Opthea has reported positive outcomes from the Company’s Phase 2a clinical trial investigating OPT-302 administered in combination with the anti-VEGF-A therapy Eylea® (aflibercept) for the treatment of persistent/refractory central-involved diabetic macular edema (DME).
Opthea’s Phase 1b/2a DME clinical trial involves administration of OPT-302 in combination with Eylea to patients with central-involved DME despite having previously received standard of care anti-VEGF-A therapy.
The trial was a two-part study. Phase 1b was a 9-patient dose-escalation study in which OPT-302 was administered in combination with Eylea. The Phase 2a trial was a dose-expansion study which randomized patients in a 2:1 ratio to receive either OPT-302 (2 mg) administered in combination with Eylea, or Eylea monotherapy.
Further details on the Phase 1/2a trial can be found at www.clinicaltrials.gov, Clinical Trial Identifier: NCT03397264
The Phase 1b study was a 9-patient dose-escalation study in which OPT-302 was administered at three escalating doses (0.3, 1.0 and 2 mg) each in combination with Eylea® (aflibercept) (2 mg) on a monthly basis for 3 months.
The results of Phase 1b dose-escalation study were reported in October 2018.
The primary outcome measurement of the Phase 1b study was assessment of safety and tolerability of OPT-302 administered via ocular (intravitreal) injection in combination with Eylea® (aflibercept). The secondary outcome measurements of the trial included preliminary determinations of clinical activity, including evaluation of visual acuity using eye charts, and evaluation of anatomical changes at the back-of-the-eye.
OPT-302 administered in combination with Eylea® (aflibercept) demonstrated a favourable tolerability and safety profile.
The results also showed that eyes with persistent DME which were sub-responsive to multiple prior doses of anti-VEGF-A therapy demonstrated visual and anatomic improvement at 12 weeks following conversion to the OPT-302 combination therapy. A clear dose-response relationship of increased gains in best corrected visual acuity (BCVA) with ascending dose levels of OPT-302 combination treatment was observed, as well as a reduction in retinal swelling.
Opthea’s Phase 2a DME clinical trial was a randomized, double-masked, dose expansion trial that enrolled patients diagnosed with persistent center-involved DME despite regular administration of prior anti-VEGF-A monotherapy. These patients are considered to be a difficult-to-treat patient population since they have received prior anti-VEGF-A therapy and experienced a suboptimal clinical response.
The Phase 2a trial was conducted at 53 trial sites in the United States, Israel, Australia and Latvia. Of the 144 patients randomized in the trial, 115 patients conformed sufficiently with the trial protocol and were included in efficacy analyses.
The primary efficacy endpoint of the trial was the clinical response rate, defined as the proportion of patients receiving OPT-302 combination therapy that achieved a ≥5 letter gain in visual acuity at week 12 compared to baseline. Our predefined measure of success was a response rate of greater than or equal to 38% based on historical observations that show limited ability to achieve a ≥5 letter improvement in DME patients on long-term anti-VEGF-A monotherapy.
52.8% of patients treated with OPT-302 combination therapy achieved a ≥ letter improvement in visual acuity at week 12 compared to baseline, meeting the pre-specified primary efficacy endpoint for the trial.
The totality of secondary functional and anatomical responses observed in the patients enrolled in this trial indicate OPT-302 activity.
In addition, the greatest visual acuity gains were observed in patients with a prior-treatment history of aflibercept.
