Subconjunctival injection of XG-102, a JNK inhibitor peptide, in patients with intraocular inflammation: a safety and tolerability study.

Abstract

PURPOSE:

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: Talal Beydoun, Catherine Deloche, Julien Perino, Bridget-Anne Kirwan, Jean-Marc Combette, Francine Behar-Cohen
• Journal: Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics (J Ocul Pharmacol Ther) Vol. 31 Issue 2 Pg. 93-9 (Mar 2015) ISSN: 1557-7732 [Electronic] United States
• PMID: 25347151 (Publication Type: Clinical Trial, Phase I, Journal Article)

Chemical References

• Peptides
• MAP Kinase Kinase 4
• D-JNKI-1

Topics

• Adolescent
• Aged
• Dose-Response Relationship, Drug
• Eye Diseases (blood, drug therapy, enzymology)
• Female
• Humans
• Inflammation (blood, drug therapy, enzymology)
• Injections, Intraocular
• MAP Kinase Kinase 4 (antagonists & inhibitors, metabolism)
• MAP Kinase Signaling System (drug effects)
• Male
• Middle Aged
• Peptides (administration & dosage, adverse effects, blood)
• Postoperative Complications (drug therapy)