Date: 2016-04-21
Type of information: Results
phase: 1-2a
Announcement: results
Company: Opthea (Australia)
Product: OPT-302
Action
mechanism: protein. OPT-302 is a soluble form of vascular endothelial growth factor receptor 3 (VEGFR-3) comprising the extracellular domains 1-3 of human vascular endothelial growth factor receptor (VEGFR)-3 and the Fc fragment of human IgG1. It functions by binding and neutralizing the activity of vascular endothelial growth factor (VEGF)-C and VEGF-D on endogenous VEGFR-2 and VEGFR-3. VEGF-C and VEGF-D promote blood vessel development (angiogenesis) by binding and activating VEGFR-2 and VEGFR-3. VEGF-C is also a potent inducer of vascular permeability or leakage. Approved therapies for wet AMD include Eylea™ and Lucentis™ which block the activity of VEGF-A, but not VEGF-C or VEGF-D. VEGF-C and VEGF-D can stimulate blood vessel growth and leakage through the same pathway as VEGF-A (via VEGFR-2), as well as through pathways that are independent of VEGF-A (via VEGFR-3). Published studies have also indicated that VEGF-C and VEGF-D play an important role in mediating resistance to therapies that block VEGF-A such as Lucentis™ and Eylea™. Combination therapy with OPT-302 an anti-VEGF-A agent provides a more complete blockade of the VEGF family. This strategy targets functional redundancy in the VEGF pathway and mechanisms of 'resistance' or sub-response to VEGF-A inhibition. OPT-302 is currently being investigated in a Phase 1/2A clinical trial in wet AMD patients as a monotherapy and in combination with ranibizumab (Lucentis®).
Disease: wet age related macular degeneration (AMD)
Therapeutic area: Ophtalmological diseases
Country: USA
Trial
details: This purpose of this first-in-human study is to evaluate the safety, pharmacokinetics (PK) and pharmacodynamics of OPT-302 administered as monthly intravitreal injections for 3 months with and without Lucentis™ in patients with wet age related macular degeneration (AMD). The study is being conducted in two parts: Part 1 (Phase 1) comprises an open label, sequential dose escalation and will recruit at least 20 patients and Part 2 (Phase 2A) a randomized dose expansion that will recruit an additional ~30 patients and is aimed at further characterising the safety, pharmacokinetic profile and relationship between dose/PK and clinical activity of OPT-302 (+/- ranibizumab). ( NCT02543229)
Latest
news: * On April 21, 2016, Opthea, a developer of novel biologic therapies for the treatment of eye diseases, has successfully met the primary objective of safety in the dose escalation of its ongoing first-in-human clinical trial of OPT-302, a novel VEGF-C/D 'Trap' therapy for wet age-related macular degeneration (wet AMD). The dose escalation trial is investigating OPT-302 administered either alone or in combination with Lucentis® on a monthly basis for three months by ocular injection. The 28 day safety assessment period has now been completed for all 20 patients in the Phase 1 dose escalation trial. OPT-302 administered by intravitreal injection as a monotherapy (2.0 mg) or at three escalating doses (0.3, 1.0 or 2.0 mg) in combination with Lucentis® (0.5 mg) was safe and well tolerated at all dose levels in 20 patients with wet AMD who were either treatment naive or previously treated with standard of care. There were no dose limiting toxicities and a Maximum Tolerated Dose (MTD) was not reached with OPT-302. Adverse events were primarily related to the intravitreal injection procedure and were mild and manageable. There were no signs of infection inside the eye, or endophthalmitis, and no clinically significant changes in intraocular pressure, electrocardiograms, blood pressure or other vital signs during the safety assessment period at all dose levels of OPT-302.
With the 28 day safety assessment period complete for the patients in the Phase 1 dose escalation trial, patient recruitment for the randomised dose expansion Phase 2A study may now commence. The Phase 2A will enrol an additional ~30 subjects with wet AMD, randomised in a 1:1 ratio to two treatment groups of OPT-302 given as monotherapy or in combination with Lucentis® administered by intravitreal injection on a monthly basis for 3 months. Primary analysis data from the Phase 2A study is anticipated by the end of 2016.
