A phase IIa randomized clinical study testing GNbAC1, a humanized monoclonal antibody against the envelope protein of multiple sclerosis associated endogenous retrovirus in multiple sclerosis patients - a twelve month follow-up

Tobias Derfuss; François Curtin; Claudia Guebelin; Claire Bridel; Maria Rasenack; Alain Matthey; Renaud Du Pasquier; Myriam Schluep; Jules Desmeules; Alois B Lang; Hervé Perron; Raphael Faucard; Hervé Porchet; Hans-Peter Hartung; Ludwig Kappos; Patrice H Lalive

doi:10.1016/j.jneuroim.2015.05.019

A phase IIa randomized clinical study testing GNbAC1, a humanized monoclonal antibody against the envelope protein of multiple sclerosis associated endogenous retrovirus in multiple sclerosis patients - a twelve month follow-up

J Neuroimmunol. 2015 Aug 15:285:68-70. doi: 10.1016/j.jneuroim.2015.05.019. Epub 2015 May 20.

Authors

Tobias Derfuss¹, François Curtin², Claudia Guebelin¹, Claire Bridel³, Maria Rasenack¹, Alain Matthey⁴, Renaud Du Pasquier⁵, Myriam Schluep⁵, Jules Desmeules⁴, Alois B Lang⁶, Hervé Perron⁶, Raphael Faucard⁶, Hervé Porchet⁷, Hans-Peter Hartung⁸, Ludwig Kappos¹, Patrice H Lalive⁹

Affiliations

¹ Neurology Department, Basel University Hospital, Petersgraben 4, Basel, Switzerland.
² GeNeuro SA, Chemin des Aulx 18, CH 1228 Plan-les-Ouates, Geneva, Switzerland. Electronic address: [email protected].
³ Department of Clinical Neurosciences, Division of Neurology, Unit of Neuroimmunology and Multiple Sclerosis, Geneva University Hospital, 1211 Geneva, Switzerland.
⁴ Pharmacology and Toxicology Division & Clinical Trial Unit, Geneva University Hospital, Rue Gabrielle Perret-Gentil, 1214 Geneva, Switzerland.
⁵ Neurology Department, Lausanne University Hospital, Rue du Bugnon 46, 1011 Lausanne, Switzerland.
⁶ GeNeuro SA, Chemin des Aulx 18, CH 1228 Plan-les-Ouates, Geneva, Switzerland.
⁷ GeNeuro SA, Chemin des Aulx 18, CH 1228 Plan-les-Ouates, Geneva, Switzerland; Pharmacology Department, University of Pretoria, South Africa.
⁸ Neurology Department, Heinrich Heine University, Moorenstrasse 5, D-40225 Düsseldorf, Germany.
⁹ Department of Clinical Neurosciences, Division of Neurology, Unit of Neuroimmunology and Multiple Sclerosis, Geneva University Hospital, 1211 Geneva, Switzerland; Department of Genetic and Laboratory Medicine, Division of Laboratory Medicine, Geneva University Hospital, 1211 Geneva, Switzerland; Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.

PMID: 26198921
DOI: 10.1016/j.jneuroim.2015.05.019

Abstract

GNbAC1 is a humanized monoclonal antibody targeting MSRV-Env, an endogenous retroviral protein, which is expressed in multiple sclerosis (MS) lesions, is pro-inflammatory and inhibits oligodendrocyte precursor cell differentiation. This paper describes the open-label extension up to 12months of a trial testing GNbAC1 in 10 MS patients at 2 and 6mg/kg. The primary objective was to assess GNbAC1 safety, and other objectives were pharmacokinetic and pharmacodynamic assessments. During the extended study, no safety issues occurred in the 8 remaining patients. No anti-GNbAC1 antibodies were detected. GNbAC1 appears well tolerated.

Keywords: Clinical trial; Human endogenous retrovirus; Monoclonal antibody; Multiple sclerosis; Safety.

Publication types

Clinical Trial, Phase II
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Antibodies, Monoclonal, Humanized / pharmacology
Antibodies, Monoclonal, Humanized / therapeutic use*
Cohort Studies
Endogenous Retroviruses / drug effects*
Endogenous Retroviruses / immunology
Female
Follow-Up Studies
Humans
Male
Middle Aged
Multiple Sclerosis / drug therapy*
Multiple Sclerosis / immunology
Viral Envelope Proteins / antagonists & inhibitors*
Viral Envelope Proteins / immunology

Substances

Antibodies, Monoclonal, Humanized
Viral Envelope Proteins
temelimab