title: Multicenter Study of a Novel Topical Interleukin-1 Receptor Inhibitor, Isunakinra, in Subjects With Moderate to Severe Dry Eye Disease.
abstract: OBJECTIVE
  Isunakinra, formerly known as EBI-005, is a novel interleukin (IL)-1 receptor inhibitor developed for topical treatment of patients with dry eye disease (DED). This phase 1b/2a multicenter, double-masked, randomized, vehicle controlled environmental trial assessed the safety and biological activity of isunakinra in patients with moderate to severe DED.
  
  
  METHODS
  Subjects (N=74) were randomized to vehicle (placebo) or isunakinra (5 or 20 mg/mL) 3×/daily for 6 weeks. Evaluations included safety, tolerability, biological activity for signs (corneal fluorescein staining [CFS]), symptoms (pain or sore eyes and total Ocular Surface Disease Index [OSDI]), and reduction in rescue artificial tear use.
  
  
  RESULTS
  Topical administration of isunakinra (5 and 20 mg/mL) was safe and well tolerated and resulted in clinically relevant improvements in symptoms (OSDI score, painful/sore eye component of OSDI) and signs (total CFS) compared with baseline with no dose response. OSDI scores improved from baseline by 38% (18.9 points) at 6 weeks and CFS scores improved by 33% (3 points) in the isunakinra groups. These changes were not statistically significant compared with the vehicle. Use of artificial rescue tears was significantly reduced in the isunakinra treatment groups (mean=9 vials) compared with vehicle (mean=31 vials). The differences between isunakinra and vehicle treatments were more pronounced in subjects with OSDI scores less than 50 at baseline.
  
  
  CONCLUSIONS
  Isunakinra was safe, well tolerated and showed clinically meaningful improvements in signs and symptoms of DED. These results encouraged the design of an adequately powered study to characterize the safety and efficacy of isunakinra in ocular surface diseases.
authors.affiliation: Eleven Biotherapeutics (M.H.G., J.A., E.F.), Cambridge, MA; New England Eye Center (M.H.G.), Tufts Medical Center, Boston, MA; California Northstate College of Medicine (J.R.M.), Elk Grove, CA; Sall Research Medical Center, Inc. (K.S.), Artesia, CA; Wolstan and Goldberg Eye Associates (D.F.G.), Torrance, CA; Abrams Eye Center (M.A.), Cleveland, OH; Eye Clinics of South Texas (J.R.), San Antonio, CA; Virginia Eye Consultants (J.S.), Norfolk, VA; Tauber Eye Center (J.T.), Kansas City, MO; Comprehensive Eye Care Center (M.K.), Washington, MO; Durham Statistical Consulting (T.A.D.), Durham, NC.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Goldstein
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Martel
authors.forename: Kenneth
authors.initials: K
authors.lastname: Sall
authors.forename: Damien F
authors.initials: DF
authors.lastname: Goldberg
authors.forename: Marc
authors.initials: M
authors.lastname: Abrams
authors.forename: Jay
authors.initials: J
authors.lastname: Rubin
authors.forename: John
authors.initials: J
authors.lastname: Sheppard
authors.forename: Joseph
authors.initials: J
authors.lastname: Tauber
authors.forename: Michael
authors.initials: M
authors.lastname: Korenfeld
authors.forename: Jennifer
authors.initials: J
authors.lastname: Agahigian
authors.forename: Todd A
authors.initials: TA
authors.lastname: Durham
authors.forename: Eric
authors.initials: E
authors.lastname: Furfine
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004311:Double-Blind Method; D005260:Female; D015590:Fluorophotometry; D006801:Humans; D007638:Keratoconjunctivitis Sicca / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009883:Ophthalmic Solutions; D011446:Prospective Studies; D011506:Proteins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D013666:Tears / Q000502:physiology
chemical_list: C000604245:EBI-005; D009883:Ophthalmic Solutions; D011506:Proteins; D017472:Receptors, Interleukin-1