Double-Blind, Randomized, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Ilofotase Alfa in Patients at Risk for Renal Damage Following Open Heart Surgery

The aim of this clinical trial is to evaluate the efficacy and safety of two intravenous administrations of ilofotase alfa in patients at risk for renal damage following open heart surgery.

开始日期2023-12-19

申办/合作机构

AM-Pharma BV

[+1]

NCT05890794

/ Completed临床1/2期

Open-Label Pilot Trial to Evaluate the Effects of Ilofotase Alfa on Biomarkers in Adult Patients With Hypophosphatasia

The goal of this clinical trial is to compare the effectiveness of two doses of ilofotase alfa, an enzyme replacement treatment, in patients with hypophosphatasia (HPP). The main question it aims to answer is if the harmful accumulating levels of extracellular inorganic pyrophosphate (PPi) and pyridoxal 5'-phosphate (PLP) can be reduced with ilofotase alfa.
Researchers will compare the two doses of ilofotase alfa to see if treatment effects differ between the doses.

开始日期2023-05-15

申办/合作机构

AM-Pharma BV

NCT04411472

/ Terminated临床3期

A DB, Placebo-Controlled, Two-Arm Parallel-Group, Phase 3 RCT to Investigate the Efficacy and Safety of Recombinant Human Alkaline Phosphatase for Treatment of Patients With SA-AKI

Clinical phase 3 study to investigate the effect of recAP on 28 day mortality in patients admitted to the ICU with acute kidney injury that is caused by sepsis.
The study has three distinct SA-AKI trial populations:
1. The main trial population: Patients with a pre-AKI reference eGFR ≥45 mL/min/1.73 m2 and no proven or suspected SARS-CoV-2 at time of randomization.
2. A 'moderate' CKD population: Patients with a pre-AKI reference eGFR ≥25 and <45 mL/min/1.73 m2 and no proven or suspected SARS-CoV-2 at time of randomization.
3. A Corona Virus Disease 2019 (COVID-19) population: Patients with proven or suspected SARS-CoV-2 at time of randomization with or without 'moderate' CKD. For patients in this population, COVID-19 should be the main cause of SA-AKI.
In the main study population approximately 1400 patients will be enrolled and in the two cohorts with moderate CKD and COVID-19 each up to 100 patients.
There are two arms in the study, one with active treatment and one with an inactive compound (placebo). Treatment is by 1 hour intravenous infusion, for three days. Patients are followed up for 28 days to see if there is an improvement on mortality, and followed for 90 and 180 days for mortality and other outcomes e.g. long-term kidney function and quality of life.

开始日期2020-11-02

申办/合作机构

AM-Pharma Holding BV

100 项与 Ilofotase alfa 相关的临床结果

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100 项与 Ilofotase alfa 相关的转化医学

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100 项与 Ilofotase alfa 相关的专利（医药）

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项与 Ilofotase alfa 相关的文献（医药）

2026-03-02·JOURNAL OF BONE AND MINERAL RESEARCH

A randomized Phase 1b trial evaluating the pharmacodynamics of ilofotase alfa in adults with hypophosphatasia

Article

作者: Rutsch, Frank ; Seefried, Lothar ; Kleinert, Sina ; Genest, Franca ; Mallek, Markus ; Kraan, Maarten ; Nitschke, Yvonne ; Bernholz, Juliane

Abstract:

Hypophosphatasia is a rare genetic disease caused by deficient alkaline phosphatase (AP) activity. In adults, this causes functional limitations, substantial disability with pain and reduced quality of life. This Phase 1b, single-center, open-label trial investigated ilofotase alfa, a fully human recombinant protein intended as enzyme replacement therapy, in adults with hypophosphatasia. Changes in plasma levels of AP substrates inorganic pyrophosphate and pyridoxal-5′-phosphate were evaluated. Participants were randomized 1:1 to receive at 0.8 or 3.2 mg/kg ilofotase alfa intravenously over 1 h. Twelve participants were enrolled and completed the trial. At baseline, all participants had reduced AP activity and elevated pyridoxal-5′-phosphate. The greatest reduction in inorganic pyrophosphate and pyridoxal-5′-phosphate occurred 2 h after start of dosing in both treatment groups. Across the 10-d follow-up period, inorganic pyrophosphate values returned to baseline levels more rapidly in the 0.8 mg/kg group compared with the 3.2 mg/kg group. Mean circulating AP activity peaked 24 h after dosing and subsequently declined but remained above the lower limit of normal throughout the study. A dose-proportional increase in ilofotase alfa was observed, reaching peak concentration 1-h post-infusion. Eight treatment-emergent adverse events occurred, all classified as mild. These data demonstrate that single-dose ilofotase alfa enhances AP activity and results in dose-dependent reductions in primary disease-specific biomarkers without undesired effects on mineral homeostasis.Clinical trial registration number: ClinicalTrials.gov number: NCT05890794.

2024-11-01·BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

recAP administration ameliorates sepsis outcomes through modulation of gut and liver inflammation

Article

作者: Strutz, Andrew G ; Macom, Rhiannon V ; Brown, Candice M ; Lewellyn, Kennedi Z

Sepsis, broadly described as a systemic infection, is one of the leading causes of death and long-term disability worldwide. There are limited therapeutic options available that either improve survival and/or improve the quality of life in survivors. Ilofotase alfa, also known as recombinant alkaline phosphatase (recAP), has been associated with reduced mortality in a subset of patients with sepsis-associated acute kidney injury. However, whether recAP exhibits any therapeutic benefits in other organ systems beyond the kidney is less clear. The objective of this study was to evaluate the effects of recAP on survival, behavior, and intestinal inflammation in a mouse model of sepsis, cecal ligation and puncture (CLP). Following CLP, either recAP or saline vehicle was administered via daily intraperitoneal injections to determine its treatment efficacy from early through late sepsis. We found that administration of recAP suppressed indices of inflammation in the gut and liver but did not improve survival or behavioral outcomes. These results demonstrate that recAP's therapeutic efficacy in the gut and liver may provide a valuable treatment to improve long-term outcomes in sepsis survivors.

