Delving into the Latest Updates on Aletekitug with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

Target

IL-18

Mechanism

IL-18 inhibitors(Interleukin 18 inhibitors)

Therapeutic Areas

Immune System DiseasesCongenital DisordersSkin and Musculoskeletal Diseases

Active Indication

Moderate Atopic DermatitisSevere Atopic DermatitisDermatitis, Atopic

Inactive Indication

Crohn DiseaseDelayed Graft FunctionDiabetes Mellitus, Type 2+ [2]

Originator Organization

GSK Plc

Active Organization

GSK PlcGlaxosmithkline Intellectual Property Development Ltd.GlaxoSmithKline Research & Development Ltd.

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Gene Sequence

Sequence Code 42938H

Source: *****

Sequence Code 42942L

Source: *****

主要目的：评价GSK1070806 200 MG与安慰剂相比在中度至重度ATD成人中的疗效。次要目的：通过表征中度至重度ATD成人的纵向剂量-反应关系，评价剂量范围内GSK1070806与安慰剂相比的疗效; 进一步评价GSK1070806 200 MG和整个剂量范围与安慰剂相比在中度至重度ATD成人中的影响; 进一步评价GSK1070806 200 MG和整个剂量范围与安慰剂相比在中度至重度ATD成人中的疗效; 在中度至重度ATD成人中评估GSK1070806 200 MG和整个剂量范围与安慰剂相比对通过一系列患者报告结局PRO测量的健康相关生活质量(HR-QOL)、抑郁和焦虑、疲劳、睡眠、WPAI和疼痛的影响; 评估GSK1070806 200 MG在中度至重度ATD成人中的安全性和剂量范围内的安全性。

[Translation]

Primary objective: To evaluate the efficacy of GSK1070806 200 MG compared with placebo in adults with moderate to severe ATD. Secondary objectives: To evaluate the efficacy of GSK1070806 compared to placebo across a dose range by characterizing the longitudinal dose-response relationship in adults with moderate to severe ATD; To further evaluate the effects of GSK1070806 200 MG and the entire dose range compared to placebo in adults with moderate to severe ATD; To further evaluate the efficacy of GSK1070806 200 MG and the entire dose range compared to placebo in adults with moderate to severe ATD; To evaluate the effects of GSK1070806 200 MG and the entire dose range compared to placebo on health-related quality of life (HR-QOL), depression and anxiety, fatigue, sleep, WPAI, and pain measured by a battery of patient-reported outcomes PROs in adults with moderate to severe ATD; To evaluate the safety of GSK1070806 200 MG and the entire dose range in adults with moderate to severe ATD and across a dose range.

Start Date28 Mar 2024

Sponsor / Collaborator

GlaxoSmithKline LLC

[+2]

JPRN-jRCT2071230084 / RecruitingPhase 2IIT

A Phase 2b, Randomized, Double-Blind, Parallel Group, Placebo Controlled, Dose Finding study to evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of GSK1070806 SC injection in Adult Participants with Moderate to Severe Atopic Dermatitis

Start Date12 Dec 2023

Sponsor / Collaborator-

100 Clinical Results associated with Aletekitug

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100 Translational Medicine associated with Aletekitug

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100 Patents (Medical) associated with Aletekitug

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5

Literatures (Medical) associated with Aletekitug

01 Sep 2017·Clinical ScienceQ2 · MEDICINE

Cytokines of the IL-1 family: recognized targets in chronic inflammation underrated in organ transplantations

