title: Safety and tolerability of LBR-101, a humanized monoclonal antibody that blocks the binding of CGRP to its receptor: Results of the Phase 1 program.
abstract: BACKGROUND
  LBR-101 is a fully humanized monoclonal antibody that binds to calcitonin gene-related peptide.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Labrys Biologics Inc., CA, USA mbigal@labrysbiologics.com.
authors.forename: Marcelo E
authors.initials: ME
authors.lastname: Bigal
authors.affiliation: Labrys Biologics Inc., CA, USA.
authors.forename: Rafael
authors.initials: R
authors.lastname: Escandon
authors.affiliation: Labrys Biologics Inc., CA, USA.
authors.forename: Michele
authors.initials: M
authors.lastname: Bronson
authors.affiliation: Pfizer, Sandwich, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Walter
authors.affiliation: Pfizer, Sandwich, UK.
authors.forename: Maria
authors.initials: M
authors.lastname: Sudworth
authors.affiliation: Pfizer, Sandwich, UK.
authors.forename: John P
authors.initials: JP
authors.lastname: Huggins
authors.affiliation: Pfizer WRD, CA, USA.
authors.forename: Pamela
authors.initials: P
authors.lastname: Garzone
mesh_terms: D000293:Adolescent; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use*; D017545:Aortic Aneurysm, Thoracic / Q000139:chemically induced; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004535:Ehlers-Danlos Syndrome / Q000150:complications; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; C000606589:CALCA protein, human; D015740:Calcitonin Gene-Related Peptide
keywords: CGRP; LBR-101; Monoclonal antibodies; chronic migraine