2024-10-01·Trauma case reports

Monoclonal antibody anti-sclerostin for treatment of pelvic insufficiency fractures in adult hypophosphatasia: A case report

Article

作者: Dessain, Alicia ; Schwab, Pierre-Emmanuel ; Milby, Joshua

Hypophosphatasia is a rare inherited metabolic disease leading to inhibition of bone and teeth mineralization that can be complicated by multiple insufficiency fractures. Treatment is currently limited to enzyme replacement therapy using bone-targeting recombinant human alkaline phosphatase, or asfotase alfa. Romosozumab is a monoclonal anti-sclerostin antibody originally indicated for the treatment of osteoporosis in postmenopausal women with high-risk of fracture. Recently its indication had been expanded to other metabolic bone disorders such as osteogenesis imperfecta. We report a unique case of a 67-yer-old female with hypophosphatasia complicated by multiple delayed-union and nonunion insufficiency fractures of the pelvis. After 12-month therapy with Romosozumab to address her osteoporosis, the patient healed her fractures and increased her bone mass density. Our case report shows interesting effects of Romozumab in an adult patient with hypophosphatasia. It not only helped increase bone density, but also help in the healing process of delayed-union and nonunion insufficiency fractures of the pelvis and prevented the occurrence of new fractures during the treatment period. To our knowledge, this is the first report describing the potential effect of Romosozumab on insufficiency fractures in patients with hypophosphatasia.

