Kiora Reports KIO-101 is Safe and Tolerable for Dry Eye Disease
Kiora Pharmaceuticals announced topline data from its vehicle-controlled, randomized safety study of KIO-101 eyedrops. The study evaluated 24 healthy subjects and 21 patients diagnosed with ocular surface inflammation, a driver of dry eye disease. The results demonstrated favorable safety and tolerability of KIO-101 as well as statistically significant improvements in conjunctival hyperemia, a key inclusion criterion for the 21 patients enrolled with ocular surface inflammation and a recognized clinical sign in patients with ocular surface inflammation and associated dry eye. These results warrant advancing KIO-101 into phase 2 studies of longer duration, according to a company news release.
KIO-101 is a small molecule DHODH inhibitor representing a novel approach to addressing ocular inflammation and dry eye disease. Previous generations of DHODH inhibitors are currently approved to treat patients with the systemic autoimmune diseases, multiple sclerosis and rheumatoid arthritis.
“As an exploratory study, our predetermined analysis plan was limited to only formal comparisons between groups for pharmacokinetics, safety and tolerability. A post-hoc analysis on predefined secondary efficacy outcomes showed a meaningful reduction in conjunctival hyperemia, consistent with inhibition of both T-cell proliferation and proinflammatory cytokine release that we would expect from an immune modulating DHODH inhibitor,” Eric J Daniels, MD, Chief Development Officer of Kiora, said in a company news release. “These early signs of a drug-related effect on clinical outcomes are encouraging and support KIO-101’s continued development for patients with ocular surface inflammation associated with dry eye disease.”
The topline results and observations include the following:
KIO-101 had a favorable safety and tolerability profile with no systemic serious adverse events (SAE) or ocular SAEs in any subjects tested.
Pharmacokinetic analysis demonstrated no detectable levels of KIO-101 in the plasma in the majority of subjects, consistent with the design of Kiora’s ophthalmic formulation.
Treatment with KIO-101 resulted in a statistically significant and clinically meaningful reduction in conjunctival hyperemia, an FDA accepted pivotal study “sign endpoint” for dry eye disease.
Results showed at day 13, 100% of patients treated with KIO-101 (14/14) saw a reduction >1 from baseline, measured on the Efron scale (0-5), versus only 42.8% with vehicle control (3/7) (P < 0.006).
The mean reduction in conjunctival hyperemia score from baseline to day 13 demonstrated statistical significance in active vs. vehicle control (-1.055 vs. -0.604; P=0.0316).
This apparent drug effect on conjunctival hyperemia was lost when patients were assessed at the Day 20 post-treatment follow-up, 8 days after the last dose was administered.
There was a numerical trend favoring KIO-101 in ocular surface disease index (OSDI), but no statistically significant differences were observed in tear break up time (TBUT), corneal staining, conjunctival staining nor other exploratory endpoints. A larger sample size and dosing period longer than two weeks is necessary to effectively evaluate a statistical drug effect on these efficacy endpoints.
Additional data will be submitted for presentation at an upcoming scientific/medical conference.
Trial Design
The randomized, double-masked, vehicle-controlled, single site study was conducted in Vienna, Austria and led by Principal Investigator Gerhard Garhöfer, MD, Associate Professor, Medical University of Vienna. The trial was designed to evaluate the safety and tolerability of KIO-101 in patients with ocular surface inflammation. A total of 21 patients were treated BID for 12 days with 0.15% of KIO-101 (n=14) or vehicle (n=7). The key inclusion criteria were conjunctival hyperemia score >2 and an OSDI of > 22. Primary endpoints included safety and tolerability. Secondary and exploratory endpoints included pharmacokinetics of KIO-101 as well as OSDI, conjunctival hyperemia, TBUT, corneal staining (Fluorescein), and conjunctival staining (Lissamine Green), ocular discomfort, lid edema, lid erythema.
This followed the phase 1 dose-ascending portion of the study in healthy volunteers, in which a total of 24 subjects were randomized to receive KIO-101 (0.05%, 0.15%, and 0.30%) or vehicle. Key endpoints assessed were safety, tolerability and plasma pharmacokinetics of KIO-101 following 1 day (single dose) and 12 days (48 doses).