High Dose Clinical Pharmacology Study of GNBAC1, a Humanized Monoclonal Antibody for Multiple Sclerosis (P3.048)

Objective: to assess safety and pharmacology of GNbAC1 a humanized monoclonal antibody Background: MSRV-Env is a protein of endogenous retroviral origin. This protein is expressed in active brain lesions of multiple sclerosis (MS) patients. Due to its pro-inflammatory and myelinotoxic effects, MSRV-Env appears as a pertinent target in MS. GNbAC1 is an IgG4 humanized monoclonal antibody (mAB) which neutralizes MSRV-Env and prevents cytokine release and the nitrosative stress process at the OPC level. Design: This randomized placebo-controlled dose-escalation study evaluated the safety and pharmacokinetics in the plasma and cerebro-spinal fluid (CSF) of GNbAC1 in 21 healthy volunteers at doses of 6, 18, 36 mg/kg. Lumbar punctures were performed at Days 2, 15 and 29 post-infusion. Results: All subjects completed the study. GNbAC1 was well tolerated. All adverse events were mild or moderate in severity. No subject was withdrawn as a result of adverse events. There were no notable dose or treatment related trends in the number or type of adverse events. Pharmacokinetic data show a dose-linear pharmacokinetics in the plasma with half-life ranging from 21.5 to 25.3 days. The concentration of GNbAC1 in CSF was assessed after intravenous infusion at Day 2, 15, and 29. A CSF/plasma ratio of 0.13[percnt] was observed at Day 2 increasing to 0.36[percnt] at Day 15 and 0.28[percnt] at Day 29. The pharmacokinetic profile of GNbAC1 in the CSF shows a progressive increase in this compartment up to an equilibrium. Conclusion: These CSF pharmacokinetic data show that the brain penetration of GNbAC1 is in line with data from other mABs and sufficient to neutralize the MSRV-Env target expressed in brain lesions. These favourable results pave the way to launch a Phase IIb trial testing GNbAC1 in MS patients. Disclosure: Dr. Curtin has received personal compensation for activities with GeNeuro. Dr. Porchet has received personal compensation for activities with Geneuro as an employee. Dr. Lang has received personal compensation for activities with GeNeuro as an employee.