the efficacy and safety of ENA in Chinese non-dialysis CKD (ND-CKD) patients.
Methods
This was a randomized, phase 3, double-blind, placebo-controlled, extended open-label, multicenter clinical study (NCT06016036). It consisted of a 4-week screening period, 8-week double-blind period (DBP), 16-week open-label period (OLP), and a 2-week safety follow-up period. Patients in the investigational drug group received once-daily ENA tablets at an initial dose of 4 mg/d for week1-5, then were adjusted in the range of 1/2/4/6/8 mg/d for every 4 weeks based on Hb levels and its changes. The primary endpoint was the change in Hb levels from baseline (week1) averaged over week7–9. Secondary endpoints included Hb levels, its changes and proportion of the iron therapy, etc. Exploratory endpoints included iron parameters, etc.
Results
In total, 156 patients which had not received erythropoiesis-stimulating agents (ESA) treatment for ≥8 weeks were randomized in a 2:1 ratio to receive ENA (n=103) or placebo (PLA, n=53). In DBP, the change of Hb from baseline (mean±SD) averaged over week7–9 was 15.99±9.46g/L vs 0.14±8.08 g/L in ENA and PLA group (P<0.001). The mean Hb increase in the first 4 weeks was 11.82±9.56g/L vs 1.58±7.56g/L, the difference(LSM±SE) was 10.23 ±1.55 g/L (P<0.001). 85.3% vs 30% (P<0.001) of patients achieved a Hb level of ≥100g/L averaged over week7–9. In ENA group, the cumulative proportion of iron therapy decreased from 45.6% at baseline to 13.4% during the OLP, and the mean hepcidin levels decreased 57.7% (P<0.0001) from baseline at week9. Regarding the safety results, the incidences of adverse events (77.7% vs 79.2%) and adverse drug reactions (18.4% vs 15.1%) in ENA and PLA group were similar. There were no significant clinical changes in lipid parameters in ENA group.
Conclusion
Enarodustat was more effective in treating anemia in ESA-Naïve Chinese ND-CKD patients than placebo. Meanwhile, it had a similar safety profile with the placebo.