LNA-043(LNA-043) - 药物靶点：ANGPTL3 x α5β1_在研适应症：膝关节炎_专利_临床

概要

基本信息

药物类型

生物药

别名

靶点

ANGPTL3 x α5β1

作用机制

ANGPTL3抑制剂(血管生成素样蛋白-3抑制剂)、α5β1刺激剂(整合素α-5/β-1复合体刺激剂)

治疗领域

在研适应症

非在研适应症

原研机构

在研机构

Novartis Pharma AGLonza AG

Novartis Pharmaceuticals Corp.

+ [1]

非在研机构-

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)临床2期

特殊审评快速通道 (美国)

登录后查看时间轴

关联

12

项与 LNA-043 相关的临床试验

EUCTR2020-003631-21-EE / Unknown status临床2期

A randomized, four-arm, canakinumab placebo-controlled, participant, investigator and sponsor-blinded study investigating the safety, tolerability and efficacy of intra-articular canakinumab followed by intra-articular LNA043 in patients with knee osteoarthritis

开始日期2022-08-24

申办/合作机构

Novartis Pharma AG

CTR20213160 / Terminated临床2期

一项旨在研究膝关节骨关节炎患者在卡那奴单抗关节内给药后接受LNA043关节内给药的安全性、耐受性和疗效的受试者、研究者和申办方设盲的随机、4组、安慰剂对照研究

这是一项IIa期概念验证研究，包括4个治疗组（TA1-4），旨在确定LNA043在根据MRI确定的伴有炎症的症状性膝关节OA患者中的疗效。研究的目的包括评估能否确定i.a. LNA043在炎症性膝关节OA患者中的疗效评估能否通过合用抗炎药物（i.a.卡那奴单抗）克服炎症的潜在不利影响评估i.a.卡那奴单抗在缓解疼痛及其他临床症状和改善功能方面的疗效

开始日期2022-07-19

申办/合作机构

诺华中国

[+2]

CTR20212035 / Active, not recruiting临床2期

评价LNA043治疗膝骨关节炎的有效性、安全性和耐受性的为期5年、随机、双盲、安慰剂对照、多中心的IIb期研究

评价LNA043不同剂量（20 mg和40 mg）、一个给药周期的不同注射次数（1 vs 3）和不同给药周期频率（每6个月 vs 每 12 个月）关节内给药治疗膝骨关节炎的有效性、安全性和耐受性。

开始日期2021-11-10

申办/合作机构

诺华中国

[+2]

100 项与 LNA-043 相关的临床结果

登录后查看更多信息

100 项与 LNA-043 相关的转化医学

登录后查看更多信息

100 项与 LNA-043 相关的专利（医药）

登录后查看更多信息

2

项与 LNA-043 相关的文献（医药）

2023-09-01·Osteoarthritis and Cartilage

Towards disease modification in osteoarthritis

Communications

作者: Dell'Accio, Francesco ; De Bari, Cosimo

In December 2022, Gerwin et al published in Nature Medicine that the C-terminal portion of angiopoietin-like 3, called LNA043, has chondroprotective and cartilage-regenerative properties. Molecular data from an experimental medicine phase I study suggested potential efficacy in humans. Here, we respond to and complement a commentary from Vincent and Conaghan and discuss unresolved issues and the potential of this molecule as a disease-modifying osteoarthritis drug.

2022-12-01·Nature Medicine1区 · 医学

Angiopoietin-like 3-derivative LNA043 for cartilage regeneration in osteoarthritis: a randomized phase 1 trial

1区 · 医学

Article

作者: Glowacki, Gustavo ; Polus, Florine ; Li, Yufei ; Seroutou, Abdelkader ; Brachat, Sophie ; Walter, Sandra ; Shi, Jian ; Peters, Thomas ; Kneissel, Michaela ; Choudhury, Subhajit ; Goldhahn, Jörg ; Roubenoff, Ronenn ; Scotti, Celeste ; Schieker, Matthias ; Belaud, Magali ; Vostiar, Igor ; Paul, Jochen ; Laurent, Didier ; Laplanche, Nelly ; Gimbel, Joseph ; Kramer, Ina ; Fornaro, Mara ; Zhang, Yunyu ; Gerwin, Nicole ; Halleux, Christine ; Elliott, Jimmy ; Wharton, Keith A ; Johnson, Kristen ; Guth, Sabine ; Jacobi, Carsten

AbstractOsteoarthritis (OA) is a common, debilitating, chronic disease with no disease-modifying drug approved to date. We discovered LNA043—a derivative of angiopoietin-like 3 (ANGPTL3)—as a potent chondrogenesis inducer using a phenotypic screen with human mesenchymal stem cells. We show that LNA043 promotes chondrogenesis and cartilage matrix synthesis in vitro and regenerates hyaline articular cartilage in preclinical OA and cartilage injury models in vivo. LNA043 exerts at least part of these effects through binding to the fibronectin receptor, integrin α5β1on mesenchymal stem cells and chondrocytes. In a first-in-human (phase 1), randomized, double-blinded, placebo-controlled, single ascending dose, single-center trial (NCT02491281; sponsored by Novartis Pharmaceuticals), 28 patients with knee OA were injected intra-articularly with LNA043 or placebo (3:1 ratio) either 2 h, 7 d or 21 d before total knee replacement. LNA043 met its primary safety endpoint and showed short serum pharmacokinetics, cartilage penetration and a lack of immunogenicity (secondary endpoints). Post-hoc transcriptomics profiling of cartilage revealed that a single LNA043 injection reverses the OA transcriptome signature over at least 21 d, inducing the expression of hyaline cartilage matrix components and anabolic signaling pathways, while suppressing mediators of OA progression. LNA043 is a novel disease-modifying OA drug candidate that is currently in a phase 2b trial (NCT04864392) in patients with knee OA.

100 项与 LNA-043 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

登录

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
膝关节炎	临床2期	美国	Novartis Pharmaceuticals Corp.	2017-09-12
膝关节炎	临床2期	捷克	Novartis Pharmaceuticals Corp.	2017-09-12
膝关节炎	临床2期	丹麦	Novartis Pharmaceuticals Corp.	2017-09-12
软骨病变	临床前	丹麦	Novartis Pharmaceuticals Corp.	2017-09-12
软骨病变	临床前	捷克	Novartis Pharmaceuticals Corp.	2017-09-12
软骨病变	临床前	美国	Novartis Pharmaceuticals Corp.	2017-09-12
软骨病变	临床前	丹麦	Novartis Pharmaceuticals Corp.	2017-09-12
软骨病变	临床前	美国	Novartis Pharmaceuticals Corp.	2017-09-12
软骨病变	临床前	捷克	Novartis Pharmaceuticals Corp.	2017-09-12
膝关节原发性骨关节炎 NOS	临床前	美国	Novartis Pharmaceuticals Corp.	2015-11-16