Development of Novel Clinical Endpoints in Intermediate AMD

Study Overview
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Brief Summary
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Development of novel clinical endpoints for interventional clinical trials with a regulatory and patient access intention in patients with intermediate age-related macular degeneration (AMD) - MACUSTAR

Detailed Description
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The purpose of the MACUSTAR clinical study is to develop novel clinical endpoints for clinical trials with a regulatory and patient access intention in patients with intermediate age-related macular degeneration (iAMD). Additional objectives are to characterize the visual impairment in iAMD and its progression, as well as identify risk factors for progression to late stage AMD. Moreover, MACUSTAR aims to optimize and standardize most relevant existing and/or rapidly available clinical endpoints in: visual functional outcomes measures structural outcomes measures patient reported outcomes measures (PROMs) The study will be composed by two parts: a cross-sectional part to technically evaluate the functional and structural outcome measures to support a biomarker qualification by regulatory authorities and payers; and a longitudinal part to assess the prognostic power of changes in retinal sensitivity (as measured by microperimetry) for progression from iAMD to late AMD (nAMD and GA).

Official Title
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Development of Novel Clinical Endpoints for Interventional Clinical Trials With a Regulatory and Patient Access Intention in Patients With Intermediate Age-related Macular Degeneration (AMD)

Conditions
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Age Related Macular Degeneration (AMD)

Intervention / Treatment
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* Other: No intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: General Inclusion criteria (applicable to all groups) Male and female subjects. Aged 55 - 85 years at baseline. Able and willing to provide written informed consent and to comply with the study protocol visits and assessments. Intermediate AMD Study eye must have iAMD and, The fellow eye must have iAMD and/or, in addition, extrafoveal GA (no atrophy within the central ETDRS subfield), maximum total GA size is 1.25 mm2. ETDRS letter chart BCVA in the study eye not worse than 72 letters (approximately 20/40 Snellen VA equivalent). All general inclusion criteria. Late AMD Subjects with bilateral GA, bilateral nAMD or nAMD in one eye and GA in the other. BCVA between 20/80 and 20/200 in study eye. All general inclusion criteria. Early AMD Subjects with medium drusen > 63μm and ≤ 125μm and no AMD pigmentary abnormalities in both eyes and not signs of intermediate or late AMD. All general inclusion criteria. No AMD No signs of early, intermediate or late AMD in both eyes. All general inclusion criteria only. Exclusion Criteria: General Exclusion criteria (applicable to all groups) Media opacity or eye movement disorder (nystagmus) that interferes with retinal imaging data quality in the opinion of the investigator. Severe ptosis, extraocular motility restriction or head tremor preventing adequate fundus visualization in the opinion of the investigator. Any signs of nAMD or GA (does not apply to the late AMD group). Any concurrent intraocular condition in the study eye (e. g. glaucoma or cataract) that, in the opinion of the investigator would either require surgical intervention during the study to prevent or treat visual loss that might result from that condition or affect interpretation of study results. Severe non-proliferative diabetic retinopathy, or proliferative diabetic retinopathy. Any diabetic macular edema or macular disease Ocular disorders in the study eye (i. e., pre-retinal membrane) at the time of enrolment that may confound interpretation of study results and compromise visual acuity. Diagnosis of uncontrolled glaucoma with intraocular pressure of >30 mmHg (despite current pharmacological or non-pharmacological treatment). Known systemic illness which in the opinion of the investigator will prevent from actively participating in the study. Concomitant treatment for AMD in either eye (concomitant use of vitamins/supplements is not excluded; does not apply to the late AMD group). Any periocular or intravitreal injections (IVT) in either eye (does not apply to the late AMD group). Participation in any other interventional trial. Obvious retinal changes due to causes other than AMD (e.g. evidenced by an existing diagnosis of monogenetic macular dystrophies, Stargardt disease, cone rod dystrophy, or toxic maculopathies). Any history of allergies to fluorescein. Intermediate AMD Any GA in the study eye Any extrafoveal GA larger than 1.25 mm2 in the fellow eye. All general exclusion criteria. Late AMD 1. All general exclusion criteria only. Early AMD Intermediate or late AMD (following Beckman classification) in any eye. All general exclusion criteria. No AMD Early to late AMD (following Beckman classification) in any eye. All general exclusion criteria.

