Randomized phase 1b trial of MOR103, a human antibody to GM-CSF, in multiple sclerosis

Constantinescu, Cris S.; Asher, Aliya; Fryze, Waldemar; Kozubski, Wojciech; Wagner, Frank; Aram, Jehan; Tanasescu, Radu; Korolkiewicz, Roman P.; Dirnberger-Hertweck, Maren; Steidl, Stefan; Libretto, Susan E.; Sprenger, Till; Radue, Ernst W.

Abstract

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.

Citation

Constantinescu, C. S., Asher, A., Fryze, W., Kozubski, W., Wagner, F., Aram, J., …Radue, E. W. (2015). Randomized phase 1b trial of MOR103, a human antibody to GM-CSF, in multiple sclerosis. Neurology, Neuroimmunology and Neuroinflammation, 2(4), Article e117. https://doi.org/10.1212/nxi.0000000000000117

• Journal Article Type: Article
• Acceptance Date: Apr 22, 2015
• Online Publication Date: May 21, 2015
• Publication Date: 2015-08
• Deposit Date: Nov 25, 2020
• Publicly Available Date: Dec 11, 2020
• Journal: Neurology - Neuroimmunology Neuroinflammation
• Publisher: Lippincott, Williams & Wilkins
• Peer Reviewed: Peer Reviewed
• Volume: 2
• Issue: 4
• Article Number: e117
• DOI: https://doi.org/10.1212/nxi.0000000000000117
• Public URL: https://nottingham-repository.worktribe.com/output/5070557
• Publisher URL: https://nn.neurology.org/content/2/4/e117