A Randomized, Open-Label, Parallel Group, Phase 1 Study to Assess the Pharmacodynamic Effect of AP301 on Urinary Phosphorus Excretion in Healthy Volunteers

This is a randomized, open-label, parallel-group, phase 1 study to evaluate the PD effect of AP301 capsule in healthy volunteers. The study is planned to have 4 treatment arms: Arm 1: 2.10 g/day; arm 2: 4.20 g/day; arm 3: 6.30 g/day; arm 4: 8.40 g/day.

Start Date11 Jan 2024

Sponsor / Collaborator

Shanghai Alebund Pharmaceuticals Co., Ltd.

CTR20231624 / Active, not recruitingPhase 3

一项在慢性肾脏病接受维持性透析的高磷血症患者中评价 AP301控制血清磷的有效性和安全性的随机、开放性、多中心 III 期研究

[Translation] A randomized, open-label, multicenter phase III study to evaluate the efficacy and safety of AP301 in controlling serum phosphorus in patients with hyperphosphatemia and chronic kidney disease receiving maintenance dialysis

主要目的 1. 评估 AP301 维持剂量组对透析高磷血症患者血清磷的控制是否优于AP301 低剂量对照组。 2. 评估 AP301 组对透析高磷血症患者血清磷的控制是否非劣于碳酸司维拉姆组。次要目的有效性： 1. 评估 AP301 对透析高磷血症患者血清磷控制的综合疗效。 2. 评估 AP301 对透析高磷血症患者血清钙、钙磷乘积（Ca×P）和全段甲状旁腺激素（iPTH）水平变化的影响。安全性： 1. 评估 AP301 在透析高磷血症患者中的安全性和耐受性。

[Translation]

Primary Objectives 1. To evaluate whether the AP301 maintenance dose group is better than the AP301 low-dose control group in controlling serum phosphorus in patients with dialysis hyperphosphatemia. 2. To evaluate whether the AP301 group is non-inferior to the sevelamer carbonate group in controlling serum phosphorus in patients with dialysis hyperphosphatemia. Secondary Objectives Efficacy: 1. To evaluate the comprehensive efficacy of AP301 in controlling serum phosphorus in patients with dialysis hyperphosphatemia. 2. To evaluate the effect of AP301 on changes in serum calcium, calcium-phosphorus product (Ca×P) and intact parathyroid hormone (iPTH) levels in patients with dialysis hyperphosphatemia. Safety: 1. To evaluate the safety and tolerability of AP301 in patients with dialysis hyperphosphatemia.

Start Date12 Jun 2023

Sponsor / Collaborator

Shanghai Alebund Pharmaceuticals Co., Ltd.

[+1]

CTR20200180 / CompletedPhase 2

一项评估VS-505剂量递增及不同固定剂量与碳酸司维拉姆相比在慢性肾脏病接受维持透析治疗的高磷血症患者中降低血清磷的耐受性、安全性及有效性研究

[Translation] A study to evaluate the tolerability, safety, and efficacy of VS-505 at dose escalation and different fixed doses compared with sevelamer carbonate in lowering serum phosphorus in patients with hyperphosphatemia receiving maintenance dialysis for chronic kidney disease

本研究分为无缝衔接的两部分，研究主体是第二部分：VS-505的五个不同固定剂量组与碳酸司维拉姆相比，在CKD接受维持透析治疗的高磷血症患者中降低血清磷的安全性及有效性研究。根据国家药品监督管理局意见，本研究增加了第一部分25例患者的剂量爬坡试验，旨在于中国CKD接受维持透析治疗的高磷血症患者群体中评估VS-505的耐受性

[Translation]

This study is divided into two parts that are seamlessly connected. The main part of the study is the second part: a safety and efficacy study of five different fixed dose groups of VS-505 compared with sevelamer carbonate in reducing serum phosphorus in patients with hyperphosphatemia receiving maintenance dialysis for CKD. According to the opinion of the National Medical Products Administration, this study added a dose escalation trial of 25 patients in the first part to evaluate the tolerability of VS-505 in the Chinese CKD patient population with hyperphosphatemia receiving maintenance dialysis.

