title: Serum pharmacokinetics and cerebrospinal fluid concentration analysis of the new IgG4 monoclonal antibody GNbAC1 to treat multiple sclerosis: A Phase 1 study.
abstract: GNbAC1 is a humanized IgG4 monoclonal antibody antagonist of Mulitple Sclerosis Retrovirus Envelope (MSRV-Env), a protein that could play a critical role in multiple sclerosis. This randomized placebo-controlled dose-escalation study evaluated the safety and pharmacokinetics of GNbAC1 in 21 healthy volunteers after single intravenous infusion at doses of 6, 18 and 36 mg/kg. Lumbar punctures were performed at days 2, 15 or 29 to measure GNbAC1 concentrations in cerebrospinal fluid (CSF). GNbAC1 was well tolerated. Serum data show a dose-linear pharmacokinetics. A mean CSF/serum ratio of 0.12% was observed at Day 2, increasing to 0.39% at Day 15 and 0.42% at Day 29. Linear regression analysis shows a relationship between GNbAC1 CSF/serum ratio and albumin CSF/serum ratio and a relationship at the limit of statistical significance with the timing of CSF sampling.
authors.affiliation: a GeNeuro SA, Chemin des Aulx 18 , Plan-les-Ouates/Geneva , Switzerland.|b Division of Clinical Pharmacology and Toxicology, Rue Perret-Gentil, University of Geneva , Geneva , Switzerland.
authors.forename: François
authors.initials: F
authors.lastname: Curtin
authors.affiliation: a GeNeuro SA, Chemin des Aulx 18 , Plan-les-Ouates/Geneva , Switzerland.
authors.forename: Virginie
authors.initials: V
authors.lastname: Vidal
authors.affiliation: a GeNeuro SA, Chemin des Aulx 18 , Plan-les-Ouates/Geneva , Switzerland.
authors.forename: Corinne
authors.initials: C
authors.lastname: Bernard
authors.affiliation: c IPM Biotech GmbH , Lademannbogen 61, Hamburg , Germany.
authors.forename: Arno
authors.initials: A
authors.lastname: Kromminga
authors.affiliation: a GeNeuro SA, Chemin des Aulx 18 , Plan-les-Ouates/Geneva , Switzerland.
authors.forename: Alois B
authors.initials: AB
authors.lastname: Lang
authors.affiliation: a GeNeuro SA, Chemin des Aulx 18 , Plan-les-Ouates/Geneva , Switzerland.|d Department of Pharmacology , University of Pretoria , Pretoria , South Africa.
authors.forename: Hervé
authors.initials: H
authors.lastname: Porchet
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C581064:temelimab
keywords: Cerebrospinal fluid; clinical trial; monoclonal antibody; multiple sclerosis; pharmacokinetics; safety