Abstract
Purpose :
To review the efforts involved with suprachoroidal injection of CLS-TA in development of a potential local treatment for noninfectious uveitis from preclinical studies through early clinical development including Phase 1/2 and Phase 2 trials
Methods :
Animal pharmacokinetic and pharmacodynamic data along with efficacy results from human phase 1/2 and phase 2 clinical trials will be presented. In each of these human trials, a single suprachoroidal injection of triamcinolone acetonide (TA) (4.0 mg/100 µL) was administered and a total of 22 subjects were followed for 6 months and 2 months respectively.
Results :
Animal data suggests a selective distribution of drug within ocular tissues following suprachoroidal injection, with higher amounts (by 1200%) accumulating in the choroid and retina. The vitreous and anterior segment were found to be relatively spared (ranging from below quantification levels in the anterior chamber to 4% in the vitreous) compared to drug distribution levels following intravitreal injection. Animal efficacy experiments have shown that a 10-fold lower amount of drug is effective when comparing suprachoroidal to intravitreal dosing. A human phase 2 randomized, masked trial (DOGWOOD; n=17) showed significant reduction in macular edema (164 µm; p=0.0017) and improvement in visual acuity (9.2 letters;p=0.0004) from baseline to the primary endpoint at 2 months in patients with macular edema due to noninfectious uveitis. Similar results were obtained in an open label phase 1/2 clinical trial. A mean gain in visual acuity of 11 letters at week 8 from baseline,while a mean reduction in edema of 182 µm was observed in the same time period in an analysis across both studies. No serious adverse events related to the drug were seen in either study and no increases in intraocular pressure (IOP) observed; no patient was administered IOP lowering medication. Available human safety data will be reviewed.
Conclusions :
Suprachoroidal injection of CLS-TA as a potential treatment of noninfectious uveitis appears to show promise for further development on account of the selective distribution of the drug, along with the potential for improved efficacy and safety relative to other periocular and intraocular administration routes. A phase 3 randomized, masked, controlled trial is currently underway as part of continued developmental efforts.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.