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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
51
Opthea Investigative Site
Phoenix, Arizona, United States
Opthea Investigative Site
Beverly Hills, California, United States
Opthea Investigative Site
Sacramento, California, United States
Opthea Investigative Site
Santa Maria, California, United States
Opthea Investigative Site
Fort Myers, Florida, United States
Opthea Investigative Site
Pensacola, Florida, United States
Opthea Investigative Site
Winter Haven, Florida, United States
Opthea Investigative Site
Wichita, Kansas, United States
Opthea Investigative Site
Bloomfield, New Jersey, United States
Opthea Investigative Site
Charlotte, North Carolina, United States
...and 4 more locations
Safety (Adverse Events)
Subject incidences of ophthalmic and systemic Adverse Events during study and follow-up period
Time frame: Up to 1 month after the last dose
Mean change in Best Corrected Visual Acuity (BCVA) from baseline
Mean change in Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA from baseline
Time frame: 6 months
Mean change in central retinal thickness from baseline
Changes in intra- or sub-retinal fluid measured as mean change in central retinal thickness or macula volume by Spectral Domain Optical Coherence Tomography (SD-OCT)
Time frame: 6 months
Mean change in Choroidal Neovascularization (CNV) lesion area from baseline
Change in CNV size according to fluorescein angiogram
Time frame: 6 months
Mean number of retreatment injections of anti-VEGF-A therapy during long term follow-up (week 12 to 24)
Time frame: 3 months
Need for 'rescue therapy' with ranibizumab in subjects receiving OPT-302 monotherapy
Time frame: 3 months
Assess the Pharmacokinetic profile of OPT-302 alone and in combination with ranibizumab following intravitreal administration
Mean systemic OPT-302 Concentration-Time profile
Time frame: Up to 28 days post-dose
Anti-OPT-302 antibody formation
Incidence of anti-OPT-302 antibody formation
Time frame: Pre-dose and up to 3 months post-dose
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.