项与 Ilofotase alfa 相关的新闻（医药）

2026-04-21

·Intensive Care Medicine

治疗急性肾损伤的新药

治疗急性肾损伤的新药 New drugs for acute kidney injury Citation: Hariri G, Legrand M. New drugs for acute kidney injury. J Intensive Med. 2024;5(1):3–11. doi: 10.1016/j.jointm.2024.08.001. 核心结论急性肾损伤（AKI）在重症及围术期患者中发病率高达30%-60%，目前仍无高级别证据支持的预防或治疗药物。本文系统综述了基于最新病理生理机制（炎症应答、代谢重编程、血流动力学调节、补体活化及细胞凋亡/修复）的在研新药，涵盖碱性磷酸酶、Reltecimod、血管紧张素II、维生素B3类、CD39重组蛋白、Ravulizumab、siRNA QPI-1002及间充质干细胞等。多项II/III期临床试验正在评估其疗效，为降低AKI发生率及严重程度带来新希望。正文急性肾损伤（AKI）是全球性健康问题，每年影响超过1300万人，并导致约170万例死亡[1]。从病理生理角度看，AKI以肾小球滤过率（GFR）快速下降为特征，数小时或数日内表现为血清肌酐急剧升高。2004年之前由于缺乏统一定义，AKI的诊断标准从轻度肌酐升高至需要肾脏替代治疗（RRT）范围广泛[2]。RIFLE、AKIN及KDIGO分级系统的建立，依据血清肌酐和尿量变化提供了结构化诊疗路径，实现了早期识别与干预[3-5]。在重症监护环境中，AKI发病率异质性较大（15%-60%），且与死亡率升高、住院时间延长及慢性肾脏病（CKD）风险增加密切相关[6-8]。尽管过去二十年危重症患者管理取得显著进步，但预防或治疗AKI的有效药物干预仍十分缺乏。近期对AKI病理生理机制的深入理解揭示了炎症、代谢紊乱及细胞修复障碍等共同通路，为新型药物研发提供了方向（图1，表1）。图1：重症及围术期急性肾损伤预防或治疗新药的作用机制概览。HGF: 肝细胞生长因子；MSC: 间充质干细胞。基于上述机制，目前处于研发阶段的药物涵盖了免疫调节、血流动力学优化、细胞能量代谢支持、补体抑制及抗凋亡/促修复等多个维度。下文按照靶点分类逐一阐述代表性药物的临床证据。1. 炎症调控碱性磷酸酶（ALP）可通过去磷酸化脂多糖（LPS）及胞外ATP/ADP，减轻Toll样受体介导的先天免疫反应。STOP-AKI试验（n=301）中，重组ALP（ilofotase alfa）虽未改善7天肾功能，但28天肌酐清除率提升18.5 mL/min（95%CI: 5.3-31.7），死亡率降低（14.4% vs 26.7%）[18]。然而后续III期REVIVAL试验（n=655）未显示28天全因死亡率获益，但MAKE90复合终点（56.7% vs 64.6%, P=0.02）提示可能降低RRT需求[19]。针对CSA-AKI的II期预防试验（NCT06168799）正在进行。 Reltecimod是一种靶向T细胞表面CD28的肽类，可调节脓毒症免疫应答。在坏死性软组织感染III期试验中虽未达到主要复合终点，但第14天SOFA评分改善（65.1% vs 52.6%, P=0.04）[24]。目前针对KDIGO 2-3期AKI合并腹腔脓毒症的III期试验（NCT03403751）正在评估28天AKI恢复率。活性维生素D（骨化三醇）可通过下调核因子κB减轻炎症。但ACTIVATE-AKI试验（NCT02962102）未显示7天内死亡或RRT需求的显著差异。RBT-1（锡原卟啉+蔗糖铁）通过上调HO-1、铁蛋白发挥预适应保护，PROTECT III期研究（n=400）正在进行，主要终点为死亡、透析需求、ICU住院日及30天再入院复合指标。 TIN816（重组CD39）可水解胞外ATP/ADP，抑制炎症及血小板聚集。针对SA-AKI的II期试验（NCT05996835）以第1-8天时间校正肌酐清除率曲线下面积为主要终点；CSA-AKI预防试验（NCT05524051）计划纳入120例患者。2. 血流动力学调节血管紧张素II选择性收缩肾出球小动脉，提升GFR。ATHOS-3试验显示，血管紧张素II显著提高顽固性血管扩张性休克患者3小时平均动脉压（69.9% vs 23.4%, OR=7.95）[46]，且在需RRT的亚组中28天生存率更高（53% vs 30%）[47]。预防CSA-AKI的可行性研究提示AKI发生率降低（25% vs 38%, P=0.31），III期试验（NCT05199493）正在开展。血管加压素：心脏术后血管麻痹性休克患者中，血管加压素较去甲肾上腺素显著降低CSA-AKI（10.3% vs 35.8%, P<0.0001）[52]；但在脓毒性休克中未显示AKI预防获益。个体患者数据Meta分析提示可能降低RRT需求（RR=0.86）。两项RCT（NCT04602767, NCT06125184）将进一步明确。左西孟旦：钙增敏剂兼有入球小动脉扩张作用。心脏手术Meta分析显示可减少CSA-AKI（OR=0.51）及RRT（OR=0.43），但大型RCT未证实获益[57]。LEVO-AKI试验（NCT02531724）正在评估已发生CSA-AKI的治疗效果。3. 细胞代谢与线粒体功能维生素B3类（烟酰胺、烟酰胺核糖）通过补充NAD+保护肾小管。心脏手术II期试验显示烟酰胺使AKI发生率降低35%[59]。多项RCT正在验证其预防CSA-AKI（NCT04750616）、肾移植后移植物功能（NCT05513807）及脓毒性休克相关AKI（NCT04589546）的疗效。ASP1128（PPARδ调节剂）在心脏手术高危患者中未减少AKI发生率（24.6% vs 21%, P=0.595）[62]。SIRT1激活剂NRPT（烟酰胺核糖+紫檀芪）II期试验（NCT04342975）正在主动脉弓置换患者中评估预防效果。表1：重症及围术期急性肾损伤预防/治疗新药汇总药物机制靶点相关临床试验研究人群 Angiotensin II 血流动力学肾出球小动脉 NCT05199493 预防CSA-AKI Angiotensin II 血流动力学肾出球小动脉 NCT04592744 肝移植后AKI预防 Angiotensin II 血流动力学肾出球小动脉 NCT04901169 肝移植后AKI预防 Vasopressin 血流动力学 V1a受体 NCT04602767 预防CSA-AKI Vasopressin 血流动力学 V1a受体 NCT06125184 预防SA-AKI(脓毒性休克) Levosimendan 血流动力学/正性肌力肾入球小动脉 NCT02531724 CSA-AKI治疗 Reltecimod 免疫调节 CD28 NCT03403751 SA-AKI(腹腔脓毒症) Activated vitamin D 免疫调节 NF-κB NCT02962102 高危患者AKI预防 ALP (Ilofotase alfa) 免疫调节 TLR-4/LPS NCT06168799 预防CSA-AKI RBT-1 缺血预适应 HO-1/铁蛋白 PROTECT study 预防CSA-AKI TIN816 ATP/ADP水解 CD39 NCT05996835 SA-AKI TIN816 ATP/ADP水解 CD39 NCT05524051 预防CSA-AKI Vitamin B3 (Nicotinamide) 细胞代谢 NAD+合成 NCT04750616 预防CSA-AKI Nicotinamide 细胞代谢 NAD+ NCT05513807 肾移植后移植物功能延迟 NR (Nicotinamide riboside) NAD+前体 SIRT1 NCT04818216 COVID-19相关AKI ASP1128 PPARδ激动剂脂肪酸氧化 II期(已停止) CSA-AKI高危 NRPT (NR+Pterostilbene) SIRT1激活 NAD+/SIRT1 NCT04342975 主动脉弓置换后AKI预防 Ravulizumab 补体C5抑制剂 C5 NCT05746559 预防CSA-AKI siRNA QPI-1002 抗凋亡 p53 NCT02610296 肾移植后移植物功能延迟 HGF-mimetic (BB3) 细胞修复/抗凋亡 cMet/Bcl-2 NCT02771509 预防CSA-AKI Mesenchymal Stem Cells 免疫调节/修复多靶点 NCT04445220 COVID-19合并RRT Umbilical cord MSC 组织修复多靶点 NCT04194671 AKI治疗补体抑制剂Ravulizumab（长效C5单抗）在COVID-19相关AKI的小样本试验中显示透析需求降低（P=0.03），III期ARTEMIS试验（NCT05746559）正在心脏手术CKD患者中验证其预防CSA-AKI的效果。4. 凋亡抑制与细胞修复 siRNA药物QPI-1002（靶向p53）在心脏手术高危患者中使AKI发生率降低13%（37% vs 50%, P=0.02）[75]，但MAKE90无差异；III期预防试验因无效而终止。HGF模拟物BB3在肾移植后未改善360天eGFR（P=0.32）[80]，GUARD试验（NCT02771509）正在评估其对CSA-AKI的预防效果。间充质干细胞（MSC）在CSA-AKI的II期试验中未显示获益，但体外扩增MSC可能具有免疫修复潜力，相关试验仍在进行（NCT04445220, NCT04194671）。综上所述，目前尚无获批的AKI特效药，但基于精准病理生理靶点的多种药物已进入后期临床试验阶段，为改善重症及手术患者AKI结局带来了切实希望。参考文献 Mehta R.L., Cerdá J., Burdmann E.A., Tonelli M., García-García G., Jha V., et al. International Society of Nephrology's 0by25 initiative for acute kidney injury (zero preventable deaths by 2025): a human rights case for nephrology. Lancet. 2015;385:2616–2643. doi: 10.1016/S0140-6736(15)60126-X. Ricci Z., Cruz D.N., Ronco C. Classification and staging of acute kidney injury: beyond the RIFLE and AKIN criteria. Nat Rev Nephrol. 2011;7(4):201–208. doi: 10.1038/nrneph.2011.14. Bellomo R., Ronco C., Kellum J.A., Mehta R.L., Palevsky P. Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. 2004;8(4):R204–R212. doi: 10.1186/cc2872. Mehta R.L., Kellum J.A., Shah S.V., Molitoris B.A., Ronco C., Warnock D.G., et al. Acute kidney injury network: report of an initiative to improve outcomes in acute kidney injury. Crit Care. 2007;11(2):R31. doi: 10.1186/cc5713. 