Study of Photobiomodulation to Treat Dry Age-Related Macular Degeneration (LIGHTSITE II)

Study Overview
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Brief Summary
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This LIGHTSITE II study is a double-masked, sham-controlled, parallel design, prospective multi-site study for the use of PBM as a treatment for visual impairment in subjects with dry AMD.

Detailed Description
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This study is a double-masked, sham-controlled, parallel design, prospective multi-site study for the use of PBM as a treatment for visual impairment in subjects with dry AMD. The target enrollment is 96 subjects in up to 10 centers in Europe, randomized at a 1:2 ratio into 2 groups: Sham Treatment (S-1) and PBM Treatment (T-2). Once 96 subjects have been enrolled in the study, if there are less than 144 eyes that qualify for the study, additional subjects will be enrolled until 144 eyes have been included in the study. S-1 will receive 3 sham treatments per week over 3 to 5 weeks starting at Baseline and starting again at Months 4 and 8. T-2 will receive 3 PBM treatments per week over 3 to 5 weeks starting at Baseline and starting again at Months 4 and 8. Each treatment series will total 9 treatments. Neither the subject nor the study staff will know which treatment the subject has been assigned. Subjects will receive standard visual outcome measurements including Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA, CSV-1000E contrast sensitivity (CS) and the Radner Reading Test prior to and following each treatment series as well as eye exams, fundus photographs, Heidelberg OCT and FAF imaging and optional Optos Ultra Wide Field (UWF) imaging of the retina at selected time intervals. Subjects will also complete the Visual Function Questionnaire 25 (VFQ-25) at selected time intervals.

Official Title
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A Double-Masked, Randomized, Sham-Controlled, Parallel Group, Multi-Center Study to Assess the Safety and Efficacy of Photobiomodulation (PBM) in Subjects With Dry Age-Related Macular Degeneration (AMD) (LIGHTSITE II)

Conditions
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Dry Age-related Macular Degeneration

Intervention / Treatment
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* Device: Valeda PBM treatment
* Device: Valeda Sham treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female at least 50 years of age at Screening visit Subjects with ETDRS BCVA letter score of between 50* and 75* (Snellen equivalent of 20/100 to 20/32). *If the subject meets this criterion at the Screening Visit but is outside the letter score by up to two letters at Baseline, the subject may be entered in the study. Subjects with a diagnosis of dry AMD as defined by the presence of drusen (regular or reticular pseudodrusen) and/or geographic atrophy (GA) visible on two of the following: color fundus images, OCT and/or Heidelberg FAF Able to communicate well with the Investigator and able to understand and comply with the requirements of the study Subject is informed of the nature of this study and has provided written informed consent in accordance with institutional, local and national regulatory guidelines Exclusion Criteria: Current or history of neovascular maculopathy that includes any of the following: Choroidal neovascularization (CNV) defined as pathologic angiogenesis originating from the choroidal vasculature that extends through a defect in Bruch's membrane Serous and/or hemorrhagic detachment of the neurosensory retina or retinal pigment epithelial (RPE) Retinal hard exudates (a secondary phenomenon resulting from chronic intravascular leakage) Subretinal and sub-RPE fibrovascular proliferation Disciform scar (subretinal fibrosis) Presence of center involving GA within the central ETDRS 1 mm diameter at Screening Media opacities, including cataracts, which might interfere with visual acuity or imaging in the study eye(s). Subjects should not be entered if there is likelihood that they will require cataract surgery in the study eye in the next 24 months. Posterior capsule opacification, which might interfere with visual acuity or imaging in the study eye(s). Subjects should not be entered if there is likelihood that they will require surgery in the study eye in the next 24 months Invasive eye surgery (e.g. cataract, capsulotomy) on a qualifying eye within three 3 months prior to Screening Ocular disorder or disease that partially or completely obstructs the pupil (e.g. posterior synechia in uveitis) Visually significant disease in any ocular structure apart from dry AMD (e.g. diabetic macular edema, glaucoma (using >2 eye drop medications, uncontrolled IOP and/or central/paracentral visual field loss), glaucoma surgery, active uveitis, active vitreous disease, intraocular tumor, retinal vascular diseases) Has a serious medical illness that will prevent the subject from performing study activities (including cardiac, hepatic, renal, respiratory, endocrinologic, neurologic, or hematologic disease) or, in the judgement of the Investigator, is likely to require surgical intervention or hospitalization at any point during the study Presence of or history of malignancy within the past 5 years other than non-melanoma skin or squamous cell cancer or cervical carcinoma in-situ Is non-ambulatory Presence or history of known light sensitivity to yellow light, red light, or near infrared radiation (NIR), or if there is a history of light activated CNS disorders (e.g. epilepsy, migraine) Use of any photosensitizing agent (e.g. topicals, injectables) within 30 days of treatment without consulting subject's physician History of drug, alcohol or substance abuse within 3 months prior to Screening Has received an investigational drug or treatment with an investigational device within 3 months prior to Screening If on any anti-oxidant or vitamin Age-Related Eye Disease Study (AREDS) supplement for dry AMD, has not been stabilized for a minimum of 1 month prior to Screening. Subjects are considered to be stable if they are taking the AREDS supplements consistently as prescribed by their treating doctor. Has received Low Vision Rehab/Therapy within 30 days prior to Screening or intends to receive during the study In the opinion of the Investigator, is unlikely to comply with the study protocol

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 120 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: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Valeda Light Delivery System
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PBM Treatment<br>The Valeda™ Light Delivery System will deliver 590, 660 and 850 nm wavelengths together. | Device: Valeda PBM treatment<br>* The Valeda Light Delivery System delivers 590, 660 and 850 nm wavelengths of light to the study eye. The Valeda Light Delivery System will treat through the open eyelid with the 590 nm and 850 nm wavelengths together. The 660 nm wavelength will be treated through the closed eyelid.<br>|
| Sham Comparator: Sham Treatment<br>The Valeda™ Light Delivery System will deliver non-effective treatment of the 590 and 660 nm wavelengths together. | Device: Valeda Sham treatment<br>* The sham mode emits an approximate 100x reduction in the highest dose for the 660 nm wavelengths as compared to the treatment mode, producing a slightly duller light. The 850 nm (NIR) wavelength (which is not visible light) is not provided in the sham treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Corrected Visual Acuity | The primary efficacy endpoint will be the change in BCVA from Baseline to Month 9 as assessed using the ETDRS BCVA chart. | Month 9 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Corrected Visual Acuity | The first of the secondary analyses will test the difference between the sham-treated and PBM-treated subjects in mean change from baseline (pre-treatment) to Month 9 in BCVA. | Month 9 | 
| Contrast Sensitivity | The second of the secondary analyses will test the difference between the sham-treated and PBM-treated subjects in mean change from baseline (pre-treatment) to Month 9 in contrast sensitivity at 18 cycles/degree (CPD). | Month 9 | 
| Impact on Central Drusen Volume by OCT | The analyses will first examine change from the screening visit in central Drusen volume | Month 10 | 
| Impact on Central Drusen Thickness by OCT | The analyses will then examine change from the screening visit in central Drusen Thickness | Month 10 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dry AMD, Photobiomodulation, Visual Acuity, Contrast Sensitivity, Optical Coherence Tomography, Drusen