A Phase 3 Prospective, Blinded, Randomized, Placebo Controlled, International Multicenter Study to Assess the Safety and Efficacy of a Single SQ Injection of Zalunfiban in Subjects With ST-elevation MI in the Pre-hospital Setting

This is a Phase 3 prospective, blinded, randomized, placebo controlled, international multicenter study. Subjects with STEMI will be enrolled in the ambulance if they meet all eligibility criteria. These subjects will be evaluated by (para)medics who transport the subjects to the participating hospitals in Europe and North America. Hospitals and ambulance services with experience in ambulance studies will be selected. Each subject will receive a single subcutaneous injection containing either zalunfiban Dose 1 (0.110 mg/kg) or zalunfiban Dose 2 (0.130 mg/kg) or placebo

Start Date24 Apr 2021

Sponsor / Collaborator

CeleCor Therapeutics, Inc.Startup

NCT04284995 / CompletedPhase 2

A Phase 2 Open Label Study to Assess the PK and PD Properties of a Single Subcutaneous Injection of RUC-4 in Patients With a ST-elevation Myocardial Infarction Presenting to the Cardiac Catheterization Lab With Planned Primary Coronary Angioplasty

RUC-4 is a novel, promising and fast acting (5-15 minutes) αIIbβ3 receptor antagonist with a high-grade inhibition of platelet aggregation (≥80%) shortly after subcutaneous administration. This study is designed to extend the findings in CEL-01 to patients with ST-elevation myocardial Infarction (STEMI) presenting to the cardiac catheterization laboratory with planned coronary angioplasty.

Start Date02 Jun 2020

Sponsor / Collaborator

CeleCor Therapeutics, Inc.Startup

[+2]

NCT03844191 / CompletedPhase 1

A Randomized Phase 1 Dose-Escalation Study in Healthy Volunteers and Subjects on Aspirin With Stable Coronary Artery Disease to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneous RUC-4

This study is designed to assess tolerability of the weight-adjusted dose of RUC-4 (mg/kg) required to achieve 80% or more inhibition of the initial slope of platelet aggregation to 20 µM ADP by Light Transmission Aggregometry (LTA) within 15 minutes of SC administration of RUC-4 with return toward baseline values within 4 hours in healthy volunteers and subjects on aspirin with stable coronary artery disease (CAD). In the Dose Expansion Part, VerifyNow PRUTest will be used to measure platelet aggregation in addition to LTA.
Since the goal of RUC-4 therapy is to achieve maximal antiplatelet therapy as rapidly as possible, first the tolerability of the weight-adjusted dose (mg/kg) that inhibits ADP-induced platelet aggregation by 80% or more in 5 of 6 healthy volunteers will be identified. A similar dose escalation will be subsequently performed in subjects with CAD who are taking aspirin. To facilitate administration using a single weight-adjusted (mg/kg) dose for a defined group of subjects weighing between 55 and 120 kg, the study will also evaluate the safety and biologic effect on platelet aggregation of the weight adjusted (mg/kg) dose when administered to subjects with weights at either end of this range.

Start Date18 Feb 2019

Sponsor / Collaborator

CeleCor Therapeutics, Inc.Startup

[+3]

100 Clinical Results associated with Zalunfiban

100 Translational Medicine associated with Zalunfiban

100 Patents (Medical) associated with Zalunfiban

Literatures (Medical) associated with Zalunfiban

19 Dec 2023·Journal of the American Heart Association

Critical Analysis of Thrombocytopenia Associated With Glycoprotein IIb/IIIa Inhibitors and Potential Role of Zalunfiban, a Novel Small Molecule Glycoprotein Inhibitor, in Understanding the Mechanism(s)

Review

Author: Coller, Barry S ; Ten Berg, Jurriën M ; Kereiakes, Dean J ; van 't Hof, Arnoud W J ; Rikken, Sem A O F

