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

Neurology: Neuroimmunology and NeuroInflammation

Volumn 2, Issue 4, 2015, Pages

  Constantinescu, Cris S ^a   Asher, Aliya ^b   Fryze, Waldemar ^c   Kozubski, Wojciech ^d   Wagner, Frank ^e   Aram, Jehan ^a   Tanasescu, Radu ^a   Korolkiewicz, Roman P ^f   Dirnberger Hertweck, Maren ^f   Steidl, Stefan ^f   Libretto, Susan E ^g   Sprenger, Till ^h,i   Radue, Ernst W ^h  

^a UNIVERSITY OF NOTTINGHAM   (United Kingdom)

^b MAC Clinical Research Cobra Court   (United Kingdom)

^c Pomorskie Centrum Traumatologii Im Miko aja Kopernika W Gda sku   (Poland)

^d POZNAN UNIVERSITY OF MEDICAL SCIENCES   (Poland)

^e CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^f MORPHOSYS AG   (Germany)

^g Sue Libretto Publications Consultant Ltd   (United Kingdom)

^h MIAC AG   (Switzerland)

ⁱ UNIVERSITY HOSPITAL BASEL   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

C REACTIVE PROTEIN; GADOLINIUM; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; GSK 3196165; PLACEBO;

ADULT; ARTHRALGIA; ARTICLE; BACKACHE; BLURRED VISION; BONE PAIN; BRAIN DAMAGE; CONTRAST ENHANCEMENT; CONTROLLED STUDY; COUGHING; DIARRHEA; DISEASE EXACERBATION; DISEASE SEVERITY; DOUBLE BLIND PROCEDURE; DRUG ACCUMULATION; DRUG SAFETY; DRUG TOLERABILITY; ENCEPHALITIS; EYE PAIN; FATIGUE; FEMALE; GASTROENTERITIS; HEADACHE; HUMAN; INFECTION; INFUSION RELATED REACTION; LEUKOCYTE COUNT; MAJOR CLINICAL STUDY; MALE; MULTIPLE DRUG DOSE; MULTIPLE SCLEROSIS; MUSCLE TWITCH; NEUROIMAGING; NUCLEAR MAGNETIC RESONANCE IMAGING; PARESTHESIA; PHASE 1 CLINICAL TRIAL; PLASMA CONCENTRATION-TIME CURVE; POLLAKISURIA; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; RANDOMIZED CONTROLLED TRIAL; RHINITIS; RHINOPHARYNGITIS; SENSORY DYSFUNCTION; SIDE EFFECT; TREATMENT DURATION; URINARY TRACT INFECTION; VIBRATION SENSE; VISUAL ACUITY;

EID: 84953275929     PISSN: None     EISSN: 23327812     Source Type: Journal    
DOI: 10.1212/NXI.0000000000000117     Document Type: Article

References (18)

1. Waubant E. Overview of treatment options in multiple sclerosis. J Clin Psychiatry 2012; 73:e22.
2. Bogie JF, Stinissen P, Hendriks JJ Macrophage subsets and microglia in multiple sclerosis. Acta Neuropathol 2014; 128:191-213.
3. Hamilton JA. Colony-stimulating factors in inflammation and autoimmunity. Nat Rev Immunol 2008; 8:533-544.
4. van Nieuwenhuijze A., Koenders M, Roeleveld D., Sleeman MA, van den Berg W, Wicks IP. GM-CSF as a therapeutic target in inflammatory diseases. Mol Immunol 2013; 56:675-682.
5. Hartmann FJ, Khademi M, Aram J., et al. Multiple sclerosis-associated IL2RA polymorphism controls GM-CSF production in human TH cells. Nat Commun 2014; 5:5056.
6. Constantinescu CS, Farooqi N, O'Brien K, Gran B. Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS). Br J Pharmacol 2011; 164:1079-1106.
7. McQualter JL, Darwiche R, Ewing C., et al. Granulocyte macrophage colony-stimulating factor: a new putative therapeutic target in multiple sclerosis. J Exp Med 2001; 194:873-882.
8. Ponomarev ED, Shriver LP, Maresz K, Pedras-Vasconcelos J, Verthelyi D., Dittel BN. GM-CSF production by autoreactive T cells is required for the activation of microglial cells and the onset of experimental autoimmune encephalomyelitis. J Immunol 2007; 178:39-48.
9. King IL, Dickendesher TL, Segal BM Circulating Ly-6C1 myeloid precursors migrate to the CNS and play a pathogenic role during autoimmune demyelinating disease. Blood 2009; 113:3190-3197.
10. Codarri L, Gyülvészi G, Tosevski V, et al. RORgt drives production of the cytokine GM-CSF in helper T cells, which is essential for the effector phase of autoimmune neuroinflammation. Nat Immunol 2011; 12:560-567.
11. El-Behi M., Ciric B, Dai H., et al. The encephalitogenicity of T(H) 17 cells is dependent on IL-1- and IL-23-induced production of the cytokine GM-CSF. Nat Immunol 2011; 12:568-575.
12. Steidl S, Ratsch O, Brocks B., Dürr M, Thomassen-Wolf E. In vitro affinity maturation of human GM-CSF antibodies by targeted CDR-diversification. Mol Immunol 2008; 46:135-144.
13. Minagar M, Alexander S. Blood-brain barrier disruption in multiple sclerosis. Mult Scler 2003; 9:540-549.
14. Behrens F, Tak PP, Ostergaard M, et al MOR103, a human monoclonal antibody to granulocyte-macrophage colony-stimulating factor, in the treatment of patients with moderate rheumatoid arthritis: results of a phase Ib/IIa randomized, double-blind, placebo-controlled, dose-escalation trial. Ann Rheum Dis Epub 2014 Feb 17.
15. Hummel J, McKendrick S, Brindley C., French R. Exploratory assessment of dose proportionality: review of current approaches and proposal for a practical criterion. Pharm Stat 2009; 8:38-49.
16. Huizar I, Kavuru MS Alveolar proteinosis syndrome: pathogenesis, diagnosis, and management. Curr Opin Pulm Med 2009; 15:491-498.
17. Weisman MH, Moreland LW, Furst D.E., et al. Efficacy, pharmacokinetic, and safety assessment of adalimumab, a fully human anti-tumor necrosis factor-alpha monoclonal antibody, in adults with rheumatoid arthritis receiving concomitant methotrexate: a pilot study. Clin Ther 2003; 25:1700-1721.
18. Zhou H, Jang H, Fleischmann R.M., et al. Pharmacokinetics and safety of golimumab, a fully human anti-TNF-alpha monoclonal antibody, in subjects with rheumatoid arthritis. J Clin Pharmacol 2007; 47:383-396.