Safety & Tolerability of the IRay System in Subjects With Exudative Choroidal Neovascularization (CNV) Secondary to Age-Related Macular Degeneration (AMD)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and clinical feasibility of the IRay System for the treatment of wet age-related macular degeneration (AMD).

Detailed Description
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The primary objective is to evaluate the safety and clinical feasibility of stereotactic radiotherapy with the Oraya IRay system for the treatment of choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD), as measured by incidence and severity of ocular radiation related serious adverse events (SAE) and adverse events (AE) in subjects treated with an 11, 16 or 24 Gray (Gy) macular dose through the 60-month follow-up visit.

Official Title
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A Pilot Study to Evaluate the Safety and Tolerability of the IRay Stereotactic Radiosurgery System in Subjects With Exudative Choroidal Neovascularization (CNV) Secondary to Age-Related Macular Degeneration (AMD)

Conditions
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Age-Related Macular Degeneration, Wet Age-Related Macular Degeneration, Macular Degeneration, Eye Diseases, Retinal Diseases

Intervention / Treatment
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* Device: IRay


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must be age 50 or older Women must be post-menopausal ≥1 year or surgically sterilized Subjects must have choroidal neovascularization lesion size of ≤11 total disc areas (28.26mm), and a greatest linear dimension of ≤6 mm Subjects must have Early Treatment Diabetic Retinopathy Study (ETDRS) best corrected visual acuity of 69 to 24 letters (20/40 to 20/320 Snellen Equivalent) in the study eye Subretinal hemorrhage (if any) must not comprise more than 50% of total lesion size, and may not involve the subfoveal space Exclusion Criteria: Subjects with prior or concurrent therapies including submacular surgery, thermal laser photocoagulation (with or without photographic evidence), photodynamic therapy and transpupillary thermotherapy (TTT) Subjects with concomitant disease in the study eye, including uveitis, diabetic retinopathy,presence of RPE tears or rips, acute ocular or periocular infection Subjects with advanced glaucoma (>0.8 cup to disk ratio) or intraocular pressure ≥30 mmHg in the study eye Previous glaucoma filtering surgery in the study eye Refractive error in the study eye demonstrating more than -8 diopters of myopia (or globe axial length ≥26 mm). For subjects who have undergone prior refractive or cataract surgery in the study eye, the preoperative refractive error cannot exceed -8 diopters of myopia Subjects with any retinal vasculopathies, including diabetic retinopathy, retinal vein occlusions, etc. in the study eye

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 11 Gy IRay<br>Day 0 Lucentis followed by 11 Gy IRay, Lucentis at Month 1 and Lucentis PRN (N = 2) | Device: IRay<br>* Low voltage stereotactic radiotherapy system<br>|
| Experimental: 16 Gy IRay<br>Day 0 Lucentis followed by 16 Gy IRay, Lucentis at Month 1 and Lucentis PRN (N = 27) | Device: IRay<br>* Low voltage stereotactic radiotherapy system<br>|
| Experimental: 16 Gy IRay - Radiation First<br>16 Gy IRay and Lucentis PRN (N = 13) | Device: IRay<br>* Low voltage stereotactic radiotherapy system<br>|
| Experimental: 24 Gy IRay<br>Day 0 Lucentis followed by 24 Gy IRay, Lucentis at Month 1 and Lucentis PRN (N = 19) | Device: IRay<br>* Low voltage stereotactic radiotherapy system<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of ocular radiation-related adverse events |  | Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of ocular adverse events |  | Through month 60 | 
| Percentage of subjects who lose at least 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters in best corrected visual acuity (BCVA) |  | Month 12 | 
| Percentage of subjects gaining ≥ 15 ETDRS letters |  | Month 12 | 
| Percentage of subjects gaining ≥ 0 ETDRS letters |  | Month 12 | 
| Mean change in ETDRS visual acuity |  | Month 12 | 
| Mean time to anti-VEGF retreatment following 2nd mandatory injection (excluding radiation-first subjects) |  | Month 12 | 
| Mean total number of ranibizumab injections |  | Through month 12 and 24 | 
| Change in choroidal neovascularization (CNV) size by fluorescein angiography (FA) |  | Month 12 | 
| Change in total lesion size by fluorescein angiography (FA) |  | Month 12 | 
| Change in central retinal lesion thickness by optical coherence tomography (OCT) |  | Month 12 | 
| Change in central subfield thickness by optical coherence tomography (OCT) |  | Month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oraya, Oraya Therapeutics, Inc., low voltage stereotactic radiosurgery, radiosurgery, radiotherapy, IRay, AMD, Macular Degeneration, Wet AMD, xray, radiation, x ray, external beam radiation, Ranibizumab, Lucentis