Q2 · MEDICINE

Review

Author: Striz, Ilja

Interleukin 1 (IL-1) family is a group of cytokines with multiple local and systemic effects, which regulates both innate and adaptive immune responses. Generally, most IL-1 family cytokines express prevailing pro-inflammatory activities (IL-1α, IL-1β, IL-18, IL-33, IL-36 α, β, γ), whereas others are anti-inflammatory (IL-1Ra (IL-1 receptor antagonist), IL-36Ra, IL-38, IL-37). In addition to their immunomodulatory roles, some of them are also involved in the physiological modulation of homeostatic processes and directly affect mRNA transcription. IL-1 family cytokines bind to specific receptors composed of a ligand-binding chain and an accessory chain. The pro-inflammatory effects of IL-1 family cytokines are regulated on the level of transcription, enzymatic processing of precursors, release of soluble antagonists, and expression of decoy receptors. Members of the IL-1 family regulate the recruitment and activation of effector cells involved in innate and adaptive immunity, but they are also involved in the pathogenesis of chronic disorders, including inflammatory bowel disease, rheumatoid arthritis, and various autoimmune and autoinflammatory diseases. There are only limited data regarding the role of IL-1 cytokines in transplantation. In recent years, targeted therapeutics affecting IL-1 have been used in multiple clinical studies. In addition to the recombinant IL-1Ra, anakinra (highly effective in autoinflammatory diseases and tested for other chronic diseases), the monoclonal antibodies canakinumab, gevokizumab, and rilonacept (a long-acting IL-1 receptor fusion protein) provide further options to block IL-1 activity. Furthermore, new inhibitors of IL-18 (GSK 1070806, ABT-325, rIL-18BP (IL-18 binding protein)) and IL-33 (CNTO-7160) are presently under clinical studies and other molecules are being developed to target IL-1 family cytokines.

01 Oct 2014·Int. Journal of Clinical Pharmacology and TherapeuticsQ4 · MEDICINE

Safety, tolerability, pharmacokinetics, and pharmacodynamics of single-dose antiinterleukin- 18 mAb GSK1070806 in healthy and obese subjects

Q4 · MEDICINE

Article

Author: Reid, Juliet ; Mistry, Prafull ; Abberley, Lee ; DeWal, Stephen ; Pouliquen, Isabelle ; Taylor, Adam ; del Cura, Marian Rocha ; McHugh, Simon ; Tong, Xin ; McKie, Elizabeth

OBJECTIVETo investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of GSK1070806, a novel IgG1 mAb that neutralizes human interleukin (IL)-18.METHODSIn this first-timein-human (FTIH) study, cohorts of healthy and obese subjects were randomly allocated to receive single doses of GSK1070806 (0.008 - 10 mg/kg) or placebo. Blood was sampled ≤ 274 days post-dosing, and safety monitored.RESULTSGSK1070806 was generally well tolerated. The most common AEs were nasopharyngitis and headache, arising as frequently in the placebo as in the active drug groups; most AEs were mild to moderate and unrelated to dose level. There were no allergic, delayed-type hypersensitivity, or infusion-related reactions and the incidence of immunogenicity was low. GSK1070806 plasma pharmacokinetic profiles were comparable in healthy and obese subjects; there was no major deviation from dose proportionality for AUC(∞) and C(max) although a trend for dose-dependent increase in t(1/2) was observed. Serum drug-bound IL-18 levels increased post-dosing and were sustained for a long time-period following GSK1070806 administration. Ex-vivo whole blood assay demonstrated prolonged pharmacological activity of GSK1070806 as determined by its primary immunological mechanism of action, inhibition of IL-18-induced IFN-γ production.CONCLUSIONGSK1070806 warrants clinical investigation in patients.

PLOS ONEQ3 · CROSS-FIELD

A Study to Investigate the Efficacy and Safety of an Anti-Interleukin-18 Monoclonal Antibody in the Treatment of Type 2 Diabetes Mellitus

Q3 · CROSS-FIELD

ArticleOA

Author: DeWall, Stephen L ; Ambery, Philip D ; Gil-Extremera, Blas ; Reid, Juliet L ; Mistry, Prafull C ; McKie, Elizabeth A ; Abberley, Lee

