Derfuss, TobiasCurtin, FrançoisGuebelin, ClaudiaBridel, ClaireRasenack, MariaMatthey, AlainDu Pasquier, RenaudSchluep, MyriamDesmeules, JulesLang, Alois B.Perron, HervéFaucard, RaphaelPorchet, HervéHartung, Hans-PeterKappos, LudwigLalive, Patrice H.2015-07-142015-07-142015-06Derfuss, T, Curtin, F, Guebelin, C, Bridel, C, Rasenack, M, Matthey, A, Du Pasquier, R, Schluep, M, Desmeules, J, Lang, AB, Perron, H, Faucard, R, Porchet, H, Hartung, HP, Kappos, L & Lalive, PH 2015, 'A phase IIa randomised clinical study of GNbAC1, a humanised monoclonal antibody against the envelope protein of multiple sclerosis-associated endogenous retrovirus in multiple sclerosis patients', Multiple Sclerosis, vol. 21, no. 7, pp. 885-893.1352-4585 (print)1477-0970 (online)10.1177/1352458514554052http://hdl.handle.net/2263/48667BACKGROUND : GNbAC1 is an immunoglobulin (IgG4) humanised monoclonal antibody against multiple sclerosis-associated retrovirus (MSRV)-Env, a protein of endogenous retroviral origin, expressed in multiple sclerosis (MS) lesions, which is pro-inflammatory and inhibits oligodendrocyte precursor cell differentiation. OBJECTIVE : This is a randomised, double-blind placebo-controlled dose-escalation study followed by a six-month open-label phase to test GNbAC1 in MS patients. The primary objective was to assess GNbAC1 safety in MS patients, and the other objectives were pharmacokinetic and pharmacodynamic assessments. METHODS : Ten MS patients were randomised into two cohorts to receive a single intravenous infusion of GNbAC1/placebo at doses of 2 or 6 mg/kg. Then all patients received five infusions of GNbAC1 at 2 or 6 mg/kg at four-week intervals in an open-label setting. Safety, brain magnetic resonance imaging (MRI), pharmacokinetics, immunogenicity, cytokines and MSRV RNA expression were studied. RESULTS : All patients completed the study. GNbAC1 was well tolerated in all patients. GNbAC1 pharmacokinetics is dose-linear with mean elimination half-life of 27–37 d. Anti-GNbAC1 antibodies were not detected. Cytokine analysis did not indicate an adverse effect. MSRV-transcripts showed a decline after the start of treatment. Nine patients had stable brain lesions at MRI. CONCLUSION : The safety, pharmacokinetic profile, and pharmacodynamic responses to GNbAC1 are favourable in MS patients over a six-month treatment period.en© 2015 by Sage PublicationsEndogenous retrovirusHuman endogenous retrovirus (HERV)Monoclonal antibody (MAb)Clinical trialMultiple sclerosis (MS)Multiple sclerosis associated retrovirus envelope (MSRVEnv)Postprint Article