Opthea reported encouraging results from a Phase 1/2a clinical trial in wet AMD patients in April 2017.
The results indicated that OPT-302 is well tolerated when administered as a monotherapy and in combination with Lucentis® (ranibizumab) and suggested that combined therapy of OPT-302 with Lucentis® may lead to improved clinical outcomes over Lucentis® administered alone.
“The results seen in Opthea’s Phase 1/2A trial are very encouraging. The study has achieved both of its objectives by demonstrating a well-tolerated safety profile and clear signals of biological activity of OPT-302. The potential to treat patients with a combination therapy to provide additional clinical benefit over the current standard-of care, and do it with a complementary mechanism of action, would be a significant advance in the treatment of retinal neovascular disease and beneficial for our patients.”
Dr. Pravin Dugel, Managing Partner of Retinal Consultants of Arizona and clinical professor at the University of Southern California Eye Institute, Keck School of Medicine, member of Opthea’s Clinical Advisory Committee and Chief Investigator on the OPT-302-1001 study.
The Phase 1/2a clinical trial of OPT-302 in wet AMD patients was conducted under an FDA approved Investigational New Drug (IND) application at 14 clinical sites in the United States.
The trial was divided into two parts. Phase 1 was a first-in-human 20-patient dose-escalation study in which OPT-302 was administered at three escalating doses (0.3, 1.0 or 2.0 mg) in combination with Lucentis® and alone (as ‘monotherapy’) on a monthly basis for three months.
Phase 2a was a 31-patient dose-expansion study in which OPT-302 was administered at the top dose from the dose-escalation study (2.0 mg) in combination with Lucentis® and alone (as ‘monotherapy’) on a monthly basis for three months.
Further details on the Phase 1/2a trial can be found at www.clinicaltrials.gov, Clinical Trial Identifier: NCT02543229
The results of the 20-patient first-in-human Phase 1 dose-escalation study were reported in April 2016 and presented at the European Society of Retina Specialists (EURETINA) Congress on in Copenhagen, Denmark in September 2016.
The combined results of the 51-patient Phase 1/2a study were reported in April 2017 and subsequently published in a peer-reviewed ophthalmology journal (Dugel et. al., Ophthalmol. Retina, (2020), Volume 4 (Issue 3), 250-263: Phase 1 Study of OPT-302 Inhibition of Vascular Endothelial Growth Factors C and D for Neovascular Age-Related Macular Degeneration).
The primary outcome measurement of the study was assessment of safety and tolerability of OPT-302 administered via ocular (intravitreal) injection as a monotherapy and in combination with Lucentis®. 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 in the wet AMD lesions.
Of the 51 patients enrolled, 25 were newly diagnosed treatment-naïve patients, and 26 had received prior intravitreal anti-VEGF-A therapy. The majority of lesion types (72.5%) were occult, 23.5% were minimally classic and 4.0% were predominantly classic.
OPT-302 demonstrated a favourable safety profile in this study as a monotherapy and in combination with Lucentis® treatment.
In patients who received the combination OPT-302 (any dose) with Lucentis®, the mean change in best corrected visual acuity (BCVA) from baseline at 12 weeks was +10.8 letters in the treatment-naïve patients (n=18) and +4.9 letters in the prior-treated patients (n=19). The mean central subfield thickness (CST) also decreased in both patient groups, the mean change from baseline at 12 weeks for the treatment-naïve and prior-treated patients being -119 μM and -54 μM, respectively.
In patients receiving OPT-302 monotherapy (2.0 mg), 7/13 (54%) did not require anti-VEGF-A rescue therapy throughout the dosing period up to week 12, and the mean change in BCVA from baseline at 12 weeks was +5.6 letters.