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Effect of human recombinant alkaline phosphatase on 7-day creatinine clearance in patients with sepsis-associated acute kidney injury: a randomized clinical trial. JAMA. 2018;320(19):1998–2009. doi: 10.1001/jama.2018.14283. Pickkers P., Angus D.C., Bass K., Bellomo R., van den Berg E., Bernholz J., et al. Phase-3 trial of recombinant human alkaline phosphatase for patients with sepsis-associated acute kidney injury (REVIVAL) Intens Care Med. 2024;50(1):68–78. doi: 10.1007/s00134-023-07271-w. Ramachandran S., Subramanian V., Mohanakumar T. Immune responses to self-antigens (autoimmunity) in allograft rejection. Clin Transpl. 2012:261–272. Ramachandran G., Kaempfer R., Chung C.S., Shirvan A., Chahin A.B., Palardy J.E., et al. CD28 homodimer interface mimetic peptide acts as a preventive and therapeutic agent in models of severe bacterial sepsis and gram-negative bacterial peritonitis. J Infect Dis. 2015;211(6):995–1003. doi: 10.1093/infdis/jiu556. Edgar R., Tarrio M.L., Maislin G., Chiguang F., Kaempfer R., Cross A., et al. Treatment with one dose of Reltecimod is superior to two doses in mouse models of lethal infection. Int J Pept Res Ther. 2020;26:1669–1683. doi: 10.1007/s10989-019-09974-5. Bulger E.M., Maier R.V., Sperry J., Joshi M., Henry S., Moore F.A., et al. A novel drug for treatment of necrotizing soft-tissue infections: a randomized clinical trial. JAMA Surg. 2014;149(6):528–536. doi: 10.1001/jamasurg.2013.4841. Bulger E.M., May A.K., Robinson B., Evans D.C., Henry S., Green J.M., et al. A novel immune modulator for patients with necrotizing soft tissue infections (NSTI): results of a multicenter, phase 3 randomized controlled trial of reltecimod (AB 103) Ann Surg. 2020;272(3):469–478. doi: 10.1097/SLA.0000000000004102. Keung L., Perwad F. Vitamin D and kidney disease. Bone Rep. 2018;9:93–100. doi: 10.1016/j.bonr.2018.07.002. Al-Badr W., Martin K.J. Vitamin D and kidney disease. Clin J Am Soc Nephrol. 2008;3(5):1555–1560. doi: 10.2215/CJN.01150308. Graidis S., Papavramidis T.S., Papaioannou M. Vitamin D and acute kidney injury: a two-way causality relation and a predictive, prognostic, and therapeutic role of vitamin D. Front Nutr. 2021;7 doi: 10.3389/fnut.2020.630951. Xu S., Chen Y.H., Tan Z.X., Xie D.D., Zhang C., Zhang Z.H., et al. Vitamin D3 pretreatment regulates renal inflammatory responses during lipopolysaccharide-induced acute kidney injury. Sci Rep. 2015;5:18687. doi: 10.1038/srep18687. Vervloet M.G., Hsu S., de Boer I.H. Vitamin D supplementation in people with chronic kidney disease. Kidney Int. 2023;104(4):698–706. doi: 10.1016/j.kint.2023.07.010. Zhang H., Jiang Y., Shi N., Lu Y.Q. Serum vitamin D levels and acute kidney injury: a systemic review and meta-analysis. Sci Rep. 2022;12(1):20365. doi: 10.1038/s41598-022-24560-4. Leaf D.E., Jacob K.A., Srivastava A., Chen M.E., Christov M., Jüppner H., et al. Fibroblast growth factor 23 levels associate with AKI and death in critical illness. J Am Soc Nephrol. 2017;28(6):1877–1885. doi: 10.1681/ASN.2016080836. Eltzschig H.K., Eckle T. Ischemia and reperfusion–from mechanism to translation. Nat Med. 2011;17(11):1391–1401. doi: 10.1038/nm.2507. Huang Y., Rabb H., Womer K.L. Ischemia-reperfusion and immediate T cell responses. Cell Immunol. 2007;248(1):4–11. doi: 10.1016/j.cellimm.2007.03.009. Li C., Jackson R.M. Reactive species mechanisms of cellular hypoxia-reoxygenation injury. Am J Physiol Cell Physiol. 2002;282(2):C227–C241. doi: 10.1152/ajpcell.00112.2001. Zhang M., Liu Q., Meng H., Duan H., Liu X., Wu J., et al. Ischemia-reperfusion injury: molecular mechanisms and therapeutic targets. Signal Transduct Target Ther. 2024;9(1):12. doi: 10.1038/s41392-023-01688-x. Lamy A., Chertow G.M., Jessen M., Collar A., Brown C.D., Mack C.A., et al. Effects of RBT-1 on preconditioning response biomarkers in patients undergoing coronary artery bypass graft or heart valve surgery: a multicentre, double-blind, randomised, placebo-controlled phase 2 trial. EClinicalMedicine. 2024;68 doi: 10.1016/j.eclinm.2023.102364. Priyan V. Renibus begins subject dosing in phase III trial of RBT-1. Clinical Trials Arena. 2023 Cauwels A., Rogge E., Vandendriessche B., Shiva S., Brouckaert P. Extracellular ATP drives systemic inflammation, tissue damage and mortality. Cell Death Dis. 2014;5(3):e1102. doi: 10.1038/cddis.2014.70. Woulfe D., Yang J., Brass L. ADP and platelets: the end of the beginning. J Clin Invest. 2001;107:1503–1505. doi: 10.1172/JCI13361. Eltzschig H.K., Köhler D., Eckle T., Kong T., Robson S.C., Colgan S.P. Central role of Sp1-regulated CD39 in hypoxia/ischemia protection. Blood. 