Shield Therapeutics PLC, London, UK.
Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.
Nephrol Dial Transplant. 2021 Jul 23;36(8):1399-1407. doi: 10.1093/ndt/gfaa116.
Hyperphosphataemia is a common complication of chronic kidney disease (CKD). PT20 (ferric iron oxide adipate) is an investigational molecule engineered to offer enhanced phosphate-binding properties relative to other phosphate binders.
In this double-blind, parallel-group, placebo-controlled, dose-ranging study (ClinicalTrials.gov identifier NCT02151643), the efficacy and safety of 28 days of oral PT20 treatment were evaluated in patients with dialysis-dependent CKD. Participants were randomly assigned in an 8:8:8:13:13 ratio to receive PT20 (400, 800, 1600 or 3200 mg) or placebo three times daily.
Among 153 participants, 129 completed treatment [7 discontinued because of adverse events (AEs), 2 because of hyperphosphataemia and 15 for other reasons]. PT20 treatment for 28 days resulted in a statistically significant and dose-dependent reduction in serum phosphate concentration. There were no statistically significant effects of PT20 treatment on changes in haemoglobin or ferritin concentrations or transferrin saturation between Days 1 and 29. The incidence of treatment-emergent AEs was broadly similar across the PT20 and placebo groups (42-59% versus 44%). The most common PT20 treatment-related AEs were gastrointestinal, primarily diarrhoea (13-18%) and discoloured faeces (3-23%). No serious AEs were considered to be related to study treatment. There were no clinically significant changes in laboratory results reflecting acid/base status or increases in ferritin that could indicate the absorption of components of PT20.
In this first study investigating the efficacy and safety of PT20 in patients with hyperphosphataemia and dialysis-dependent CKD, PT20 significantly lowered serum phosphate concentrations and was generally well tolerated.
高磷血症是慢性肾脏病（CKD）的常见并发症。PT20（氧化铁己二酸酯）是一种经过工程设计的研究性分子，与其他磷酸盐结合剂相比，具有增强的磷酸盐结合特性。
在这项双盲、平行组、安慰剂对照、剂量范围研究（ClinicalTrials.gov 标识符 NCT02151643）中，评估了 28 天口服 PT20 治疗对依赖透析的 CKD 患者的疗效和安全性。参与者按照 8:8:8:13:13 的比例随机分配，接受 PT20（400、800、1600 或 3200mg）或安慰剂，每日三次。
在 153 名参与者中，129 名完成了治疗[7 名因不良反应（AE）而停药，2 名因高磷血症，15 名因其他原因]。PT20 治疗 28 天可显著降低血清磷酸盐浓度，且呈剂量依赖性。PT20 治疗对第 1 天至第 29 天期间血红蛋白或铁蛋白浓度或转铁蛋白饱和度的变化无统计学显著影响。PT20 组和安慰剂组治疗中出现的不良事件发生率相似（42-59% vs 44%）。最常见的与 PT20 治疗相关的 AE 是胃肠道，主要是腹泻（13-18%）和粪便变色（3-23%）。没有认为与研究治疗相关的严重 AE。实验室结果无临床意义的变化，反映酸碱状态或铁蛋白增加，这可能表明 PT20 成分的吸收。
在这项首次研究中，PT20 治疗高磷血症和依赖透析的 CKD 患者的疗效和安全性，PT20 显著降低血清磷酸盐浓度，且一般耐受性良好。
