calca-protein--human and Ehlers-Danlos-Syndrome

LBR-101 is a fully humanized monoclonal antibody that binds to calcitonin gene-related peptide.. The objective of this article is to characterize the safety and tolerability of LBR-101 when administered intravenously to healthy volunteers, by presenting the pooled results of the Phase 1 program.. LBR-101 was administered to 94 subjects, while 45 received placebo. Doses ranged from 0.2 mg to 2000 mg given once (Day 1), as a single IV infusion, or up to 300 mg given twice (Day 1 and Day 14).. Subjects receiving placebo reported an average of 1.3 treatment-emerging adverse events vs 1.4 per subject among those receiving any dose of LBR-101, and 1.6 in those receiving 1000 mg or higher. Treatment-related adverse events occurred in 21.2% of subjects receiving LBR-101, compared to 17.7% in those receiving placebo. LBR-101 was not associated with any clinically relevant patterns of change in vital signs, ECG parameters, or laboratory findings. The only serious adverse event consisted of "thoracic aortic aneurysm" in a participant later found to have an unreported history of Ehlers-Danlos syndrome.. Single IV doses of LBR-101 ranging from 0.2 mg up to 2000 mg and multiple IV doses up to 300 mg were well tolerated. Overt safety concerns have not emerged. A maximally tolerated dose has not been identified.

Topics: Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Aged; Antibodies, Monoclonal; Aortic Aneurysm, Thoracic; Calcitonin Gene-Related Peptide; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Ehlers-Danlos Syndrome; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Young Adult