Serum pharmacokinetics and cerebrospinal fluid concentration analysis of the new IgG4 monoclonal antibody GNbAC1 to treat multiple sclerosis: A Phase 1 study. Issue 5 (3rd July 2016)

• Record Type: Journal Article
• Authors: Curtin, François; Vidal, Virginie; Bernard, Corinne; Kromminga, Arno; Lang, Alois B.; Porchet, Hervé
• Is Part Of: MAbs. Volume 8:Issue 5(2016)
• Page Start: 854
• Page End: 860
• Publication Date: 2016-07-03
• Subjects: Cerebrospinal fluid -- clinical trial -- monoclonal antibody -- multiple sclerosis -- pharmacokinetics -- safety; Monoclonal antibodies -- Therapeutic use -- Periodicals; Monoclonal antibodies -- Periodicals; Antibodies, Monoclonal -- Periodicals; 616.0798
• DOI: 10.1080/19420862.2016.1168956
• Languages: English
• ISSNs: 1942-0862

Abstract

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.