Safety, tolerability, and pharmacokinetics/-dynamics of the dipeptidyl peptidase 3-inhibiting antibody Procizumab in a first-in-human trial.

Procizumab was well-tolerated in a small group of healthy males, with no serious adverse events reported and a terminal elimination half-life ranging from 24 to 53 hours depending on the dose.

Summary and findings

This study evaluated the safety, tolerability, and pharmacokinetics of Procizumab (PCZ) in 24 healthy male volunteers. Participants received placebo or one of three doses of PCZ (3 mg/kg, 6 mg/kg, and 12 mg/kg) and were monitored for 24 hours post-administration and at six follow-up visits over 28 days. No serious adverse events were reported, and the pharmacokinetics showed a terminal elimination half-life of 24, 34, and 53 hours across the dosing groups.

Abstract

Dipeptidyl peptidase 3 (DPP3), an aminopeptidase that degrades several key cardiovascular mediators, may induce and exacerbate hemodynamic instability during cardiogenic shock. Procizumab (PCZ) is a first-in-class humanized monoclonal antibody that inhibits DPP3 activity. In preclinical shock models, PCZ increased angiotensin metabolite levels, improved cardiovascular function, and increased survival. Here, results are presented for a first-in-human Phase 1 trial (NCT06331884) that evaluated the safety, tolerability, and pharmacokinetics and pharmacodynamics of PCZ. Twenty-four healthy male volunteers were enrolled in a randomized, double-blind, placebo-controlled Phase 1 trial. Participants (<i>n</i> = 6 per group) received placebo or one of three doses of PCZ (3 mg/kg, 6 mg/kg, and 12 mg/kg). Participants were monitored clinically for 24 h after drug administration, as well as at 6 follow-up visits performed during a 28-d period. Adverse events associated with PCZ were predominantly mild, and no serious adverse events were reported. Local tolerability, vital signs, laboratory assessments, and electrocardiograms did not reveal any safety concerns. PCZ exhibited a terminal elimination half-life of 24, 34, and 53 h in the low, intermediate, and high-dose groups, respectively. A volume of distribution of roughly 9.8-10.2 liters indicates that the drug predominantly remains within the circulation. Results of this trial are currently being followed up in the PROCARD Phase 1b/2a (NCT06832722) study, which is evaluating safety and determining the optimal dose of PCZ in cardiogenic shock patients.

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