OBJECTIVEEvidence suggests that chronic subclinical inflammation plays an important role in the pathogenesis of type 2 diabetes (T2DM). Circulating levels of interleukin (IL)-18 appear to be associated with a number of micro- and macrovascular comorbidities of obesity and T2DM. This study was designed to investigate whether inhibition of IL-18 had any therapeutic benefit in the treatment of T2DM. Preliminary efficacy, safety and tolerability, pharmacokinetics, and pharmacodynamics of the anti-IL-18 monoclonal antibody, GSK1070806, were assessed.RESEARCH DESIGN AND METHODSThis was a multicentre, randomized, single-blind (sponsor-unblinded), placebo-controlled, parallel-group, phase IIa trial. Obese patients of either sex, aged 18-70 years, with poorly controlled T2DM on metformin monotherapy were recruited. Patients received two doses, of placebo (n = 12), GSK1070806 0.25 mg/kg (n = 13) or GSK1070806 5 mg/kg (n = 12). The primary end-point was the change from baseline in fasting plasma glucose and weighted mean glucose area under the curve (AUC)(0-4 hours) postmixed meal test on Days 29, 57, and 85.RESULTSThirty-seven patients were randomized to one of the three treatment arms. There were no statistically significant effects of GSK1070806 doses on fasting plasma glucose levels, or weighted mean glucose AUC(0-4 hours) compared with placebo.CONCLUSIONSGSK1070806 was well tolerated, and inhibition of IL-18 did not lead to any improvements in glucose control. However, because of study limitations, smaller, potentially clinically meaningful effects of IL-18 inhibition cannot be excluded.TRIAL REGISTRATIONClinicalTrials.gov NCT01648153.

100 Deals associated with Aletekitug

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Severe Atopic Dermatitis	Phase 2	ES	GSK Plc	16 Nov 2023
Crohn Disease	Phase 1	GB	GSK Plc	20 Feb 2019
Delayed Graft Function	Phase 1	ES	GSK Plc	27 Aug 2016
Delayed Graft Function	Phase 1	GB	GSK Plc	27 Aug 2016
Renal transplant rejection	Phase 1	GB	GSK Plc	27 Aug 2016
Renal transplant rejection	Phase 1	ES	GSK Plc	27 Aug 2016
Diabetes Mellitus, Type 2	Phase 1	GB	GSK Plc	01 Aug 2012
Diabetes Mellitus, Type 2	Phase 1	ES	GSK Plc	01 Aug 2012
Obesity	Phase 1	ES	GSK Plc	01 Aug 2012
Obesity	Phase 1	GB	GSK Plc	01 Aug 2012

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04975438 (CTgov)	Phase 1	Moderate Atopic Dermatitis \| Severe Atopic Dermatitis	34	GSK1070806 (Group 1: GSK1070806)	usvefsjvee(dxncbqjwug) = dwdnbttswe ejkbovxfsb (crybesfodg, dlgimnfjqk - ahzzjgxbtz) View more	-	23 Jul 2024
NCT04975438 (CTgov)	Phase 1	Moderate Atopic Dermatitis \| Severe Atopic Dermatitis	34	Placebo (Group 1: Placebo)	usvefsjvee(dxncbqjwug) = nkcgdbllrw ejkbovxfsb (crybesfodg, laqaiuhhoq - okacwrsnjf) View more	-	23 Jul 2024
GSK1070806 (EADV2023)	Phase 1	-	-	GSK1070806	dqchsnckva(zolankaedy) = eprzyrfzen ogmfqpsnkv (okcjhqsafx )	Positive	11 Oct 2023
NCT02723786 (Pubmed \| J Biol Chem) Manual	Phase 2	Delayed Graft Function	7	GSK1070806	fzbenbnzcb(sdyaesmzug) = wmjqtwwukk jzmcknjmqj (lzrwpsgndc ) View more	Negative	08 Mar 2021
NCT02723786 (CTgov)	Phase 2	Renal transplant rejection \| Delayed Graft Function	7	GSK1070806+basiliximab+tacrolimus+azathioprine+mycophenolate mofetil	musybigbwn(ntsjowznug) = hflyjgpwor ukbwcanlve (fbtdrijvsk, bgqdxhojuj - hrdbntskje) View more	-	10 Jun 2019