2009;113(1):224–232. doi: 10.1182/blood-2008-06-165746. Hayes G.M., Cairns B., Levashova Z., Chinn L., Perez M., Theunissen J.W., et al. CD39 is a promising therapeutic antibody target for the treatment of soft tissue sarcoma. Am J Transl Res. 2015;7(6):1181–1188. Granja T., Körner A., Glück C., Hohmann J.D., Wang X., Köhler D., et al. Targeting CD39 toward activated platelets reduces systemic inflammation and improves survival in sepsis: a preclinical pilot study. Crit Care Med. 2019;47(5) doi: 10.1097/CCM.0000000000003682. e420-420e427. Bellomo R., Forni L.G., Busse L.W., McCurdy M.T., Ham K.R., Boldt D.W., et al. Renin and survival in patients given angiotensin II for catecholamine-resistant vasodilatory shock. A clinical trial. Am J Respir Crit Care Med. 2020;202(9):1253–1261. doi: 10.1164/rccm.201911-2172OC. Küllmar M., Saadat-Gilani K., Weiss R., Massoth C., Lagan A., Cortés M.N., et al. Kinetic changes of plasma renin concentrations predict acute kidney injury in cardiac surgery patients. Am J Respir Crit Care Med. 2021;203(9):1119–1126. doi: 10.1164/rccm.202005-2050OC. Chawla L.S., Busse L., Brasha-Mitchell E., Davison D., Honiq J., Alotaibi Z., et al. Intravenous angiotensin II for the treatment of high-output shock (ATHOS trial): a pilot study. Crit Care. 2014;18(5):534. doi: 10.1186/s13054-014-0534-9. Khanna A., English S.W., Wang X.S., Ham K., Tumlin J., Szerlip H., et al. Angiotensin II for the treatment of vasodilatory shock. N Engl J Med. 2017;377(5):419–430. doi: 10.1056/NEJMoa1704154. Tumlin J.A., Murugan R., Deane A.M., Ostermann M., Busse L.W., Ham K.R., et al. Outcomes in patients with vasodilatory shock and renal replacement therapy treated with intravenous angiotensin II. Crit Care Med. 2018;46(6):949–957. doi: 10.1097/CCM.0000000000003092. Bokoch M.P., Tran A.T., Brinson E.L., Marcus S.G., Reddy M., Sun E., et al. Angiotensin II in liver transplantation (AngLT-1): protocol of a randomised, double-blind, placebo-controlled trial. BMJ Open. 2023;13(11) doi: 10.1136/bmjopen-2023-078713. Coulson T.G., Miles L.F., Serpa Neto A., Pilcher D., Weinberg L., Landoni G., et al. A double-blind randomised feasibility trial of angiotensin-2 in cardiac surgery( Anaesthesia. 2022;77(9):999–1009. doi: 10.1111/anae.15802. Finley J.J., 4th, Konstam M.A., Udelson J.E. Arginine vasopressin antagonists for the treatment of heart failure and hyponatremia. Circulation. 2008;118(4):410–421. doi: 10.1161/CIRCULATIONAHA.108.765289. Okazaki N., Iguchi N., Evans R.G., Hood S.G., Bellomo R., May C.N., et al. Beneficial effects of vasopressin compared with norepinephrine on renal perfusion, oxygenation, and function in experimental septic acute kidney injury. Crit Care Med. 2020;48(10) doi: 10.1097/CCM.0000000000004511. e951-951e958. Hajjar L.A., Vincent J.L., Barbosa Gomes Galas F.R., Rhodes A., Landoni G., Osawa E.A., et al. Vasopressin versus norepinephrine in patients with vasoplegic shock after cardiac surgery: the VANCS randomized controlled trial. Anesthesiology. 2017;126(1):85–93. doi: 10.1097/ALN.0000000000001434. Gordon A.C., Mason A.J., Thirunavukkarasu N., Perkins G.D., Cecconi M., Cepkova M., et al. Effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock: the VANISH randomized clinical trial. JAMA. 2016;316(5):509–518. doi: 10.1001/jama.2016.10485. Hajjar L.A., Zambolim C., Belletti A., de Almeida J.P., Gordon A.C., Oliveira G., et al. Vasopressin versus norepinephrine for the management of septic shock in cancer patients: the VANCS II randomized clinical trial. Crit Care Med. 2019;47(12):1743–1750. doi: 10.1097/CCM.0000000000004023. Pan J., Yang Y.M., Zhu J.Y., Lu Y.Q. Multiorgan drug action of levosimendan in critical illnesses. Biomed Res Int. 2019;2019 doi: 10.1155/2019/9731467. Zhou C., Gong J., Chen D., Wang W., Liu M., Liu B. Levosimendan for prevention of acute kidney injury after cardiac surgery: a meta-analysis of randomized controlled trials. Am J Kidney Dis. 2016;67:408–416. doi: 10.1053/j.ajkd.2015.09.015. Landoni G., Lomivorotov V.V., Alvaro G., Lobreglio R., Pisano A., Guarracino F., et al. Levosimendan for hemodynamic support after cardiac surgery. N Engl J Med. 2017;376(21):2021–2031. doi: 10.1056/NEJMoa1616325. Gordon A.C., Perkins G.D., Singer M., McAuley D.F., Orme R.M., Santhakumaran S., et al. Levosimendan for the prevention of acute organ dysfunction in sepsis. N Engl J Med. 2016;375(17):1638–1648. doi: 10.1056/NEJMoa1609409. Poyan Mehr A., Tran M.T., Ralto K.M., Leaf D.E., Washco V., Messmer J., et al. De novo NAD(+) biosynthetic impairment in acute kidney injury in humans. Nat Med. 2018;24(9):1351–1359. doi: 10.1038/s41591-018-0138-z. Gao J., Gu Z. The role of peroxisome proliferator-activated receptors in kidney diseases. Front Pharmacol. 2022;13 doi: 10.3389/fphar.2022.832732. Taniuchi Y., van Till J.W.O., Wojtkowski T., Toyoshima J., Koibuchi A., Sargent B., et al. Single- and multiple-dose safety, tolerability, pharmacokinetics, and pharmacodynamics of ASP1128, a novel peroxisome proliferator-activated receptor δ modulator, in healthy participants. Clin Pharmacol Drug Dev. 2023;12:810–818. doi: 10.1002/cpdd.1236. van Till J.W.O., Nojima H., Kameoka C., Hayashi C., Sakatani T., Washburn T.B., et al. The effects of peroxisome proliferator-activated receptor-delta modulator ASP1128 in patients at risk for acute kidney injury following cardiac surgery. Kidney Int Rep. 2023;8:1407–1416. doi: 10.1016/j.ekir.2023.04.004. Guan Y., Wang S.R., Huang X.Z., Xie Q.H., Xu Y.Y., Shang D., et al. Nicotinamide mononucleotide, an NAD+ precursor, rescues age-associated susceptibility to AKI in a Sirtuin 1–dependent manner. J Am Soc Nephrol. 