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

Abstract

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

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

“…During the open-label extension, the most frequent AEs were gait disturbance (9 episodes) re-ported by 2 patients in the 2 mg/kg group and 1 patient in the 6 mg/kg group, nasopharyngitis (8 episodes) reported by 3 patients in the 2 mg/kg group and 2 patients in the 6 mg/kg group, and leukocyturia (7 episodes) reported by 1 patient in the 2 mg/kg group and 2 patients in the 6 mg/kg group. During the extension to 12 months, no new safety findings were observed compared to those reported before (Derfuss et al, 2014). No infusion reactions and no hypersensitivity were observed.…”

“…After repeated administrations over one year, GNbAC1 appears to be safe, with adverse events mainly related to medical conditions of the patients. In particular, extending treatment over one year did not suggest additional safety risks compared to the initial exposure (Curtin et al, 2012;Derfuss et al, 2014) without evidence of hypersensitivity or infusion reaction, and no induction of immunogenicity was observed.…”

“…Second-ary objectives included pharmacokinetics, pharmacodynamics, brain magnetic resonance imaging (MRI), immunogenicity and expanded dis-ability status scale (EDSS) measurements. The design of the trial is described in more details in Derfuss et al (2014). The study protocol was approved by the local ethics committees and the Swiss Medicine Agency, Swissmedic.…”

“…EDSS was assessed at baseline and after the 6th and 12th drug administrations. Methods for GNbAC1 measurement, anti-drug antibody detection and MRI techniques are described else-where (Curtin et al, 2012;Derfuss et al, 2014). Descriptive statistics were computed for the pharmacokinetic, safety, and pharmacodynamic data using SAS® Version 9.2 (SAS Institute, Cary, NC, USA).…”

“…GNbAC1 had been studied first in a phase I clinical trial in 33 healthy subjects, showing a good safety as well as a linear pharmacokinetics (Curtin et al, 2012). The goals of the present placebo controlled dose escalation study with an open-label extension was to assess the safety profile, immunogenicity, pharmacokinetic parameters and pharmacodynamics of repeated administrations of GNbAC1 at doses of 2 and 6 mg/kg in MS patients (Derfuss et al, 2014). The results of the open-label extension phase up to 12 months of treatment are presented.…”