Abstract 19730: First Administration of COR-1 in Man - A Cyclic Peptide Which Neutralizes Anti-β1 Receptor-Antibodies in Heart Failure
Background: A novel concept for the treatment of heart failure is the neutralization of antibodies against the ß 1-adrenergic receptor (Anti-ß 1AR-Ab). In a rat model of autoimmune cardiomyopathy, the cyclic peptide COR-1 (given i.v. once monthly) neutralized Anti-ß 1AR-Ab and prevented and/or treated Anti-ß 1AR-Ab-induced myocardial damage, and completely reverted LV dysfunction over 3 – 6 months.
Objective of the study: A Clinical phase I trial (Eudra-CT 2008–007745-31; NCT 01043146) was designed as a randomized, single blind, placebo-controlled study. 50 male human volunteers between 18 and 45 years received COR-1 or matching placebo intravenously as single intravenous administrations with ascending doses (10 mg to 240 mg). Primary endpoints were safety and tolerability, while the pharmacokinetics profile of COR-1 was assessed as a secondary endpoint.
Results: All five investigated dose groups were well tolerated, no drug-related side effects occurred. Pharmacokinetics revealed a favourable profile with an almost complete serum clearance within 60 minutes after administration. Pharmacodynamic investigation showed dose-dependent efficacy with almost complete scavenging of pathological anti-ß 1 receptor antibodies ex vivo at the two highest doses. No anti-COR-1 auto-antibodies occurred.
Summary: COR-1 was shown to be safe after intravenous administration in vivo, no relevant side effects occurred. Efficacy was estimated from ex vivo investigation of the potency to neutralize specific Anti-ß 1-AR-Ab.
- © 2010 by American Heart Association, Inc.