Thrombocytopenia is a rare but serious complication of the intravenous glycoprotein IIb/IIIa (GPIIb/IIIa; integrin αIIbβ3) receptor inhibitors (GPIs), abciximab, eptifibatide, and tirofiban. The thrombocytopenia ranges from mild (50 000–100 000 platelets/μL), to severe (20 000 to <50 000/μL), to profound (<20 000/μL). Profound thrombocytopenia appears to occur in <1% of patients receiving their first course of therapy. Thrombocytopenia can be either acute (<24 hours) or delayed (up to ~14 days). Both hemorrhagic and thrombotic complications have been reported in association with thrombocytopenia. Diagnosis requires exclusion of pseudothrombocytopenia and heparin‐induced thrombocytopenia. Therapy based on the severity of thrombocytopenia and symptoms may include drug withdrawals and treatment with steroids, intravenous IgG, and platelet transfusions. Abciximab‐associated thrombocytopenia is most common and due to either preformed antibodies or antibodies induced in response to abciximab (delayed). Readministration of abciximab is associated with increased risk of thrombocytopenia. Evidence also supports an immune basis for thrombocytopenia associated with the 2 small molecule GPIs. The latter bind αIIbβ3 like the natural ligands and thus induce the receptor to undergo major conformational changes that potentially create neoepitopes. Thrombocytopenia associated with these drugs is also immune‐mediated, with antibodies recognizing the αIIbβ3 receptor only in the presence of the drug. It is unclear whether the antibody binding depends on the conformational change and whether the drug contributes directly to the epitope. Zalunfiban, a second‐generation subcutaneous small molecule GPI, does not induce the conformational changes; therefore, data from studies of zalunfiban will provide information on the contribution of the conformational changes to the development of GPI‐associated thrombocytopenia.

01 Nov 2023·Journal of thrombosis and thrombolysis

Comparison of the effects of the GPIIb-IIIa antagonist Zalunfiban and the P2Y12 antagonist Selatogrel on Platelet Aggregation.

Article

Author: Jennings, Lisa K ; Curry, Benjamin J ; Granger, Christopher B ; Ten Berg, Jurriën M ; van 't Hof, Arnoud W J ; Rikken, A O F Sem ; Gibson, C Michael

Understanding the pharmacodynamic effects of platelet inhibitors is standard for developing more effective antithrombotic therapies. An example is the antithrombotic treatment of acute coronary syndrome (ACS), in particular ST-elevated myocardial infarction (STEMI) patients who are in need for rapid acting strong antithrombotic therapy despite the use of aspirin and oral P2Y12-inhibitors. In this study, we evaluated two injectable platelet inhibitors under clinical development (the P2Y12 antagonist selatogrel and the GPIIb-IIIa antagonist zalunfiban) that may be amenable to pre-hospital treatment of STEMI patients. Platelet reactivity was assessed at inhibitor concentrations that represent clinically relevant levels of platelet inhibition (IC20-50%, 1/2Cmax, and Cmax). Light transmission aggregometry (LTA), was used to evaluate the initial rate of aggregation (primary slope, PS) and maximal aggregation (MA). Both adenosine diphosphate (ADP) and thrombin receptor agonist peptide (TRAP) were used as agonists. Zalunfiban demonstrated similar inhibition of platelet aggregation when blood was collected in PPACK or TSC, whereas selatogrel demonstrated greater inhibition in PPACK. In this study, using PPACK anticoagulant, selatogrel and zalunfiban affected PS in response to ADP equivalently at all drug concentrations tested. In contrast, zalunfiban had significantly greater potency at its Cmax concentration compared to selatogrel using TRAP as agonist. Upon evaluation of MA responses at lower doses, selatogrel had greater inhibition of MA in response to ADP than zalunfiban; however, at concentrations that represent Cmax, the drugs were equivalent. Zalunfiban also had greater inhibition of MA in response to TRAP at the Cmax dose. These data suggest that zalunfiban may provide greater protection in reducing thrombus formation than selatogrel, especially since thrombin is an early, key primary agonist in the pathophysiology of thrombotic events.

01 Aug 2023·American heart journal

Prepercutaneous coronary intervention Zalunfiban dose-response relationship to target vessel blood flow at initial angiogram in st-elevation myocardial infarction - A post hoc analysis of the cel-02 phase IIa study.

