Evaluation of OLX10212 in Patients With Neovascular Age-related Macular Degeneration

This is a Phase 1, multicenter, open-label, single- and multi-dose, dose-escalating study of OLX10212 in patients with neovascular age-related macular degeneration (AMD). This study is composed of 2 parts: Part A and Part B. Part A is a single ascending dose study, and Part B is a multiple ascending dose study. The primary objective is to evaluate the safety and tolerability of single and multiple intravitreal injection(s) of OLX10212 in patients with neovascular AMD. The exploratory objectives are to evaluate the preliminary efficacy of single and multiple intravitreal injection(s) of OLX10212 in patients with neovascular AMD, and to evaluate the pharmacokinetics (PK) of single and multiple intravitreal injection(s) of OLX10212 in patients with neovascular AMD.

Inclusion Criteria:Men and women ≥50 years of agePrimary subfoveal CNV lesions secondary to AMD, including juxtafoveal lesions that affect the fovea, as evidenced by FA in the study eyeCNV must be ≥50% of the total lesion size in the study eyeETDRS BCVA score ranging from 20/60 to 20/400 in the study eyeClear ocular media and adequate pupillary dilation (able to dilate pupil to ≥4 mm using standard mydriatics) in the study eye to permit good stereoscopic fundus photographyRetinal thickness ≥250 μm in the macular region of the study eye as measured by SD-OCT with the presence of intraretinal or subretinal fluidWilling, committed, and able to return for all clinic visits and complete all study-related proceduresAble to read (or if unable to read due to visual impairment, be read to verbatim by the person administering the informed consent or by a family member), understand, and willing to sign the informed consent formExclusion Criteria:Any prior systemic treatment for neovascular AMD in either eye, except dietary supplements or vitamins or systemic anti-VEGF therapy, or planned use at any time during the studyAny prior treatment in the study eye with another investigational agent to treat neovascular AMD within 6 months prior to Day 0 or planned use at any time during the studyPrior treatment with anti-VEGF agents as follows:Anti-VEGF therapy in the study eye within 4 weeks prior to Day 0Anti-VEGF therapy in the study eye at any time to which there was no response, as defined by the presence of at least 1 of the following conditions: (1) persistent (plasma) fluid exudation, (2) unresolved or new hemorrhage, and (3) progressive lesion fibrosisAnti-VEGF therapy in the fellow eye with an investigational agent (not FDA approved, unless it is bevacizumab) within 3 months prior to Day 0 (prior treatment with an FDA approved anti-VEGF therapy in the fellow eye is allowed at any time)Systemic anti-VEGF therapy, investigational or FDA approved, within 3 months prior to Day 0 or planned use at any time during the studySubretinal hemorrhage in the study eye that is either >50% of the total lesion size or, if the blood is under the fovea, ≥1 disc area in sizeScar or fibrosis in the study eye involving >50% of the total lesion sizeRetinal pigment epithelial tears or rips in the study eye involving the maculaHistory of any vitreous hemorrhage in the study eye within 4 weeks prior to Day 0Presence of other causes of CNV in the study eye, including pathologic myopia, ocular histoplasmosis syndrome, angioid streaks, choroidal rupture, or multifocal choroiditisHistory or clinical evidence of diabetic retinopathy, diabetic macular edema, or any other vascular disease affecting the retina (other than AMD) in either eyeHistory of stage ≥2 macular hole in the study eyeAny prior intraocular or periocular surgery on the study eye within 3 months prior to Day 0 (lid surgery is allowed if it took place at least 1 month prior to Day 0 and is unlikely to interfere with OLX10212 injection). Prior vitrectomy in the study eye, surgery for retinal detachment in the study eye, and prior trabeculectomy or other filtration surgery in the study eye are not permitted at any timeUncontrolled glaucoma (defined as IOP ≥25 mmHg despite treatment with antiglaucoma medication) in the study eyeGlaucoma in the study eye requiring treatment with 3 or more antiglaucoma medicationsActive intraocular inflammation or history of uveitis in either eyePresence or history of ocular or periocular infection in either eye within 2 weeks prior to Day 0Presence or history of scleromalacia in either eyeAphakia or absence of posterior capsule in the study eye (unless due to yttrium aluminum garnet [YAG] posterior capsulotomy)Prior therapeutic radiation in the region of the study eye or planned use at any time during the studyPrior corneal transplant in the study eyeSignificant media opacities, including cataract, in the study eye that, in the opinion of the Investigator, could interfere with visual acuity, assessment of safety, or fundus photographyAny concurrent intraocular condition in the study eye (eg, cataract) that, in the opinion of the Investigator, could (1) require either medical or surgical intervention during the 24- or 32-week study period (Part A or Part B, respectively), (2) increase the risk to the patient beyond what is to be expected from standard intraocular injection procedures, or (3) otherwise interfere with the injection procedure or efficacy or safety evaluationHistory of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that might affect interpretation of the results of the study or renders the patient at high risk for treatment complicationsParticipation as a patient in any clinical study or prior systemic or ocular treatment with an investigational agent within 12 weeks prior to Day 0Prior systemic or intraocular treatment with long-acting steroids within 6 months prior to Day 0 or planned use at any time during the studyHistory of allergy to povidone iodineKnown allergy to fluorescein sodium for injection in angiographyUnwillingness among females who are pregnant, breastfeeding, or of childbearing potential to practice adequate contraception throughout the study. Adequate contraceptive measures include oral contraceptives (stable use for ≥2 cycles prior to Day 0), intrauterine device, Depo-Provera® (Pfizer, Inc., New York) or Norplant System® (Pfizer, Inc., New York) implants, bilateral tubal ligation, vasectomy, and condom or diaphragm plus contraceptive sponge, foam, or jelly. A female is considered to be of childbearing potential unless she is premenstrual, 1 year postmenopausal, or 3 months post-surgical sterilization. All females of childbearing potential, including those with post-tubal ligation, must have a negative urine pregnancy test result at Day 0 and every 4 weeks as outlined in the Schedule of Activities. A negative serum pregnancy test must be obtained at Screening.