The first-in-human ongoing clinical trial of OPT-302, a novel VEGF-C/D ‘Trap’ therapy for wet age-related macular degeneration has generated positive data from its Phase one study, according to a statement released to the Australian Stock Exchange by its developer, Opthea.
OPT-302 is being trialed as a monotherapy and in combination with Lucentis in patients with wet macular degeneration who are either treatment naive or have demonstrated a sub-optimal response to prior anti-VEGF therapy.
Speaking of the Phase one study results, Dr. Pravin Dugel, managing director of Retinal Consultants Arizona and a member of Opthea’s clinical advisory board said, “Combination therapy with OPT-302 and standard of care Lucentis is both feasible and well tolerated in patients who are either naive to treatment or resistant to prior therapy.
OPT-302 is being trialed as a monotherapy and in combination with Lucentis in patients with wet macular degeneration who are either treatment naive or have demonstrated a sub-optimal response to prior anti-VEGF therapy
“Although the preliminary clinical activity data to date is based on a small number of patients, the promising gains in vision and anatomic improvements on spectral domain-optical coherence tomography (SD-OCT) that have been observed suggest that combined inhibition of VEGF-C/D and VEGF-A may lead to improved outcomes over Lucentis alone.”
The study, being undertaken under an Investigational New Drug (IND) program with the US Food and Drug Administration at 14 sites across America, comprises two parts: a sequential dose escalation and a randomised dose expansion study.
Twenty patients (mean age 74.8 years) were enrolled in the Phase 1 dose escalation into three OPT-302 dose level groups (0.3, 1 or 2 mg) in combination with Lucentis (0.5 mg) and an OPT-32 monotherapy group (2 mg). Patients received three intravitreal injections of OPT-302 either alone or in combination with Lucentis at four week intervals, with a week 12 follow-up visit one month after the third dose.
Patients who received OPT-302 monotherapy were provided with a Lucentis rescue therapy at investigator discretion or if they had a 5 ≥ letter decrease in vision and no reduction in central subfield thickness (CST) of at least 10 per cent with presence of fluid. All cohorts enrolled two naive patients and three patients who had received prior anti-VEGF-A therapy, with the exception of cohort 2 (OPT-302 1.0 mg + Lucentis), which had enrolled five previously treated patients.
The Phase one dose escalation study met its primary objective with OPT-302 demonstrating safety and tolerability both as a monotherapy and in combination with standard of care Lucentis. Specifically, no dose limiting toxicities and no treatment-related serious adverse events were observed through week 12 of the study.
Secondary endpoints, which included changes from baseline in best corrected visual acuity and anatomic measures (central subfield thickness (CST)) on spectral domain-optical coherence tomography through week 12, demonstrated encouraging clinical activity of OPT-302 in both treatment naive patients and those who showed a sub-optimal response to prior anti-VEGF-A therapy.
Overall, a majority of patients (16/19 evaluable at week 12) maintained or gained vision by week 12, compared to baseline and the other three patients that all received combination OPT-302 plus Lucentis therapy did not lose more than three letters (range -2 to -3 letters). The mean gain in visual acuity overall from baseline at week 12 in treatment nave patients who received OPT-302 plus Lucentis was 16.5 letters (n=4) and 9.5 letters in the 2 mg OPT-302 plus Lucentis dose cohort (n=2). The mean visual acuity gain from baseline at 12 in patients who showed a sub-optimal response to prior anti-VEGF –A therapy was four letters with combination OPT-302 plus Lucentis (n-10 evaluable patients; mean number of prior treatment injections = 10.5, range 3 – 55).
The mean central subfield thickness (CST)decreased in all combination OPT-302 plus Lucentis treatment groups at week 12, with a mean reduction from baseline at 214µM (42.7 percent) in treatment naïve patents (n=4, mean baseline CST 501.7µM) and 42 µM (10.8 per cent) in patients who showed a sub-optimal response to prior anti-VEGF –A therapy (n-10 evaluable patients, mean baseline CST 394 µM).
In the OPT-302 monotherapy cohort, 3/5 patients (1 naive and two prior treated) did not require rescue with anti-VEGF-A therapy. At week 12, in patients that did not undergo rescue, there was a mean visual acuity gain of 3.3 letters from baseline (range two to six letters) and a mean increase in CST of 18 µM.
Opthea is actively accruing up to 30 additional patients for the Phase 2a dose expansion study cohorts.