2017;28:2337–2352. doi: 10.1681/ASN.2016040385. Guan Y., Hao C.M. SIRT1 and kidney function. Kidney Dis (Basel) 2016;1:258–265. doi: 10.1159/000440967. Peasley K., Chiba T., Goetzman E., Sims-Lucas S. Sirtuins play critical and diverse roles in acute kidney injury. Pediatr Nephrol. 2021;36:3539–3546. doi: 10.1007/s00467-020-04866-z. Simic P., Vela Parada X.F., Parikh S.M., Dellinger R., Guarente L.P., Rhee E.P. Nicotinamide riboside with pterostilbene (NRPT) increases NAD+ in patients with acute kidney injury (AKI): a randomized, double-blind, placebo-controlled, stepwise safety study of escalating doses of NRPT in patients with AKI. BMC Nephrol. 2020;21:342. doi: 10.1186/s12882-020-02006-1. Fakhouri F., Schwotzer N., Golshayan D., Frémeaux-Bacchi V. The rational use of complement inhibitors in kidney diseases. Kidney Int Rep. 2022;7:1165–1178. doi: 10.1016/j.ekir.2022.02.021. Sheridan D., Yu Z.X., Zhang Y., Patel R., Sun F., Lasaro M.A., et al. Design and preclinical characterization of ALXN1210: a novel anti-C5 antibody with extended duration of action. PLoS ONE. 2018;13 doi: 10.1371/journal.pone.0195909. Memon A.A., Ahmed H., Li Y., Wongboonsin J., Hundert J., Benoit S., et al. A randomized control trial of ravulizumab for treatment of patients with COVID-19 infection and kidney injury. Kidney Int Rep. 2022;7:2714–2717. doi: 10.1016/j.ekir.2022.09.003. Olsen T.S., Olsen H.S., Hansen H.E. Tubular ultrastructure in acute renal failure in man: epithelial necrosis and regeneration. Virchows Arch A Pathol Anat Histopathol. 1985;406:75–89. doi: 10.1007/BF00710559. Sanz A.B., Sanchez-Niño M.D., Ramos A.M., Ortiz A. Regulated cell death pathways in kidney disease. Nat Rev Nephrol. 2023;19:281–299. doi: 10.1038/s41581-023-00694-0. Tang C., Ma Z., Zhu J., Liu Z., Liu Y., Liu Y., et al. P53 in kidney injury and repair: mechanism and therapeutic potentials. Pharmacol Ther. 2019;195:5–12. doi: 10.1016/j.pharmthera.2018.10.013. Wei Q., Dong G., Yang T., Megyesi J., Price P.M., Dong Z. Activation and involvement of p53 in cisplatin-induced nephrotoxicity. Am J Physiol Renal Physiol. 2007;293:F1282–F1291. doi: 10.1152/ajprenal.00230.2007. Peddi V.R., Ratner L., Cooper M., Gaber O., Feng S., Tso P., et al. Treatment with QPI-1002, a short interfering (SI) RNA for the prophylaxis of delayed graft function.: abstract# 2967. Transplantation. 2014;98:153. doi: 10.1097/00007890-201407151-00467. Thielmann M., Corteville D., Szabo G., Swaminathan M., Lamy A., Lehner L.J., et al. Teprasiran, a small interfering RNA, for the prevention of acute kidney injury in high-risk patients undergoing cardiac surgery: a randomized clinical study. Circulation. 2021;144:1133–1144. doi: 10.1161/CIRCULATIONAHA.120.053029. Kawaida K., Matsumoto K., Shimazu H., Nakamura T. Hepatocyte growth factor prevents acute renal failure and accelerates renal regeneration in mice. Proc Natl Acad Sci U S A. 1994;91:4357–4361. doi: 10.1073/pnas.91.10.4357. Zhou D., Tan R.J., Lin L., Zhou L., Liu Y. Activation of hepatocyte growth factor receptor, c-met, in renal tubules is required for renoprotection after acute kidney injury. Kidney Int. 2013;84:509–520. doi: 10.1038/ki.2013.102. Narayan P., Duan B., Jiang K., Li J., Paka L., Yamin M.A., et al. Late intervention with the small molecule BB3 mitigates postischemic kidney injury. Am J Physiol Renal Physiol. 2016;311:F352–F361. doi: 10.1152/ajprenal.00455.2015. Bromberg J.S., Weir M.R., Gaber A.O., Yamin M.A., Goldberg I.D., Mayne T.J., et al. Renal function improvement following ANG-3777 treatment in patients at high risk for delayed graft function after kidney transplantation. Transplantation. 2021;105:443–450. doi: 10.1097/TP.0000000000003255. Vincenti F., Bromberg J., Kim J., Faravardeh A., Leca N., Alperovich G., et al. The hepatocyte growth factor mimetic, ANG-3777, in kidney transplant recipients with delayed graft function: results from a randomized phase 3 trial. Am J Transplant. 2024 doi: 10.1016/j.ajt.2024.02.014. S1600-6135(24)00156-4. Ayad S., Neylan J.F., Mayne T.J., Gouveia D., Swaminathan M. Hepatocyte growth factor mimetic ANG-3777 for cardiac surgery-associated acute kidney injury. Kidney Int Rep. 2020;5(12):2325–2332. doi: 10.1016/j.ekir.2020.09.031. Allinson C.S., Pollock C.A., Chen X. Mesenchymal stem cells in the treatment of acute kidney injury (AKI), chronic kidney disease (CKD) and the AKI-to-CKD transition. Intgr Med Nephrol Androl. 2023;10:e00014. doi: 10.1097/IMNA-D-22-00014. Swaminathan M., Stafford-Smith M., Chertow G.M., Warnock D.G., Paragamian V., Brenner R.M., et al. Allogeneic mesenchymal stem cells for treatment of AKI after cardiac surgery. J Am Soc Nephrol. 2018;29:260–267. doi: 10.1681/ASN.2016101150. Swaminathan M., Kopyt N., Atta M.G., Radhakrishnan J., Umanath K., Nguyen S., et al. Pharmacological effects of ex vivo mesenchymal stem cell immunotherapy in patients with acute kidney injury and underlying systemic inflammation. Stem Cell Transl Med. 2021;10:1588–1601. doi: 10.1002/sctm.21-0043. 如果这篇文献综述对您的临床工作有所帮助，欢迎点击文末的“赞”与“推荐(小爱心)”，或转发分享至科室群，让更多同道看到本文；也期待您在留言区留下宝贵见解，与我们交流临床实践中的类似挑战。【获取完整版原文】请点击左下角「阅读原文」下载完整 PDF 文件。

