HL-2351(HL-2351) - 药物靶点：IL1R1_在研适应症：Cryopyrin相关周期性综合征，类风湿关节炎_专利_临床

概要

基本信息

药物类型

融合蛋白

别名

rhIL-1Ra-hyFc

+ [2]

靶点

IL1R1

作用机制

IL1R1拮抗剂(白细胞介素-1受体拮抗剂)

治疗领域

遗传病与畸形皮肤和肌肉骨骼疾病其他疾病+ [1]

在研适应症

Cryopyrin相关周期性综合征类风湿关节炎

非在研适应症-

原研机构

Genexine, Inc.

在研机构

Genexine, Inc.

非在研机构

Handok, Inc.

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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关联

3

项与 HL-2351 相关的临床试验

NCT02853084 / Terminated临床2期

An Open Label, Single Arm Trial to Evaluate the Efficacy, Safety, and Pharmacokinetics of HL2351 in Patients With Cryopyrin Associated Periodic Syndromes

This is an open label, single arm trial to evaluate the efficacy, safety, and pharmacokinetics of HL2351 in patients with cryopyrin associated periodic syndromes (CAPS).

开始日期2015-10-01

申办/合作机构

Handok, Inc.

KCT0001184 / Completed临床1期IIT

A Dose-Block Randomized, Placebo controlled (Double-blind), Active Controlled(Open-label), Dose-escalation Study to investigate the tolerability, and Pharmacokinetics/Pharmacodynamics of HL2351 after a Single Subcutaneous Administration in Healthy Male Subjects

开始日期2014-06-09

申办/合作机构

Seoul National University Hospital

NCT02175056 / Completed临床1期

A Dose-Block Randomized, Placebo Controlled (Double-blind), Active Controlled(Open-label), Dose-escalation Study to Investigate the Tolerability, and Pharmacokinetics/Pharmacodynamics of HL2351 After a Single Subcutaneous Administration in Healthy Male Subjects

The study design of this trial is a Dose-Block Randomized, Placebo controlled (Double-blind), Active Controlled(Open-label), Dose-escalation.

开始日期2014-05-01

申办/合作机构

Handok, Inc.

100 项与 HL-2351 相关的临床结果

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100 项与 HL-2351 相关的转化医学

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100 项与 HL-2351 相关的专利（医药）

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3

项与 HL-2351 相关的文献（医药）

2020-10-01·CPT: Pharmacometrics & Systems Pharmacology3区 · 医学

Development of a Pharmacokinetic Model Describing Neonatal Fc Receptor‐Mediated Recycling of HL2351, a Novel Hybrid Fc‐Fused Interleukin‐1 Receptor Antagonist, to Optimize Dosage Regimen

3区 · 医学

ArticleOA

作者: Kim, Anhye ; Back, Hyun‐moon ; Oh, Jaeseong ; Kang, Won‐ho ; Yun, Hwi‐yeol ; Chae, Jung‐woo ; Lee, Howard ; Ngo, Lien

HL2351 (hIL‐1Ra‐hyFc) is a novel recombinant protein formed by the fusion of two human interleukin‐1 receptor antagonist components into one antibody‐derived fragment crystallizable portion. Although HL2351 has a pharmacological mechanism of action similar to that of anakinra as a commercialized biopharmaceutical drug, HL2351 has been desired to reduce the dose frequency and improve therapeutic efficacy due to its long circulation half‐life. In this study, we aimed to develop a population pharmacokinetic (PK) model for HL2351 using a neonatal Fc receptor (FcRn)–mediated recycling model based on a quasi‐steady‐state approximation of target‐mediated drug disposition (TMDD) for the description of interactions between the drug and FcRn. FcRn recycling was expected in the case of HL2351 because of PK related to the antibody portion. A TMDD model was also applied to describe interactions of IL1R with HL2351 or anakinra. PK data were collected from a phase I study conducted in six groups (1, 2, 4, 8, 12 mg/kg HL2351 and 100 mg anakinra single subcutaneous administration; n = 8 per group). In consequence, the PK of anakinra and HL2351 following administration of multiple doses at different dosages were simulated. Optimized doses were considered based on average concentrations of IL1R bound to anakinra and HL2351. HL2351 at doses of 326 mg or 4.267, 4.982, 5.288, 5.458, or 5.748 mg/kg once weekly or HL2351 at 1726 mg or 21.92, 26.86, 29.10, 30.36, or 32.53 mg/kg once biweekly would have similar therapeutic effects with anakinra at a dose of 100 mg or 1, 2, 3, 4, or 8 mg/kg administered once daily, respectively.

