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A Randomized, First‐in‐Human, Healthy Volunteer Trial of sutimlimab, a Humanized Antibody for the Specific Inhibition of the Classical Complement Pathway
Author(s) -
Bartko Johann,
Schoergenhofer Christian,
Schwameis Michael,
Firbas Christa,
Beliveau Martin,
Chang Colin,
Marier JeanFrancois,
Nix Darrell,
Gilbert James C.,
Panicker Sandip,
Jilma Bernd
Publication year - 2018
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.1111
Subject(s) - medicine , autoimmune hemolytic anemia , alternative complement pathway , pharmacokinetics , complement system , immunology , pharmacology , antibody , pharmacodynamics , classical complement pathway , placebo , complement deficiency , humanized antibody , monoclonal antibody , complement component 5 , pathology , alternative medicine
Aberrant activation of the classical complement pathway is the common underlying pathophysiology of orphan diseases such as bullous pemphigoid, antibody‐mediated rejection of organ transplants, cold agglutinin disease, and warm autoimmune hemolytic anemia. Therapeutic options for these complement‐mediated disorders are limited and sutimlimab, a humanized monoclonal antibody directed against complement factor C1s, may be potentially useful for inhibition of the classical complement pathway. A phase I, first‐in‐human, double‐blind, randomized, placebo‐controlled, dose‐escalation trial of single and multiple doses of sutimlimab or placebo was conducted in 64 volunteers to evaluate safety, tolerability, pharmacokinetic, and pharmacodynamic profiles. Single and multiple infusions of sutimlimab were well tolerated without any safety concerns. sutimlimab exhibited a steep concentration–effect relationship with a Hill coefficient of 2.4, and an IC 90 of 15.5 μg/mL. This study establishes the foundation for using sutimlimab as a highly selective inhibitor of the classical complement pathway in different diseases.