A phase 1b/2a clinical trial evaluated the safety and tolerability of isunakinra, a novel topical interleukin-1 receptor inhibitor, for treatment of the signs and symptoms of dry eye disease (DED). The secondary objectives were to identify the DED population showing the best response to isunakinra, and to further describe the drug’s biological activity.
This double-masked, placebo-controlled trial enrolled 74 subjects with moderate to severe DED from 8 clinical sites across the United States. Subjects were randomized to isunakinra ophthalmic solution 5 mg/ml, 20 mg/ml, or vehicle 3-times daily in each eye for 6 weeks.
The primary measure of efficacy was change in the ocular surface disease index (OSDI) score at 6 weeks compared with baseline. Additional endpoints included corneal fluorescein staining (CFS) and individual symptom assessments, such as eye pain. After 6 weeks, similar clinically relevant improvements in OSDI scores (38%) and CFS (33%) were observed in the isunakinra dose groups compared with baseline. However, these changes were not statistically significant compared to the vehicle group.
The authors noted that significantly more subjects in the vehicle group used rescue artificial tears compared to those in the isunakinra group.
Both doses of isunakinra were safe and well tolerated when given for 6 weeks. The frequency of adverse events was similar between groups. Plasma isunakinra concentration values were all below the limit of quantitation, indicating no systemic exposure to isunakinra.
This was a proof-of-concept study that was not powered to show statistical significance. There was a strong vehicle response for both signs and symptoms. However, this is a commonly observed phenomenon in dry eye clinical studies.
Although too early to significantly impact clinical practice, this new anti-inflammatory drug candidate appears to be a safe and promising addition to dry eye therapeutics. It may be especially beneficial for managing DED-associated ocular pain through its mechanism of decreasing hyperalgesia through nociception. A phase 3 study with adequate power will further assess the safety and efficacy of isunakinra for ocular surface diseases.