Center for Kidney Disease, Second Affiliated Hospital, Nanjing Medical University, Nanjing, China.
Department of Nephrology, Peking University People's Hospital, Beijing, China.
Nephrol Dial Transplant. 2024 Sep 27;39(10):1649-1661. doi: 10.1093/ndt/gfae053.
VS-505 (AP301), an acacia and ferric oxyhydroxide polymer, is a novel fiber-iron-based phosphate binder. This two-part Phase 2 study evaluated the tolerability, safety and efficacy of oral VS-505 administered three times daily with meals in treating hyperphosphatemia in chronic kidney disease (CKD) patients receiving maintenance hemodialysis (MHD).
In Part 1, patients received dose-escalated treatment with VS-505 2.25, 4.50 and 9.00 g/day for 2 weeks each, guided by serum phosphorus levels. In Part 2, patients received randomized, open-label, fixed-dosage treatment with VS-505 (1.50, 2.25, 4.50 or 6.75 g/day) or sevelamer carbonate 4.80 g/day for 6 weeks. The primary efficacy endpoint was the change in serum phosphorus.
The study enrolled 158 patients (Part 1: 25; Part 2: 133), with 130 exposed to VS-505 in total. VS-505 was well tolerated. The most common adverse events were gastrointestinal disorders, mainly feces discolored (56%) and diarrhea (15%; generally during Weeks 1-2 of treatment). Most gastrointestinal disorders resolved without intervention, and none was serious. In Part 1, serum phosphorus significantly improved (mean change -2.0 mg/dL; 95% confidence interval -2.7, -1.4) after VS-505 dose escalation. In Part 2, serum phosphorus significantly and dose-dependently improved in all VS-505 arms, with clinically meaningful reductions with VS-505 4.50 and 6.75 g/day, and sevelamer carbonate 4.80 g/day [mean change -1.6 (-2.2, -1.0), -1.8 (-2.4, -1.2) and -1.4 (-2.2, -0.5) mg/dL, respectively]. In both parts, serum phosphorus reductions occurred within 1 week of VS-505 initiation, returning to baseline within 2 weeks of VS-505 discontinuation.
VS-505, a novel phosphate binder, was well tolerated with a manageable safety profile, and effectively and dose-dependently reduced serum phosphorus in CKD patients with hyperphosphatemia receiving MHD.
NCT04551300 .
VS-505（AP301）是一种新型的纤维铁基聚磷酸盐结合剂，由金合欢树和三价铁羟氧化物聚合物组成。这项两部分的 2 期研究评估了口服 VS-505 每日三次与餐同服治疗接受维持性血液透析（MHD）的慢性肾脏病（CKD）患者高磷血症的耐受性、安全性和疗效。
在第 1 部分中，患者接受了剂量递增治疗，VS-505 的剂量分别为 2.25、4.50 和 9.00g/天，持续 2 周，根据血清磷水平进行指导。在第 2 部分中，患者接受了随机、开放标签、固定剂量治疗，VS-505 的剂量分别为 1.50、2.25、4.50 或 6.75g/天，或司维拉姆碳酸 4.80g/天，持续 6 周。主要疗效终点是血清磷的变化。
该研究共纳入了 158 名患者（第 1 部分：25 名；第 2 部分：133 名），其中共有 130 名患者接受了 VS-505 治疗。VS-505 具有良好的耐受性。最常见的不良反应是胃肠道疾病，主要是粪便变色（56%）和腹泻（15%；通常在治疗的第 1-2 周）。大多数胃肠道疾病无需干预即可自行缓解，且均不严重。在第 1 部分中，VS-505 剂量递增后，血清磷显著改善（平均变化-2.0mg/dL；95%置信区间-2.7，-1.4）。在第 2 部分中，所有 VS-505 治疗组的血清磷均显著且剂量依赖性改善，VS-505 4.50 和 6.75g/天以及司维拉姆碳酸 4.80g/天治疗组的血清磷显著降低[平均变化-1.6（-2.2，-1.0）、-1.8（-2.4，-1.2）和-1.4（-2.2，-0.5）mg/dL]。在两部分研究中，VS-505 治疗后 1 周内血清磷开始降低，2 周内恢复至基线水平。
VS-505 是一种新型的磷酸盐结合剂，具有良好的耐受性和可管理的安全性，可有效且剂量依赖性地降低接受 MHD 的高磷血症 CKD 患者的血清磷水平。
NCT04551300。