2025-10-02

·GlobeNewswire-Health Care

AM-Pharma Completes Enrollment in Phase 2 Study of Ilofotase Alfa for Prevention of Cardiac Surgery-Associated Renal Damage

Utrecht, The Netherlands, October 2, 2025 – AM-Pharma B.V. today announced that it has successfully completed enrollment of patients in its ongoing Phase 2 clinical trial evaluating ilofotase alfa for the prevention of cardiac surgery-associated renal damage (CSA-RD). CSA-RD, a common cause of Acute Kidney Injury (AKI), is a serious complication of cardiac surgery occurring in up to 40% of patients. AKI following surgery is associated with both short- and long-term impairment of kidney function, an increased risk of requiring renal replacement therapy, sometimes lifelong, and higher mortality rates. Ilofotase alfa is the company’s proprietary therapeutic candidate that has consistently demonstrated safety, tolerability and reno-protective effects, including a reduction in Major Adverse Kidney Events (MAKE), across global clinical trials involving more than 1,000 patients diagnosed with AKI. “CSA-RD represents a serious post-surgical complication, often leading to prolonged hospitalization, increased complications such as the need for renal replacement therapy and a higher long-term risk of chronic kidney disease, end stage renal disease, and mortality,” said Peter Pickkers, MD, PhD, Principal Investigator in the Phase 2 study and Professor of Experimental Intensive Care Medicine at Radboud University Nijmegen Medical Centre, The Netherlands. “With no pharmacological therapies currently available, there is a clear need for novel approaches. This trial is designed to confirm and expand upon the reno-protective effects observed with ilofotase alfa in prior studies, with the goal of developing a meaningful treatment option for patients at risk of kidney injury following cardiac surgery.” The study (NCT06168799) is a multicenter, multinational, randomized, double-blind, placebo-controlled trial that randomized 244 patients at high risk for renal damage following open-heart surgery. Patients received two intravenous (IV) doses, one before and one after surgery, of either 128 mg ilofotase alfa or placebo, and are being followed for 60 days to assess efficacy, safety and pharmacokinetics. The primary endpoint is serum creatinine ratio (sCrR), a sensitive measure of kidney function changes that closely correlates with Major Adverse Kidney Events at 60 days (MAKE60). MAKE60 is an FDA-registrable endpoint, which would serve as the primary endpoint in the expected pivotal Phase 3 trial for ilofotase alfa. Topline data, including data on MAKE60 measured in this study as a secondary endpoint, are expected in early 2026, and the full dataset will be presented thereafter at a scientific conference. “Reaching this enrollment milestone is a key inflection point in the clinical development of ilofotase alfa, bringing us closer to addressing a significant unmet need in hospital care,” said Juliane Bernholz, PhD, Chief Executive Officer of AM-Pharma. “We are grateful to our dedicated clinical partners and the patients for their vital support and trust. With recruitment now complete, we are focused on the data that will inform our next steps to realize the potential for ilofotase alfa to become the first approved therapy to prevent CSA-RD.” About ilofotase alfa Ilofotase alfa is a recombinant alkaline phosphatase, engineered from two human isoforms of the enzyme, which has demonstrated to be highly active and stable in multiple clinical trials. The recombinant enzyme acts by dephosphorylating and detoxifying damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs)—including lipopolysaccharide (LPS), ATP, ADP, and other extracellular substrates—that drive acute inflammation, coagulation, and microvascular ischemia in the kidney following sepsis or ischemia-induced injury. Dephosphorylation of ATP by ilofotase alfa provides dual reno-protective benefits: clearance of pro-inflammatory ATP and generation of adenosine, which activates the tissue-protective adenosine A2a receptor pathway. Through this mechanism, ilofotase alfa has consistently demonstrated safety, tolerability, and reno-protective effects, including a reduction in Major Adverse Kidney Events (MAKE), across clinical studies in patients with sepsis associated-acute kidney injury (SA-AKI), with an even greater effect observed in patients with pre-existing chronic kidney disease (CKD)1. AM-Pharma is developing ilofotase alfa as two distinct therapeutic products: an intravenous (IV) formulation for AKI and a highly concentrated subcutaneous (SC) formulation designed for chronic dosing as enzyme replacement therapy in hypophosphatasia (HPP). A Phase 1b study in adult HPP patients, supported by recent preclinical findings, has reinforced the therapeutic potential of the SC formulation by demonstrating dose-dependent, clinically meaningful effects on key biomarkers (PPi, PLP, and PEA) and showing benefits beyond bone health, including improvements in muscle metabolism and stamina. These effects are particularly relevant for adults with HPP, who often suffer from fatigue and mobility limitations. About cardiac surgery-associated renal damage (CSA-RD) CSA-RD is a clinical complication that arises from acute kidney injury (AKI) following open heart surgery performed with the use of a cardiopulmonary bypass (CPB) pump. Apart from sepsis, this type of surgery is the most frequent cause of AKI. CSA-AKI occurs in about 1 in 3 patients undergoing this surgical procedure.2 There is currently no pharmacological therapy to prevent AKI, and the kidney injury can result in long-term renal impairment as well as the need for renal replacement therapy (RRT) such as dialysis. Notably, mortality can be up to 50% in CSA-AKI patients who require RRT post-operatively. About AM-Pharma AM-Pharma strives to develop medicines for patients confronted with severe medical conditions. Our proprietary asset, ilofotase alfa, is being developed for the treatment of patients with acute kidney injury (AKI) and has been granted FDA fast-track status. We also develop ilofotase alfa in the severe rare disease HPP where ilofotase alfa has orphan drug status in the US and EU. With approximately 1,000 subjects evaluated to date in clinical trials, ilofotase alfa has a proven safety profile and a demonstrated kidney benefit. We are a dedicated team driven to bring treatment options to severely ill patients, their families, and acute care professionals. Find out more about us online at: www.am-pharma.com. Contacts Investors:Juliane Bernholz, Chief Executive Officer j.bernholz@am-pharma.com Media:Trophic CommunicationsEva MulderPhone: +31 6 52 33 15 79am-pharma@trophic.eu 1 Pickkers, P et al., Intensive Care Med., 20242 Andújar A et al., Front. Nephrol., 2023

临床2期快速通道孤儿药临床结果临床1期

2025-10-02

·am-pharma.com

AM-PHARMA COMPLETES ENROLLMENT IN PHASE 2 STUDY OF ILOFOTASE ALFA FOR PREVENTION OF CARDIAC SURGERY-ASSOCIATED RENAL DAMAGE

Utrecht, The Netherlands, October 2, 2025 – AM-Pharma B.V. today announced that it has successfully completed enrollment of patients in its ongoing Phase 2 clinical trial evaluating ilofotase alfa for the prevention of cardiac surgery-associated renal damage (CSA-RD). CSA-RD, a common cause of Acute Kidney Injury (AKI), is a serious complication of cardiac surgery occurring in up to 40% of patients. AKI following surgery is associated with both short- and long-term impairment of kidney function, an increased risk of requiring renal replacement therapy, sometimes lifelong, and higher mortality rates. Ilofotase alfa is the company’s proprietary therapeutic candidate that has consistently demonstrated safety, tolerability and reno-protective effects, including a reduction in Major Adverse Kidney Events (MAKE), across global clinical trials involving more than 1,000 patients diagnosed with AKI. “CSA-RD represents a serious post-surgical complication, often leading to prolonged hospitalization, increased complications such as the need for renal replacement therapy and a higher long-term risk of chronic kidney disease, end stage renal disease, and mortality,” said Peter Pickkers, MD, PhD, Principal Investigator in the Phase 2 study and Professor of Experimental Intensive Care Medicine at Radboud University Nijmegen Medical Centre, The Netherlands. “With no pharmacological therapies currently available, there is a clear need for novel approaches. This trial is designed to confirm and expand upon the reno-protective effects observed with ilofotase alfa in prior studies, with the goal of developing a meaningful treatment option for patients at risk of kidney injury following cardiac surgery.” The study (NCT06168799) is a multicenter, multinational, randomized, double-blind, placebo-controlled trial that randomized 244 patients at high risk for renal damage following open-heart surgery. Patients received two intravenous (IV) doses, one before and one after surgery, of either 128 mg ilofotase alfa or placebo, and are being followed for 60 days to assess efficacy, safety and pharmacokinetics. The primary endpoint is serum creatinine ratio (sCrR), a sensitive measure of kidney function changes that closely correlates with Major Adverse Kidney Events at 60 days (MAKE60). MAKE60 is an FDA-registrable endpoint, which would serve as the primary endpoint in the expected pivotal Phase 3 trial for ilofotase alfa. Topline data, including data on MAKE60 measured in this study as a secondary endpoint, are expected in early 2026, and the full dataset will be presented thereafter at a scientific conference. “Reaching this enrollment milestone is a key inflection point in the clinical development of ilofotase alfa, bringing us closer to addressing a significant unmet need in hospital care,” said Juliane Bernholz, PhD, Chief Executive Officer of AM-Pharma. “We are grateful to our dedicated clinical partners and the patients for their vital support and trust. With recruitment now complete, we are focused on the data that will inform our next steps to realize the potential for ilofotase alfa to become the first approved therapy to prevent CSA-RD.” About ilofotase alfa Ilofotase alfa is a recombinant alkaline phosphatase, engineered from two human isoforms of the enzyme, which has demonstrated to be highly active and stable in multiple clinical trials. The recombinant enzyme acts by dephosphorylating and detoxifying damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs)—including lipopolysaccharide (LPS), ATP, ADP, and other extracellular substrates—that drive acute inflammation, coagulation, and microvascular ischemia in the kidney following sepsis or ischemia-induced injury. Dephosphorylation of ATP by ilofotase alfa provides dual reno-protective benefits: clearance of pro-inflammatory ATP and generation of adenosine, which activates the tissue-protective adenosine A2a receptor pathway. Through this mechanism, ilofotase alfa has consistently demonstrated safety, tolerability, and reno-protective effects, including a reduction in Major Adverse Kidney Events (MAKE), across clinical studies in patients with sepsis associated-acute kidney injury (SA-AKI), with an even greater effect observed in patients with pre-existing chronic kidney disease (CKD)[1]. AM-Pharma is developing ilofotase alfa as two distinct therapeutic products: an intravenous (IV) formulation for AKI and a highly concentrated subcutaneous (SC) formulation designed for chronic dosing as enzyme replacement therapy in hypophosphatasia (HPP). A Phase 1b study in adult HPP patients, supported by recent preclinical findings, has reinforced the therapeutic potential of the SC formulation by demonstrating dose-dependent, clinically meaningful effects on key biomarkers (PPi, PLP, and PEA) and showing benefits beyond bone health, including improvements in muscle metabolism and stamina. These effects are particularly relevant for adults with HPP, who often suffer from fatigue and mobility limitations. About cardiac surgery-associated renal damage (CSA-RD) CSA-RD is a clinical complication that arises from acute kidney injury (AKI) following open heart surgery performed with the use of a cardiopulmonary bypass (CPB) pump. Apart from sepsis, this type of surgery is the most frequent cause of AKI. CSA-AKI occurs in about 1 in 3 patients undergoing this surgical procedure.[2] There is currently no pharmacological therapy to prevent AKI, and the kidney injury can result in long-term renal impairment as well as the need for renal replacement therapy (RRT) such as dialysis. Notably, mortality can be up to 50% in CSA-AKI patients who require RRT post-operatively. About AM-Pharma AM-Pharma strives to develop medicines for patients confronted with severe medical conditions. Our proprietary asset, ilofotase alfa, is being developed for the treatment of patients with acute kidney injury (AKI) and has been granted FDA fast-track status. We also develop ilofotase alfa in the severe rare disease HPP where ilofotase alfa has orphan drug status in the US and EU. With approximately 1,000 subjects evaluated to date in clinical trials, ilofotase alfa has a proven safety profile and a demonstrated kidney benefit. We are a dedicated team driven to bring treatment options to severely ill patients, their families, and acute care professionals. Find out more about us online at: www.am-pharma.com. Contacts Investors: Juliane Bernholz, Chief Executive Officer j.bernholz@am-pharma.com Media: Trophic Communications Eva Mulder Phone: +31 6 52 33 15 79 am-pharma@trophic.eu [1] Pickkers, P et al., Intensive Care Med., 2024 [2] Andújar A et al., Front. Nephrol., 2023

