RT Journal Article
SR Electronic
T1 Randomized phase 1b trial of MOR103, a human antibody to GM-CSF, in multiple sclerosis
JF Neurology - Neuroimmunology Neuroinflammation
JO Neurol Neuroimmunol Neuroinflamm
FD Lippincott Williams & Wilkins
SP e117
DO 10.1212/NXI.0000000000000117
VO 2
IS 4
A1 Cris S. Constantinescu
A1 Aliya Asher
A1 Waldemar Fryze
A1 Wojciech Kozubski
A1 Frank Wagner
A1 Jehan Aram
A1 Radu Tanasescu
A1 Roman P. Korolkiewicz
A1 Maren Dirnberger-Hertweck
A1 Stefan Steidl
A1 Susan E. Libretto
A1 Till Sprenger
A1 Ernst W. Radue
YR 2015
UL http://nn.neurology.org/content/2/4/e117.abstract
AB 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.AE=adverse event; AUCtau=area under the serum concentration vs time curve; DLCO=diffusing capacity of the lung for carbon monoxide; DMC=data monitoring committee; EAE=experimental autoimmune encephalomyelitis; EDSS=Expanded Disability Status Scale; Gd=gadolinium; GM-CSF=granulocyte-macrophage colony-stimulating factor; IFN=interferon; IVIg=IV gamma globulin; IL=interleukin; MS=multiple sclerosis; PFT=pulmonary function test; PK=pharmacokinetics; RRMS=relapsing-remitting MS; SPMS=secondary progressive MS; SSP-D=serum surfactant protein D; TEAE=treatment-emergent AE