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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

Derfuss, T. and Curtin, F. and Guebelin, C. and Bridel, C. and Rasenack, M. and Matthey, A. and Du Pasquier, R. and Schluep, M. and Desmeules, J. and Lang, A. B. and Perron, H. and Faucard, R. and Porchet, H. and Hartung, H. P. and Kappos, L. and Lalive, P. H.. (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 Journal, 21 (7). pp. 885-893.

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Official URL: https://edoc.unibas.ch/61683/

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Abstract

BACKGROUND: 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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Clinical Neuroimmunology (Derfuss/Lindberg)
UniBasel Contributors:Derfuss, Tobias Johannes
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Sage Publications
ISSN:1352-4585
e-ISSN:1477-0970
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:01 Nov 2018 18:18
Deposited On:16 Oct 2018 17:14

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