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.