title: Complete Removal of Extracellular IgG Antibodies in a Randomized Dose-Escalation Phase I Study with the Bacterial Enzyme IdeS--A Novel Therapeutic Opportunity.
abstract: IdeS is a streptococcal protease that cleaves IgG antibodies into F(ab’)2 and Fc fragments with a unique degree of specificity, thereby providing a novel treatment opportunity of IgG-driven autoimmune conditions and antibody mediated transplant rejection. Here we report the results from a first in man, double blinded and randomized study with single ascending doses of IdeS in healthy, male subjects. Twenty healthy subjects were given intravenous single ascending doses of IdeS. With impressive efficacy IdeS cleaved the entire plasma IgG-pool only minutes after dosing. IgG reached nadir 6-24 hours after dosing and then slowly recovered. The half-life of IdeS was 4.9 (±2.8) hours at 0.24 mg/kg with the main fraction eliminated during 24 hours. Already two hours after IdeS-dosing, the phagocytic capacity of IgG/IgG-fragments was reduced to background levels. Importantly, IdeS has the capacity to inactivate Fc-mediated effector function in vivo, was considered safe with no serious adverse events, and without dose limiting toxicity in this study. The complete, rapid, but temporary removal of IgG provides a new potent therapeutic opportunity in IgG-mediated pathogenic conditions.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01802697.
authors.affiliation: Hansa Medical AB, Scheelevägen 22, P.O. Box 785, SE-22007 Lund, Sweden.
authors.forename: Lena
authors.initials: L
authors.lastname: Winstedt
authors.affiliation: Hansa Medical AB, Scheelevägen 22, P.O. Box 785, SE-22007 Lund, Sweden.
authors.forename: Sofia
authors.initials: S
authors.lastname: Järnum
authors.affiliation: Hansa Medical AB, Scheelevägen 22, P.O. Box 785, SE-22007 Lund, Sweden.
authors.forename: Emma Andersson
authors.initials: EA
authors.lastname: Nordahl
authors.affiliation: Hansa Medical AB, Scheelevägen 22, P.O. Box 785, SE-22007 Lund, Sweden.
authors.forename: Andreas
authors.initials: A
authors.lastname: Olsson
authors.affiliation: Hansa Medical AB, Scheelevägen 22, P.O. Box 785, SE-22007 Lund, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Runström
authors.affiliation: Hansa Medical AB, Scheelevägen 22, P.O. Box 785, SE-22007 Lund, Sweden.
authors.forename: Robert
authors.initials: R
authors.lastname: Bockermann
authors.affiliation: Department of Clinical Sciences, Lund, Lund University, SE-221 84 Lund, Sweden.
authors.forename: Christofer
authors.initials: C
authors.lastname: Karlsson
authors.affiliation: Department of Clinical Sciences, Lund, Lund University, SE-221 84 Lund, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Malmström
authors.affiliation: Clinical Trials Unit, Skåne University Hospital, Lund, Sweden.
authors.forename: Gabriella Samuelsson
authors.initials: GS
authors.lastname: Palmgren
authors.affiliation: Clinical Trials Unit, Skåne University Hospital, Lund, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: Malmqvist
authors.affiliation: Department of Clinical Sciences, Lund, Lund University, SE-221 84 Lund, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Björck
authors.affiliation: Hansa Medical AB, Scheelevägen 22, P.O. Box 785, SE-22007 Lund, Sweden.
authors.forename: Christian
authors.initials: C
authors.lastname: Kjellman
mesh_terms: D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005110:Extracellular Space / Q000737:chemistry*; D006801:Humans; D007074:Immunoglobulin G / Q000302:isolation & purification*; D008297:Male; D010587:Phagocytosis / Q000187:drug effects; D011507:Proteinuria / Q000175:diagnosis; D059748:Proteolysis / Q000187:drug effects
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D007074:Immunoglobulin G; C442815:Mac-1-like protein, Streptococcus