2020-02-01·British Journal of Clinical Pharmacology2区 · 医学

Safety, tolerability and pharmacokinetics and pharmacodynamics of HL2351, a novel hybrid fc‐fused interleukin‐1 receptor antagonist, in healthy subjects: A first‐in‐human study

2区 · 医学

Article

作者: Huh, Ki Young ; Park, Sung Sup ; Lee, Howard ; Yoon, Seo Hyun ; Kim, Se‐Jin ; Yoon, Hyunyee ; Cha, Ji‐Eun ; Cho, Young‐Gyu ; Lee, Jieon ; Oh, Jaeseong

AimsWe performed a first‐in‐human study with HL2351, a novel hybrid Fc‐fused interleukin (IL)‐1 receptor antagonist, to evaluate its tolerability, pharmacokinetics and pharmacodynamics (PD) after a single subcutaneous (SC) administration in healthy subjects.MethodsA randomized, double‐blind, placebo‐ and active‐controlled, dose‐escalation study was conducted. Eligible subjects randomly received a single SC administration of HL2351 (1, 2, 4, 8 and 12 mg/kg) or placebo in a ratio of 8:2. Subjects in the active‐controlled group received a single SC administration of anakinra at 100 mg. Serial blood samples were collected for pharmacokinetics and PD analyses. An ex‐vivo activation test was performed to evaluate the PD using peripheral blood mononuclear cells treated with IL‐1β. Anti‐HL2351 antibodies were determined at baseline and 29 days postdose. Tolerability was assessed throughout the study.ResultsHL2351 was eliminated more slowly than anakinra (terminal half‐life: 27.21–45.28 vs 3.97 h). Serum concentrations of HL2351 were increased dose‐proportionally. The mean apparent clearance of HL2351 were 0.6, 0.66, 0.75, 0.51, 0.65 L/h at 1, 2, 4, 8 and 12 mg/kg, respectively. The percent inhibition of IL‐6 expression varied widely (range: 0–92.1%), showing no clear trend or discernible difference between HL2351, anakinra and placebo. HL2351 was well tolerated after a single SC administration.ConclusionHL2351 was well tolerated and showed linear pharmacokinetic characteristics after a single SC administration at doses up to 12 mg/kg in healthy subjects. HL2351 remained in the body 7‐11 times longer than anakinra. HL2351 can be developed as a potential therapeutic alternative to anakinra.

2007-08-01·Biomaterials

The effect of covalently immobilized rhIL-1ra-ELP fusion protein on the inflammatory profile of LPS-stimulated human monocytes

Article

作者: Jason T. Smith ; William M. Reichert ; Dong-Hwan Kim ; Ashutosh Chilkoti

The objective of this research was to investigate whether immobilized anti-inflammatory cytokines will signal changes in the inflammatory profile of cultured monocytes. A fusion protein of recombinant human IL-1 receptor antagonist and elastin-like peptide (IL-1ra-ELP) was expressed in Escherichia coli. THP-1 human monocytes were cultured on either carboxyl-terminated self-assembled monolayers (SAMs), or SAMs with either covalently immobilized or soluble IL-1ra-ELP. LPS-stimulated monocytes exposed to either soluble or immobilized IL-1ra-ELP were prevented from cell differentiation, showed attenuated expression of pro-inflammatory cytokines, and had increased production of anti-inflammatory and pro-wound healing cytokines. These results suggest that immobilized anti-inflammatory cytokines have the potential to be immunomodulatory biomaterials.

100 项与 HL-2351 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
Cryopyrin相关周期性综合征	临床2期	-	Genexine, Inc.	-
类风湿关节炎	临床2期	韩国	Handok, Inc.	-
类风湿关节炎	临床1期	-	Genexine, Inc.	-