Kiora: KIO-101 Eye Drop is Safe and Tolerable for Dry Eye Disease

Kiora: KIO-101 Eye Drop is Safe and Tolerable for Dry Eye Disease

December 15, 2021

Kiora Pharmaceuticals revealed topline data from its vehicle-controlled, randomized safety study of KIO-101 eye drops.

The study investigated 24 healthy people and 21 people who had ocular surface inflammation, which is a cause of dry eye disease.

The findings showed that KIO-101 was safe and tolerable, with statistically significant improvements in conjunctival hyperemia, a key inclusion criterion for the 21 patients with ocular surface inflammation who were enrolled in the study, and a recognized clinical sign in patients with ocular surface inflammation and dry eye.

These results warrant advancing KIO-101 into phase 2 studies of longer duration, according to a company news release.

KIO-201 is an eye drop and provides a thin coating to the surface of the eye, serving as a protectant to facilitate and accelerate corneal re-epithelization.

It is being developed for the management of corneal epithelial defects and for the re-epithelization of the ocular surface following surgery, under both traumatic and non-traumatic conditions.

“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

Principal Investigator Gerhard Garhöfer, MD, Associate Professor, Medical University of Vienna, led the randomized, double-masked, vehicle-controlled, single-site trial in Vienna, Austria.

The goal of the study was to see if KIO-101 was safe and tolerable 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).