Apeliotus Technologies proposes to develop a new clinical trial endpoint for age-related macular degeneration (AMD) based on dark adaptation. A major challenge in attacking AMD is the lack of adequate clinical trial endpoints. Visual acuity is currently the only accepted functional endpoint; however it is minimally impacted until the late stages of the disease when substantial vision loss has already occurred. Consequently, early-stage AMD trials are economical infeasible, requiring five to seven years and/or thousands of patients to detect a meaningful visual acuity affect. Dark adaptation is a clinical hallmark of early AMD, and is therefore an ideal candidate to address this challenge. Our AdaptRx dark adaptometer uses a proprietary method for measuring dark adaptation speed (the rate of transition from being light adapted to being dark adapted) that has been shown to be a sensitive biomarker for AMD starting at its earliest stages. The goal of this project is to validate dark adaptation as a surrogate marker for future vision loss using the AdaptRx. The specific aims for this SBIR Phase I feasibility proposal are: (1) development of a sensitive, quantitative dark adaptation protocol suitable for clinical trial use, and (2) clinical confirmation that this protocol quantifies dark adaptation speed for early and intermediate AMD patients (the target treatment population). Pilot studies have identified several promising protocols. They will be evaluated with a cohort of benchmark AMD patients to select the best option, and the ability of the selected protocol to reproducibly discriminate early and intermediate AMD patients will then be tested in a small clinical study (N=32). If we are successful, a follow-on SBIR Phase II proposal will be submitted for a multi-year prospective study of AMD patients to validate that dark adaptation impairment predicts imminent visual acuity loss. Pennsylvania State College of Medicine, Harvard Medical School and the National Eye Institute are collaborating with Apeliotus Technologies on this project.
Public Health Relevance: Age-related macular degeneration (AMD) is the leading cause of adult blindness in developed countries. It affects over 30 million people worldwide, including one in six over age 65 and one in three over age 75. A clinical trial endpoint sensitive to early AMD would accelerate the development of early- stage interventions aimed at arresting or curing this disease before the devastation of late-stage vision loss and blindness.
Public Health Relevance Statement: PROJECT NARRATIVE Age-related macular degeneration (AMD) is the leading cause of adult blindness in developed countries. It affects over 30 million people worldwide, including one in six over age 65 and one in three over age 75. A clinical trial endpoint sensitive to early AMD would accelerate the development of early- stage interventions aimed at arresting or curing this disease before the devastation of late-stage vision loss and blindness.
Project Terms: 18-ethenyl-4,4a-dihydro-3,4-bis(methoxycarbonyl)-4a,8,14,19-tetramethyl-23H,25H-benzo(b)porphine-9,13-dipropanoic acid monomethyl ester; 21+ years old; Address; Adult; Affect; Age; Age related macular degeneration; Aged 65 and Over; Alabama; Appearance; Articulation; BPD verteporfin; BPD-MA; Benchmarking; Benzoporphyrin Derivative Monoacid Ring A; Best Practice Analysis; Biological; Blindness; Characteristics; Choroidal Neovascularization; Clinical; Clinical Evaluation; Clinical Research; Clinical Study; Clinical Testing; Clinical Trials; Clinical Trials, Phase III; Clinical Trials, Unspecified; Dark Adaptation; Developed Countries; Developed Nations; Developing Countries; Developing Nations; Development; Diagnostic; Disease; Disorder; Doctor of Philosophy; Drugs; Druse; Drusen; Early treatment; Elderly; Elderly, over 65; Epidemiology; Future; Goals; Grant; Human, Adult; Impairment; Industrialized Countries; Industrialized Nations; Intervention; Intervention Strategies; Joints; Lead; Less-Developed Countries; Less-Developed Nations; Letters; Light; Lucentis; Maculopathy, Age-Related; Measures; Medical; Medication; Medicine; Methods; Na element; National Eye Institute; Neovascularization, Choroid; Novartis Ophthalmics brand of verteporfin; Novartis brand of verteporfin; Ophthalmology; Outcome; Partial Sight; Patients; Pb element; Pennsylvania; Ph.D.; PhD; Pharmaceutic Preparations; Pharmaceutical Preparations; Phase; Phase 3 Clinical Trials; Phase III Clinical Trials; Photoradiation; Pilot Projects; Population; Principal Investigator; Prospective Studies; Protocol; Protocols documentation; Protocols, Treatment; QLT brand of verteporfin; RGM; Regimen; Research; Retinal Diseases; Retinal Disorder; Rights; Role; SBIR; SBIRS (R43/44); Science of Medicine; Scotopic Adaptation; Screening procedure; Severities; Sight; Site; Small Business Innovation Research; Small Business Innovation Research Grant; Sodium; Solid; Speed; Speed (motion); Staging; Surrogate Markers; Technology; Testing; Third-World Countries; Third-World Nations; Treatment Protocols; Treatment Regimen; Treatment Schedule; Under-Developed Countries; Under-Developed Nations; Universities; Verteporfin; Vision; Vision, Diminished; Vision, Low; Vision, Reduced; Vision, Subnormal; Visual Acuity; Visual impairment; Visudyne; Work; adult human (21+); advanced age; base; benzoporphyrin D; biomarker; clinical investigation; clinical test; cohort; college; commercialization; design; designing; disease/disorder; drug candidate; drug development; drug/agent; elders; experience; geographic atrophy; geriatric; heavy metal Pb; heavy metal lead; improved; interest; interventional strategy; late life; later life; medical schools; older adult; older person; phase 3 study; phase 3 trial; phase III trial; pilot study; pre-clinical; preclinical; professor; protocol, phase III; public health relevance; ranibizumab; research clinical testing; retina disease; retina disorder; retinopathy; rhuFab V2; screening; screenings; senile macular disease; senior citizen; social role; study, phase III; tool; validation studies; verteporphin; visually impaired