Article

Author: Coller, Barry S ; Hack, Amy P ; van 't Hof, Arnoud W J ; Zheng, Kai L ; Bentur, Ohad S ; Bor, Willem L ; Selvarajah, Abi ; Gibson, C Michael ; Ten Berg, Jurriën M ; Rikken, Sem A O F ; Granger, Christopher B

BACKGROUNDZalunfiban (RUC-4) is a novel, subcutaneously administered glycoprotein IIb/IIIa inhibitor (GPI) designed for prehospital treatment to initiate reperfusion in the infarct-related artery (IRA) before primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction (STEMI). Since GPIs have been reported to rapidly reperfuse IRAs, we assessed whether there was a dose-dependent relationship between zalunfiban treatment and angiographic reperfusion indices and thrombus grade of the IRA at initial angiogram in patients with STEMI.METHODSThis was a post hoc analysis from the open-label Phase IIa study that investigated the pharmacodynamics, pharmacokinetics, and tolerability of three doses of zalunfiban - 0.075, 0.090 and 0.110 mg/kg - in STEMI patients. This analysis explored dose-dependent associations between zalunfiban and three angiographic indices of the IRA, namely coronary and myocardial blood flow and thrombus burden. Zalunfiban was administered in the cardiac catheterization laboratory prior to vascular access, ∼10 to 15 minutes before the initial angiogram. All angiographic data were analyzed by a blinded, independent, core laboratory.RESULTSTwentyfour out of 27 STEMI patients were evaluable for angiographic analysis (0.075 mg/kg [n=7], 0.090 mg/kg [n=9], and 0.110 mg/kg [n=8]). TIMI flow grade 2 or 3 was seen in 1/7 patients receiving zalunfiban at 0.075 mg/kg, in 6/9 patients receiving 0.090 mg/kg, and in 7/8 patients receiving 0.110 mg/kg (p_trend = 0.004). A similar trend was observed based on TIMI flow grade 3. Myocardial perfusion was also related to zalunfiban dose (p_trend = 0.005) as reflected by more frequent TIMI myocardial perfusion grade 3. Consistent with the dose-dependent trends in greater coronary and myocardial perfusion, TIMI thrombus ≥4 grade was inversely related to zalunfiban dose (p_trend = 0.02).CONCLUSIONThis post hoc analysis found that higher doses of zalunfiban administered in the cardiac catheterization lab prior to vascular access were associated with greater coronary and myocardial perfusion, and lower thrombus burden at initial angiogram in patients with STEMI undergoing primary percutaneous coronary intervention.

100 Deals associated with Zalunfiban

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Indication	Highest Phase	Country/Location	Organization	Date
ST Elevation Myocardial Infarction	Phase 3	FR	CeleCor Therapeutics, Inc.Startup	24 Apr 2021
ST Elevation Myocardial Infarction	Phase 3	CZ	CeleCor Therapeutics, Inc.Startup	24 Apr 2021
ST Elevation Myocardial Infarction	Phase 3	HU	CeleCor Therapeutics, Inc.Startup	24 Apr 2021
ST Elevation Myocardial Infarction	Phase 3	CA	CeleCor Therapeutics, Inc.Startup	24 Apr 2021
ST Elevation Myocardial Infarction	Phase 3	NL	CeleCor Therapeutics, Inc.Startup	24 Apr 2021
ST Elevation Myocardial Infarction	Phase 3	RO	CeleCor Therapeutics, Inc.Startup	24 Apr 2021
Coronary Artery Disease	Phase 1	-	The Rockefeller University	-
Coronary Disease	Discovery	NL	CeleCor Therapeutics, Inc.Startup	02 Jun 2020

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04825743 (CELEBRATE, ESC2022)	Phase 2	ST Elevation Myocardial Infarction	27	Zalunfiban	(yfkxdjthhg) = wylevzwjzh pvkzhehwek (vbcsdknqpv )	-	18 Mar 2022
ISTH2021	Phase 1	ST Elevation Myocardial Infarction	-	RUC-4 (Zalunfiban)	akczcepmvh(ukqomlbwpb) = hwfsifiick wlyfkdveps (nyizdxsqwa )	-	17 Jul 2021

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