临床2期快速通道孤儿药临床结果临床1期

100 项与 Ilofotase alfa 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
脓毒症所致急性肾损伤	临床3期	美国	AM-Pharma Holding BV	2020-11-02
脓毒症所致急性肾损伤	临床3期	日本	AM-Pharma Holding BV	2020-11-02
脓毒症所致急性肾损伤	临床3期	澳大利亚	AM-Pharma Holding BV	2020-11-02
脓毒症所致急性肾损伤	临床3期	奥地利	AM-Pharma Holding BV	2020-11-02
脓毒症所致急性肾损伤	临床3期	比利时	AM-Pharma Holding BV	2020-11-02
脓毒症所致急性肾损伤	临床3期	加拿大	AM-Pharma Holding BV	2020-11-02
脓毒症所致急性肾损伤	临床3期	丹麦	AM-Pharma Holding BV	2020-11-02
脓毒症所致急性肾损伤	临床3期	芬兰	AM-Pharma Holding BV	2020-11-02
脓毒症所致急性肾损伤	临床3期	法国	AM-Pharma Holding BV	2020-11-02
脓毒症所致急性肾损伤	临床3期	德国	AM-Pharma Holding BV	2020-11-02

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT05890794 (CTgov)	临床1/2期	低碱性磷酸酶血症	12	Ilofotase Alfa, 0.8 mg/kg (0.8 mg/kg Ilofotase Alfa)	衊襯築蓋顧餘窪顧網願(壓壓積憲積遞憲壓鑰醖) = 築選遞顧鬱蓋願獵衊積繭獵鏇衊廠窪積顧夢鏇 (範壓願願襯襯憲構製製, 11.502) 更多	-	2025-02-27
				Ilofotase Alfa, 3.2 mg/kg (3.2 mg/kg Ilofotase Alfa)	衊襯築蓋顧餘窪顧網願(壓壓積憲積遞憲壓鑰醖) = 鏇廠製廠觸憲艱襯網願繭獵鏇衊廠窪積顧夢鏇 (範壓願願襯襯憲構製製, 16.113) 更多
NCT04411472 (REVIVAL \| EudraCT CT Number 2019-0046265-24, CTgov)	临床3期	脓毒症 \| 脓毒性休克 \| 脓毒症所致急性肾损伤	676	Placebo	構積築構鹽餘鹽觸願窪 = 範膚遞鏇壓襯選艱衊糧夢鹹蓋繭廠襯願獵廠窪 (夢顧獵觸觸網構膚餘築, 顧膚淵鹽顧廠膚壓積夢 ~ 構繭築夢獵廠獵鬱艱醖) 更多	-	2024-06-03
NCT04411472 (REVIVAL, Pubmed 1 \| Pubmed 2 \| Intensive Care Med) 人工标引	临床3期	脓毒症所致急性肾损伤	650	Ilofotase alfa	構鏇醖窪鬱獵獵鏇願淵(鹽壓製顧鑰襯糧構窪積) = 鑰遞範醖鹹淵築簾夢網窪遞積網蓋艱顧壓壓鏇 (壓鏇襯鏇鏇顧鹹襯築壓 ) 更多	不佳	2024-01-01
				Placebo	構鏇醖窪鬱獵獵鏇願淵(鹽壓製顧鑰襯糧構窪積) = 觸窪廠壓鏇壓構憲繭範窪遞積網蓋艱顧壓壓鏇 (壓鏇襯鏇鏇顧鹹襯築壓 ) 更多
NCT04411472 (REVIVAL, Corporate Publications) 人工标引	临床3期	脓毒症所致急性肾损伤	649	ilofotase alfa	鬱壓願選膚觸憲觸製襯(願壓壓簾壓觸積餘憲鑰): P-Value = <0.01	不佳	2022-10-20
				Placebo