Rezolute announces initiation of a phase 2 study of RZ402 in patients with diabetic macular edema

The initiation of this Phase 2 study is an important milestone in the company’s mission to address the unmet need in the current DME treatment paradigm.

Rezolute Inc. announced this week that the company has initiated a Phase 2 proof-of-concept study for RZ402, a plasma kallikrein inhibitor (PKI) being developed as an oral therapy for the treatment of diabetic macular edema (DME).

According to a news release, the current standard of care for DME is anti-vascular growth factor (anti-VEGF) injections into the eye, requiring repeated administration over recurring periods of time to preserve vision, with significant treatment burden and occasional serious side effects. The invasive route of administration, coupled with inadequate responsiveness in some patients, leads to overall undertreatment and suboptimal vision outcomes in DME patients.

Raj Agrawal, MD, vice president, and head of Ophthalmological Clinical Development at Rezolute, pointed out in the news release that the initiation of this Phase 2 study is an important milestone in the company’s mission to address the unmet need in the current DME treatment paradigm.

“By targeting an alternative pathway and route of administration to the current standard of care, we believe that orally-administered RZ402 has the potential to be a less burdensome and more beneficial treatment option for all patients suffering with DME, including the approximately 50% of patients that don’t adequately respond to anti-VEGFs,” Agrawal said in a statement.

Moreover, Brian Roberts, MD, chief medical officer at Rezolute, noted that the company believes that RZ402 represents the potential for a significant change in the treatment paradigm of DME.

“By targeting this microvascular diabetes complication with an oral-systemic PKI, analogous to the management of other diabetes complications, RZ402 has the potential to improve overall clinical outcomes by driving earlier treatment intervention and preventing disease progression and vision loss for patients with DME,” he said in the statement. “We look forward to building upon the positive data generated in our Phase 1b trial and remain excited by the broad clinical potential of RZ402 to more effectively treat diseases associated with excessive kallikrein-kinin activity.”

According to the company, the Phase 2 study is a multi-center, randomized, double-masked, placebo-controlled, parallel-arm study to evaluate the safety, efficacy, and pharmacokinetics of RZ402 administered as monotherapy over a 12-week treatment period in participants with DME who are naïve to or have received limited anti-VEGF injections.

The company also noted that the study population will include DME patients with mild to moderate non-proliferative diabetic retinopathy (NPDR), central subfield thickness (CST) of ≥320 µm (or corresponding values), and best-corrected visual acuity (BCVA) of ≤78 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (≤20/25 on Snellen chart). Patients who have previously received more than three anti-VEGF injections prior to the study will be excluded.

Eligible participants will be randomly assigned equally, to one of three RZ402 active treatment arms at doses of 50, 200, and 400 mg, or a placebo control arm, and will receive study drug once daily for 12 weeks, before completing a four-week follow-up. The study is expected to enroll approximately 100 patients overall, across approximately 25 investigational sites in the United States. The principal endpoints of the trial include the change in CST, as measured by spectral domain ocular coherence tomography (SD-OCT), the change in visual acuity by ETDRS scale, the repeat dose pharmacokinetics of RZ402 in patients with DME, and the safety and tolerability of RZ402.