Principal Investigator: Robert Goggs

DESCRIPTION (provided by applicant): 

Immune-mediated hemolytic anemia (IMHA) is a common disease that affects all breeds of dogs and is associated with significant morbidity and mortality. Intravascular hemolysis of erythrocytes in IMHA is caused by complement activation and is often fatal. No current treatments target complement activation in canine IMHA. Our preliminary data show that human C1 esterase (C1- INH) reduces canine complement-mediated hemolysis by more than 80% in vitro. We recently completed an MAF sponsored pharmacokinetic analysis of an FDA licensed formulation of C1-INH, Ruconest in dogs. This confirmed that a 50IU/kg dose of C1-INH is safe to administer to dogs, and effectively inhibits canine complement mediated hemolysis ex-vivo. We expect that intravenous (IV) administration of C1-INH will ablate complement activation in dogs with intravascular IMHA and propose to evaluate the efficacy of this drug in a randomized controlled trial (RCT).

We hypothesize that intravenous C1-INH reduces intravascular hemolysis in dogs with IMHA Our objectives are: 1) To assess efficacy of C1-INH for management of intravascular IMHA in dogs, 2) To assess the frequency of adverse drug reactions to intravenous C1-INH.

We anticipate that IV administration of C1-INH will significantly inhibit complement mediated hemolysis in dogs with intravascular IMHA, as determined by blood biomarker measurements (decreased plasma hemoglobin, LDH and bilirubin, increased haptoglobin). We expect this will translate into significant reductions in transfusion requirements and duration of hospitalization.