Start Date13 Oct 2020

Sponsor / Collaborator

Orient Pharma Co., Ltd.

[+2]

100 Clinical Results associated with VS-505

100 Translational Medicine associated with VS-505

100 Patents (Medical) associated with VS-505

Literatures (Medical) associated with VS-505

27 Sep 2024·Nephrology Dialysis Transplantation

Tolerability, safety and efficacy of a novel phosphate binder VS-505 (AP301): a Phase 2 dose-escalation and dose-ranging study in patients undergoing maintenance hemodialysis

Article

Author: Luo, Yuan ; Lin, Hongli ; Liu, Yingxue Cathy ; Zhuang, Bing ; Shi, Ming ; Zhang, Weifeng ; Lu, Wei ; Zhang, Shiying ; Wang, Lihua ; Zuo, Li ; He, Qiang ; Luo, Ping ; Liu, Changhua ; Wang, Song ; Liu, Tongqiang ; Liu, Bin ; Zheng, Huixiao ; Li, Kanghui ; Chen, Xiaolan ; Yuan, Weijie ; Zhang, Zhizheng ; Yang, Junwei ; Long, Gang ; Li, Xiaoling ; Peng, Ai ; Zheng, Feng ; Wang, Baoxing ; Gan, Liangying ; Li, Yiwen ; Ye, Hong ; Gao, Qing

ABSTRACTBackgroundVS-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).MethodsIn 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.ResultsThe 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.ConclusionVS-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.Clinical Trial registration numberNCT04551300

01 Jan 2023·Frontiers in immunology

Direct endothelial ENaC activation mitigates vasculopathy induced by SARS-CoV2 spike protein.

Article

Author: Fulton, David ; Hamacher, Jürg ; Fischer, Bernhard ; Mraheil, Mobarak A ; Sridhar, Supriya ; Zeitlinger, Markus ; Eaton, Douglas C ; Singla, Bhupesh ; Annex, Brian H ; Romero, Maritza J ; Csanyi, Gabor ; Moseley, Auriel S ; Song, Chang ; Chakraborty, Trinad ; Yue, Qian ; Gan, Lin ; Lucas, Rudolf

IntroductionAlthough both COVID-19 and non-COVID-19 ARDS can be accompanied by significantly increased levels of circulating cytokines, the former significantly differs from the latter by its higher vasculopathy, characterized by increased oxidative stress and coagulopathy in lung capillaries. This points towards the existence of SARS-CoV2-specific factors and mechanisms that can sensitize the endothelium towards becoming dysfunctional. Although the virus is rarely detected within endothelial cells or in the circulation, the S1 subunit of its spike protein, which contains the receptor binding domain (RBD) for human ACE2 (hACE2), can be detected in plasma from COVID-19 patients and its levels correlate with disease severity. It remains obscure how the SARS-CoV2 RBD exerts its deleterious actions in lung endothelium and whether there are mechanisms to mitigate this.MethodsIn this study, we use a combination of in vitro studies in RBD-treated human lung microvascular endothelial cells (HL-MVEC), including electrophysiology, barrier function, oxidative stress and human ACE2 (hACE2) surface protein expression measurements with in vivo studies in transgenic mice globally expressing human ACE2 and injected with RBD.ResultsWe show that SARS-CoV2 RBD impairs endothelial ENaC activity, reduces surface hACE2 expression and increases reactive oxygen species (ROS) and tissue factor (TF) generation in monolayers of HL-MVEC, as such promoting barrier dysfunction and coagulopathy. The TNF-derived TIP peptide (a.k.a. solnatide, AP301) -which directly activates ENaC upon binding to its a subunit- can override RBD-induced impairment of ENaC function and hACE2 expression, mitigates ROS and TF generation and restores barrier function in HL-MVEC monolayers. In correlation with the increased mortality observed in COVID-19 patients co-infected with S. pneumoniae, compared to subjects solely infected with SARS-CoV2, we observe that prior intraperitoneal RBD treatment in transgenic mice globally expressing hACE2 significantly increases fibrin deposition and capillary leak upon intratracheal instillation of S. pneumoniae and that this is mitigated by TIP peptide treatment.

