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Randomized phase 1b trial of MOR103, a human antibody to GM-CSF, in multiple sclerosis
Cris S Constantinescu1, Aliya Asher1, Waldemar Fryze1
1Division of Clinical Neuroscience (C.S.C., J.A., R.T.), Research Group in Clinical Neurology, University of Nottingham, Queen's Medical Centre, Nottingham, UK; MAC Clinical Research Ltd. (A.A.), Trafford Park, Manchester, UK; Pomorskie Centrum Traumatologii im. M. Kopernika w Gdańsku (W.F.), Oddzial Neurologiczny i Udarowy, Gdańsk, Poland; Oddział Kliniczny Neurologii (W.K.), Medical University of Poznan, Poznań, Poland; Charité Research Organisation GmbH (F.W.), Berlin, Germany; MorphoSys AG (R.P.K., M.D.-H., S.S.), Martinsried/Planegg, Germany; Sue Libretto Publications Consultant Ltd. (S.E.L.), Windlesham, Surrey, UK; and MIAC AG (T.S., E.W.R.) and Department of Neurology (T.S.), University Hospital Basel, Basel, Switzerland.
Objectives:
To determine the safety, pharmacokinetics (PK), and immunogenicity of the recombinant human monoclonal antibody MOR103 to granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with multiple sclerosis (MS) with clinical or MRI activity.
Methods:
In this 20-week, randomized, double-blind, placebo-controlled phase 1b dose-escalation trial (registration number NCT01517282), adults with relapsing-remitting MS (RRMS) or secondary progressive MS (SPMS) received an IV infusion of placebo (n = 6) or MOR103 0.5 (n = 8), 1.0 (n = 8), or 2.0 (n = 9) mg/kg every 2 weeks for 10 weeks. Patients had to have ≤10 gadolinium (Gd)-enhancing brain lesions on T1-weighted MRI at baseline. The primary objective was safety.
Results:
Most treatment-emergent adverse events (TEAEs) were mild to moderate in severity. The most frequent was nasopharyngitis. Between-group differences in TEAE numbers were small. There were no TEAE-related trial discontinuations, infusion-related reactions, or deaths. Nine patients experienced MS exacerbations: 3, 5, 1, and 0 patient(s) in the placebo, 0.5, 1.0, and 2.0 mg/kg groups, respectively. A few T1 Gd-enhancing lesions and/or new or enlarging T2 lesions indicative of inflammation were observed in all treatment groups. No clinically significant changes were observed in other clinical assessments or laboratory safety assessments. No anti-MOR103 antibodies were detected. PK evaluations indicated dose linearity with low/no drug accumulation over time.
Conclusions:
MOR103 was generally well-tolerated in patients with RRMS or SPMS. No evidence of immunogenicity was found.
Classification Of Evidence:
This phase 1b study provides Class I evidence that MOR103 has acceptable tolerability in patients with MS.
