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Mult Scler. 2015 Jun;21(7):885-93. doi: 10.1177/1352458514554052. Epub 2014 Nov 12.

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.

Author information

1
Neurology Department, Basel University Hospital, Switzerland.
2
GeNeuro SA, Switzerland fc@geneuro.com.
3
Department of Clinical Neurosciences, Geneva University Hospital, Switzerland.
4
Pharmacology and Toxicology Division, Geneva University Hospital, Switzerland.
5
Neurology Department, Lausanne University Hospital, Switzerland.
6
GeNeuro SA, Switzerland.
7
GeNeuro SA, Switzerland/Pharmacology Department, University of Pretoria, South Africa.
8
Neurology Department, Heinrich Heine University, Germany.
9
Department of Clinical Neurosciences, Geneva University Hospital, Switzerland/Department of Genetic and Laboratory Medicine, Geneva University Hospital, Switzerland/Department of Pathology and Immunology, University of Geneva, Switzerland.

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01639300.

KEYWORDS:

Multiple sclerosis; clinical trial; endogenous retrovirus; human endogenous retrovirus type W family; monoclonal antibody; multiple sclerosis-associated retrovirus

PMID:
25392325
DOI:
10.1177/1352458514554052
[Indexed for MEDLINE]

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