01 Jan 2022·Computational and Structural Biotechnology Journal

Conformational ensemble of the TNF-derived peptide solnatide in solution

Article

Author: Eaton, Douglas C ; Fischer, Bernhard ; Arrastia-Casado, Silvia ; Fischer, Hendrik ; Martin-Malpartida, Pau ; Lucas, Rudolf ; Tzotzos, Susan ; Farrera-Sinfreu, Josep ; Macias, Maria J

Tumor necrosis factor (TNF) is a homotrimer that has two spatially distinct binding regions, three lectin-like domains (LLD) at the TIP of the protein and three basolaterally located receptor-binding sites, the latter of which are responsible for the inflammatory and cell death-inducing properties of the cytokine. Solnatide (a.k.a. TIP peptide, AP301) is a 17-mer cyclic peptide that mimics the LLD of human TNF which activates the amiloride-sensitive epithelial sodium channel (ENaC) and, as such, recapitulates the capacity of TNF to enhance alveolar fluid clearance, as demonstrated in numerous preclinical studies. TNF and solnatide interact with glycoproteins and these interactions are necessary for their trypanolytic and ENaC-activating activities. In view of the crucial role of ENaC in lung liquid clearance, solnatide is currently being evaluated as a novel therapeutic agent to treat pulmonary edema in patients with moderate-to-severe acute respiratory distress syndrome (ARDS), as well as severe COVID-19 patients with ARDS. To facilitate the description of the functional properties of solnatide in detail, as well as to further target-docking studies, we have analyzed its folding properties by NMR. In solution, solnatide populates a set of conformations characterized by a small hydrophobic core and two electrostatically charged poles. Using the structural information determined here and also that available for the ENaC protein, we propose a model to describe solnatide interaction with the C-terminal domain of the ENaCα subunit. This model may serve to guide future experiments to validate specific interactions with ENaCα and the design of new solnatide analogs with unexplored functionalities.

100 Deals associated with VS-505

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Chronic Kidney Diseases	Phase 3	CN	Libang Biomedical (Jiangsu) Co., Ltd.	12 Jun 2023
Hyperphosphatemia	Phase 3	CN	Libang Biomedical (Jiangsu) Co., Ltd.	12 Jun 2023

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04551300 (Pubmed) Manual	Phase 2	Hyperphosphatemia Maintenance	130	VS-505 2.25- 9.00 g/day (dose-escalated treatment)	(mrigarzrgu) = kweamfmupe fwidpeivlh (lrnsjfhzsh, -2.7 to -1.4)	Positive	07 Mar 2024
				VS-505 1.50 g/day (andomized, open-label, fixed-dosage treatment)	(mrigarzrgu) = tsjxjrzvfh fwidpeivlh (lrnsjfhzsh )
ERS2015	Not Applicable	Primary Graft Dysfunction	20	AP301	intitgwdai(fbclmjqkat) = smlkdylovn rbngcrtnaj (zqeozgpetm )	Positive	01 Sep 2015
1R43DK096698-01 (ASN2014)	Not Applicable	-	-	VS-505	lbthecsqsf(olildogvsg) = More aortic calcification was observed in 5/6 NX rats treated with 5% sevelamer, while VS-505 and sevelamer did not show significant effects on cardiac parameters, fibrosis, intestine histology and intestinal sodium-dependent phosphate cotransporter gene expression pdannsihbm (twdtvfqaon ) View more	Positive	11 Nov 2014
				Sevelamer

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

VS-505

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation