title: Phase 1b randomized, double-blind study of namilumab, an anti-granulocyte macrophage colony-stimulating factor monoclonal antibody, in mild-to-moderate rheumatoid arthritis.
abstract: Namilumab (AMG203) is an immunoglobulin G1 monoclonal antibody that binds with high affinity to the GM-CSF ligand. This was a phase 1b, randomized, double-blind study (PRIORA) to assess namilumab in active, mild-to-moderate rheumatoid arthritis (RA). The primary outcome was the safety and tolerability of repeated subcutaneous injections of namilumab in patients with mild-to-moderate RA.
  
  
  
  Adults with mild-to-moderate RA on stable methotrexate doses for ≥12 weeks were eligible. Patients received three subcutaneous injections of namilumab 150 or 300 mg, or placebo on days 1, 15, and 29, with 12 weeks' follow-up. Primary objective was safety/tolerability.
  
  
  
  Patients in cohort 1 were randomized to namilumab 150 mg (n = 8) or placebo (n = 5). In cohort 2, patients were randomized to namilumab 300 mg (n = 7) or placebo (n = 4). Incidence of treatment-emergent adverse events (TEAEs) was similar across the three groups (namilumab 150 mg: 63%; namilumab 300 mg: 57%; placebo: 56%). TEAEs in ≥10% of patients were nasopharyngitis (17%) and exacerbation/worsening of RA (13%). No anti-namilumab antibodies were detected. The pharmacokinetics of namilumab were linear and typical of a monoclonal antibody with subcutaneous administration. In a post hoc efficacy, per protocol analysis (n = 21), patients randomized to namilumab showed greater improvement in Disease Activity Score 28 (erythrocyte sedimentation rate and C-reactive protein [CRP]), swelling joint counts and tender joint counts compared with placebo. Difference in mean DAS28-CRP changes from baseline between namilumab and placebo favored namilumab at both doses and at all time points. In addition area under the curve for DAS28-CRP was analyzed as time-adjusted mean change from baseline. A significant improvement in DAS28-CRP was shown with namilumab (150 and 300 mg groups combined) compared with placebo at day 43 (p = 0.0117) and also 8 weeks after last dosing at day 99 (p = 0.0154).
  
  
  
  Subcutaneous namilumab was generally well tolerated. Although namilumab demonstrated preliminary evidence of efficacy, patient numbers were small; phase 2 studies are ongoing.
  
  
  
  ClinicalTrials.gov, NCT01317797 . Registered 18 February 2011.
authors.affiliation: Leiden University Medical Center, Albinusdreef 2, PO Box 9600, 2300RC, Leiden, The Netherlands.
authors.forename: T W J
authors.initials: TW
authors.lastname: Huizinga
authors.affiliation: Medical University of Plovdiv, UMHAT Kaspela, Plovdiv, Bulgaria.
authors.forename: A
authors.initials: A
authors.lastname: Batalov
authors.affiliation: University Hospital (MHAT) St Ivan Rilski, Sofia, Bulgaria.
authors.forename: R
authors.initials: R
authors.lastname: Stoilov
authors.affiliation: Takeda Pharmaceuticals International, Deerfield, IL, USA.
authors.forename: E
authors.initials: E
authors.lastname: Lloyd
authors.affiliation: Takeda Pharmaceuticals International GmbH, Zurich, Switzerland.
authors.forename: T
authors.initials: T
authors.lastname: Wagner
authors.affiliation: Takeda Pharmaceuticals International, 61 Aldwych, London, WC2B 4AE, UK.
authors.forename: D
authors.initials: D
authors.lastname: Saurigny
authors.affiliation: Takeda Pharmaceuticals International, 61 Aldwych, London, WC2B 4AE, UK.
authors.forename: B
authors.initials: B
authors.lastname: Souberbielle
authors.affiliation: Takeda Pharmaceuticals International, 61 Aldwych, London, WC2B 4AE, UK. ehsanollah.esfandiari@takeda.com.
authors.forename: E
authors.initials: E
authors.lastname: Esfandiari
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors*; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C000624713:namilumab
keywords: GM-CSF; Namilumab; Phase 1b; Rheumatoid arthritis