title: Subconjunctival injection of XG-102, a JNK inhibitor peptide, in patients with intraocular inflammation: a safety and tolerability study.
abstract: OBJECTIVE
  We aimed to investigate the safety, tolerability, and systemic diffusion of a single escalating dose of XG-102 (a 31-D-amino-acid peptide inhibiting JNK pathway activation), administered subconjunctivally in the treatment of post-surgery or post-trauma intraocular inflammation.
  
  
  METHODS
  This is a dose-escalating, tolerance Phase Ib study. Twenty patients with post-surgery or post-traumatic intraocular inflammation were assigned to 1 of the 4 dose escalating (45, 90, 450, or 900 μg XG-102) groups of 5 patients each. Patients were evaluated at 24, 48 h, 8, and 28 days following the administration of XG-102, including laboratory tests, standard eye examinations, vital signs, and occurrence of adverse events. A single plasma quantification of XG-102 was performed 30 min after administration, according to previous pharmacokinetics studies performed on volunteers.
  
  
  RESULTS
  A total of 17 non-serious adverse events, considered unrelated to the study treatment, were reported for 10 patients. The adverse event incidence was not related to the drug dose. All patients experienced a decrease in intraocular inflammation as of 24 h post-administration and this decrease was sustained up to 28 days thereafter. No patient required local injection or systemic administration of corticoids following the administration of XG-102. XG-102 was undetectable in the first 3 dose groups. In the fourth-dose group (900 μg) the XG-102 plasma levels were above the limit of detection for 3 patients and above the limit of quantification for 1 patient.
  
  
  CONCLUSIONS
  In this first clinical trial using XG-102, administered as a single subconjunctival injection as adjunct therapy, in patients with recent post-surgery or post-trauma intraocular inflammation is safe and well tolerated. Further studies are required to evaluate its efficacy.
authors.affiliation: 1 Department of Ophthalmology, AP-HP Hôtel-Dieu, Paris, France .
authors.forename: Talal
authors.initials: T
authors.lastname: Beydoun
authors.forename: Catherine
authors.initials: C
authors.lastname: Deloche
authors.forename: Julien
authors.initials: J
authors.lastname: Perino
authors.forename: Bridget-Anne
authors.initials: BA
authors.lastname: Kirwan
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Combette
authors.forename: Francine
authors.initials: F
authors.lastname: Behar-Cohen
mesh_terms: D000293:Adolescent; D000368:Aged; D004305:Dose-Response Relationship, Drug; D005128:Eye Diseases / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology; D056965:Injections, Intraocular; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage* / Q000009:adverse effects* / Q000097:blood; D011183:Postoperative Complications / Q000188:drug therapy
chemical_list: D010455:Peptides; D048670:MAP Kinase Kinase 4; C478085:D-JNKI-1