A 12-week, multi-center, double-blinded, parallel-group, randomized, placebo-controlled phase IIb study to evaluate the safety, tolerability and efficacy of IZD334 to reduce CRP in cardiovascular high-risk patients

Start Date16 Jul 2020

Sponsor / Collaborator-

NCT04086602 / CompletedPhase 1

A Phase 1, Randomised, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Determine the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of IZD334 in Healthy Adult Participants as Well as an Open-label Cohort to Confirm the Safety, Pharmacokinetics, and Pharmacodynamics in Adult Patients With Cryopyrin-Associated Periodic Syndromes

This is a first in human (FIH), single-centre, double -blind, randomised, cross-over, SAD followed by a MAD study of IZD334 conducted in healthy adult participants as well as an open-label cohort in adult patients with CAPS. The study is designed to evaluate the safety, tolerability, PK, PD, and food effect of IZD334 in healthy adult participants, and to evaluate the safety, tolerability, PK, PD, and preliminary clinical efficacy of IZD334 in adult patients with CAPS.

Start Date13 Sep 2019

Sponsor / Collaborator

Inflazome UK Ltd.

100 Clinical Results associated with IZD-334

100 Translational Medicine associated with IZD-334

100 Patents (Medical) associated with IZD-334

Literatures (Medical) associated with IZD-334

Biomedicines

NLRP3-Inflammasome Inhibition with IZD334 Does Not Reduce Cardiac Damage in a Pig Model of Myocardial Infarction

Article

Author: Demkes, Evelyne J ; Timmers, Leo ; van Hout, Gerardus P J ; Arslan, Fatih ; de Kleijn, Dominique P V ; Bosch, Lena ; de Jager, Saskia C A ; Mosterd, Arend ; Sluijter, Joost P G ; Silvis, Max J M

NLRP3-inflammasome-mediated signaling is thought to significantly contribute to the extent of myocardial damage after myocardial infarction (MI). The purpose of this study was to investigate the effects of the NLRP3-inflammasome inhibitor IZD334 on cardiac damage in a pig model of myocardial infarction. Prior to in vivo testing, in vitro, porcine peripheral blood mononuclear cells and whole blood were treated with increasing dosages of IZD334, a novel NLRP3-inflammasome inhibitor, and were stimulated with lipopolysaccharide (LPS) and adenosine triphosphate (ATP). After determination of the pharmacological profile in healthy pigs, thirty female Landrace pigs were subjected to 75 min of transluminal balloon occlusion of the LAD coronary artery and treated with placebo or IZD334 (1 mg/kg, 3 mg/kg, or 10 mg/kg once daily) in a blinded randomized fashion. In vitro, NLRP3-inflammasome stimulation showed the pronounced release of interleukin (IL)-1β that was attenuated by IZD334 (p < 0.001). In vivo, no differences were observed between groups in serological markers of inflammation nor myocardial IL-1β expression. After 7 days, the ejection fraction did not differ between groups, as assessed with MRI (placebo: 45.1 ± 8.7%, 1 mg/kg: 49.9 ± 6.1%, 3 mg/kg: 42.7 ± 3.8%, 10 mg/kg: 44.9 ± 6.4%, p = 0.26). Infarct size as a percentage of the area at risk was not reduced (placebo: 73.1 ± 3.0%, 1 mg/kg: 75.5 ± 7.3%, 3 mg/kg: 80.3 ± 3.9%, 10 mg/kg: 78.2 ± 8.0%, p = 0.21). In this pig MI model, we did not observe attenuation of the inflammatory response after NLRP3-inflammasome inhibition in vivo. Consecutively, no difference was observed in IS and cardiac function, while in vitro inhibition successfully reduced IL-1β release from stimulated porcine blood cells.

100 Deals associated with IZD-334

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Cardiovascular Diseases	Phase 2	NL	Inflazome Ltd.Startup	08 Aug 2020
Cryopyrin-Associated Periodic Syndromes	Phase 2	AU	Inflazome UK Ltd.	13 Sep 2019

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