Kidney Week

Abstract: TH-PO134

SHR6508, a Calcium-Sensing Receptor Agonist, in Patients on Hemodialysis Who Have Secondary Hyperparathyroidism: A Phase 2 Trial

Session Information

• CKD-MBD: Clinical
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Bone and Mineral Metabolism

• 502 Bone and Mineral Metabolism: Clinical

Authors

• Yu, Xueqing, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China

Xueqing Yu, MD, PhD

• Ye, Zhiming, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China

Zhiming Ye

• Fan, Li, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China

Li Fan, MD

• Chen, Yuqing, Peking University First Hospital, Beijing, Beijing, China

Yuqing Chen, MD

• Wang, Pei, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China

Pei Wang, MD

• Yan, Rui, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China

Rui Yan, MD

• Liu, Bin, Wuxi People's Hospital, Wuxi, Jiangsu, China

Bin Liu, MD

• Wei, Yong, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, China

Yong Wei, PhD

• Ye, Hong, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China

Hong Ye, MD

• Gao, Bi hu, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China

Bi hu Gao, MD

• Zhang, Xin, Jiangsu Hengrui Pharmaceuticals Co Ltd, Shanghai, Shanghai, China

Xin Zhang, MMSc

• Yang, Xinyu, Jiangsu Hengrui Pharmaceuticals Co Ltd, Shanghai, Shanghai, China

Xinyu Yang, MS

• Yang, Xue, Jiangsu Hengrui Pharmaceuticals Co Ltd, Shanghai, Shanghai, China

Xue Yang, MPH

Background

Secondary hyperparathyroidism (SHPT) is a common clinical manifestation among patients receiving hemodialysis (HD). SHR6508 is a calcimimetic developed to reduce parathyroid hormone (PTH) secretion in HD patients with SHPT. We aimed to evaluate the efficacy and safety of SHR6508 compared with cinacalcet in HD patients with SHPT.

Methods

This was a multicenter, randomized, open-label, active-controlled, dose titration phase 2 trial conducted in 34 sites in China. Adult patients who had received HD for at least 12 weeks and with intact PTH (iPTH) ≥400 pg/ml and serum corrected calcium (cCa) ≥2.25 mmol/L were recruited. Eligible patients were randomized in a 2:2:1 ratio to SHR6508 Group 1 (slow titration), SHR6508 Group 2 (rapid titration), and cinacalcet group, stratified by the baseline iPTH level (<700 or ≥700 pg/mL). Patients in SHR6508 Group 1 and 2 received SHR6508 2.5-20 mg by intravenous injection after HD section for 16 weeks, and those in cinacalcet group received oral cinacalcet 25-100 mg once daily for 16 weeks, with the dosage adjusted based on iPTH and cCa levels. The primary outcome was percentage change in iPTH from baseline to week 16.

Results

A total of 75 HD patients were randomized (n=30 for SHR6508 Group 1 and 2, respectively; n=15 for cinacalcet). iPTH significantly declined in patients treated with SHR6508 than those treated with cinacalcet during treatment period (Figure 1). The percentage changes in mean iPTH from baseline to week 16 were -62.7%, -61.7% and -38.9% in SHR6508 Group 1, Group 2 and cinacalcet group, respectively (P<0.05). The treatment-related adverse events (TRAEs) were comparable among three groups (83.3% vs 83.3% vs 86.7%) and all SHR6508-related TRAEs were mild or moderate. Nausea (3.3% vs 3.3% vs 6.7%) and vomiting (0 vs 0 vs 13.3%) were less common in patients treated with SHR6508.

Conclusion

SHR6508 showed greater efficacy in iPTH reduction and similar safety profiles compared to cinacalcet in HD patients with SHPT.

Funding

• Commercial Support – Jiangsu Hengrui Pharmaceuticals Co., Ltd