NCT02543229

Study Evaluating the Safety, Pharmacokinetics and Pharmacodynamics of OPT-302 With or Without Lucentis™ in Patients With Wet AMD

A Phase 1 Dose Escalation Study Evaluating the Safety, Pharmacokinetics and Pharmacodynamics of OPT-302 in Combination With Ranibizumab in Subjects With Wet AMD

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 51 (actual)
• Sponsor: Opthea Limited · Industry
• Sex: All
• Age: 50 Years
• Healthy volunteers: Not accepted

Summary

The 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). This study will be conducted in two parts: Part 1 will comprise an open label, sequential dose escalation and Part 2 a randomized dose expansion. OPT-302 is a soluble form of 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. Angiogenesis and vascular leakage are key hallmarks of wet AMD. Approved therapies for wet AMD include Eylea™ and Lucentis™ which block the activity of VEGF-A, but not VEGF-C or VEGF-D which are alternate members of the same family of molecules. 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.

Conditions

• Eye Diseases
• Macular Degeneration
• Retinal Diseases
• Retinal Degeneration
• Neovascularization, Pathologic

Interventions

Type	Name	Description
DRUG	OPT-302	OPT-302 will be administered by intravitreal injection once every month for 3 months
DRUG	Lucentis™	Lucentis™ (0.5 mg) will be administered by intravitreal injection once every month for 3 months

Timeline

• Start date: 2015-07-01
• Primary completion: 2017-02-07
• Completion: 2017-09-01
• First posted: 2015-09-07
• Last updated: 2017-11-06

Locations

14 sites across 1 country: United States