Rezolute has commenced dosing in the Phase Ib RZ402-102 trial of its experimental oral drug, RZ402, to treat patients with diabetic macular edema (DME).

A selective and potent plasma kallikrein inhibitor (PKI), RZ402 hinders downstream bradykinin generation and pro-inflammatory, pro-coagulant and fluid-leakage contact-activation cascade.

The single centre, randomised, double-blind, placebo-controlled, multiple ascending dose Phase Ib trial will enrol at least 40 healthy adult subjects.

The trial will have four sequential ascending dose-level arms with ten participants in each.

Subjects within each dose cohort will be categorised in an 8:2 ratio to be administered either an oral solution of RZ402 or a matching placebo.

They will be analysed for pharmacokinetics and safety in-clinic for two weeks, prior to concluding an outpatient follow-up visit on day 28.

On obtaining blinded reviews of data from the preceding cohorts, the company will advance doses in a staggered manner every three weeks.

Blood biomarkers of target engagement or the kallikrein activity will be assessed as a systemic surrogate for DME. This process will use a precedent from trials of kallikrein inhibitors in a systemic vascular leakage syndrome or hereditary angioedema.

The trial aims to determine the safety profile of repeated doses of the drug, which will include the maximum tolerated dose, and its pharmacokinetics when given as daily oral doses for two weeks.

The trial is anticipated to complete with results available in the first quarter of next year, Rezolute noted.

Rezolute senior vice-president and clinical development head Brian Roberts said: “The Phase Ib study will evaluate the safety of RZ402 in healthy volunteers and inform the dose range selection in the Phase II proof-of-concept study, planned for next year.

“There is a significant unmet need for new ways to treat DME, due to the high treatment burden of current standard of care involving anti-VEGF injections into the eye.”

In the Phase Ia single-ascending dose study reported earlier this year, RZ402 was found to be safe and well-tolerated at all evaluated dose levels, with no dose-limiting toxicities observed.