Clearside Biomedical announced positive topline results from its pivotal phase 3 clinical trial of suprachoroidal CLS-TA in patients with macular edema associated with noninfectious uveitis.
Suprachoroidal CLS-TA is Clearside’s proprietary suspension of the corticosteroid triamcinolone acetonide formulated for administration to the back of the eye via the suprachoroidal space (SCS).
Clearside enrolled 160 patients in this randomized, controlled, masked phase 3 pivotal clinical (PEACHTREE) trial. Of the 160 patients enrolled, 96 patients were randomized to the treatment arm to receive two 4.0 mg doses of suprachoroidal CLS-TA 12 weeks apart, and 64 patients were randomized to undergo sham procedures at the same 12-week interval. Patients were evaluated every 4 weeks for a total of 24 weeks, and a total of 155 patients, or 97% of those enrolled, completed the full evaluation period of the trial.
In the PEACHTREE trial, 47% of patients who received suprachoroidal CLS-TA every 12 weeks gained at least 15 letters in best corrected visual acuity (BCVA), as measured using the Early Treatment of Diabetic Retinopathy Study (“ETDRS”) scale, from baseline at week 24, compared to 16% of patients who underwent a sham procedure. This improvement, which was the primary endpoint of the trial, was statistically significant (P < 0.001). Further, in terms of improvements in BCVA, the mean change from baseline was better in the treatment arm than the sham arm at each monthly evaluation. The mean improvement from baseline was maintained throughout the evaluation period, with 9.6 letters gained at week 4 and 13.7 letters at week 24 in the active arm, compared to 1.2 letters at week 4 and 2.9 letters at week 24 in the control arm, respectively.
For the other key secondary endpoint, administration of suprachoroidal CLS-TA resulted in a mean reduction from baseline of 157 microns in central subfield thickness at week 24 in the active arm compared to a 19 micron mean reduction in the sham arm, a result that was also statistically significant (P < 0.001).
Suprachoroidal CLS-TA was generally well tolerated, with no treatment-related serious adverse events reported in the trial. Through 24 weeks, corticosteroid-related elevated intraocular pressure adverse events were reported for approximately 11.5% of patients in the CLS-TA treatment group, compared to no patients in the sham group.
Detailed results from PEACHTREE will be presented at an upcoming medical conference.
“These positive topline data from PEACHTREE are very encouraging for this population with macular edema as a complication due to their uveitis,” Rahul N. Khurana, MD, an investigator for PEACHTREE, Partner at Northern California Retina Vitreous Associates, and Clinical Associate Professor in Ophthalmology at UCSF Medical Center, said in a company news release. “The PEACHTREE study was the first pivotal phase 3 clinical trial of a drug candidate for patients with uveitic macular edema in which a BCVA measure was the primary efficacy endpoint, potentially raising the bar for future trials in this population. Typically, uveitic macular edema may persist despite adequate control of uveitis itself, and it is challenging to treat and may persist despite multiple interventions. Also, while corticosteroids are the most common treatment for all complications of uveitis, including the associated macular edema, systematic controlled studies of this kind are rare. I believe that based on these positive results, and if marketing authorization is obtained from the FDA, suprachoroidal CLS-TA has the potential to become a new paradigm for the treatment of visual impairment associated with macular edema associated with noninfectious uveitis.”
“Having nearly 50% of the PEACHTREE trial patients treated with suprachoroidal CLS-TA gain 15 or more letters in vision is highly compelling. It represents a huge step forward in advancing suprachoroidal administration of CLS-TA towards becoming a powerful new approach in potentially treating blinding eye diseases,” said Daniel H. White, Clearside’s Chief Executive Officer and President. “We currently expect to submit a new drug application for suprachoroidal CLS-TA in patients with macular edema associated with uveitis to the FDA in the fourth quarter of 2018, and we are also evaluating a number of options for submissions to regulatory agencies in additional territories outside of the United States.”
Suprachoroidal CLS-TA, used either alone or together with an intravitreal anti-VEGF agent, is being studied as part of Clearside’s pipeline of treatments for unmet or underserved blinding eye diseases where the pathologies manifest in the retina and the choroid.