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| no AMD<br>No interventions | Other: No intervention<br>* According to clinical practice.<br>|
| early AMD<br>No interventions. | Other: No intervention<br>* According to clinical practice.<br>|
| intermediate AMD<br>No interventions. | Other: No intervention<br>* According to clinical practice.<br>|
| late AMD<br>No interventions. | Other: No intervention<br>* According to clinical practice.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change from baseline in best corrected visual acuity (BCVA) using an early treatment diabetic retinopathy study (ETDRS) chart | standard parameter, tested for comparison (reference variable) | 3 years from baseline | 
| Mean change from baseline in scotopic and mesopic microperimetry sensitivity |  | 3 years from baseline | 
| Mean change from baseline in low luminance visual acuity (LLVA) |  | 3 years from baseline | 
| Mean change from baseline in vanishing optotypes visual acuity (VA) |  | 3 years from baseline | 
| Mean change from baseline in low luminance deficit (LLD) | LLD = BCVA-LLVA | 3 years from baseline | 
| Mean change from baseline in absolute rod threshold of the dark adaptation test |  | 3 years from baseline | 
| Mean change from baseline in rod intercept time of the dark adaptation test |  | 3 years from baseline | 
| Proportion of subjects with progression in dark adaptation deficit beyond coefficient of repeatability structural |  | 3 years from baseline | 
| Mean change from baseline in the cube root of drusen volume by spectral-domain optical coherence tomography (SD-OCT) |  | 3 years from baseline | 
| Mean change from baseline in retinal thickness by spectral-domain optical coherence tomography (SD-OCT) |  | 3 years from baseline | 
| Focal pigmentary changes captured by colour fundus photography (CFP) |  | 3 years from baseline | 
| Presence of refractile deposits |  | 3 years from baseline | 
| Presence of intraretinal cystoid spaces |  | 3 years from baseline | 
| Presence of localized retinal pigment epithelium (RPE) hypertransmission |  | 3 years from baseline | 
| Presence of localized disruption of ellipsoid zone |  | 3 years from baseline | 
| Presence of localized subsidence of the outer plexiform layer and the inner nuclear layer |  | 3 years from baseline | 
| Presence of hyporeflective wedge-shaped bands |  | 3 years from baseline | 
| Presence of reticular drusen/subretinal drusenoid deposits and associated local changes as determined by multimodal imaging |  | 3 years from baseline | 
| Changes in localized fundus autofluorescence signal alterations |  | 3 years from baseline | 
| Proportion of subjects with reduction in drusen volume |  | 3 years from baseline | 
| Proportion of subjects with study eye that progressed to geogrphic atrophy (GA) and/or neovascular age-related macular degeneration (nAMD) |  | 3 years from baseline | 
| Proportion of subjects with conversions to late AMD detected with fluorescein angiography (FA) that could be detected with OCT-A (at equipped sites) |  | 3 years from baseline | 
| Presence of quiescent choroidal neovascularisation (CNV) as assessed by optical coherence tomography angiography (OCT-A) (at equipped sites) |  | 3 years from baseline | 
| OCT-A findings (at equipped sites) |  | 3 years from baseline | 
| Mean change from baseline in patient-reported low luminance visual functioning, as measured by the vision impairment in low luminance (VILL) questionnaire, including the domains of reading & accessing information |  | 3 years from baseline | 
| Mean change from baseline in patient-reported low luminance visual functioning, as measured by the VILL questionnaire, including the domains of Orientation & mobility (incl. driving) |  | 3 years from baseline | 
| Mean change from baseline in patient-reported low luminance visual functioning, as measured by the VILL questionnaire, including the domains of safety |  | 3 years from baseline | 
| Mean change from baseline in patient-reported low luminance visual functioning, as measured by the VILL questionnaire, including the domains of socio-emotional well-being |  | 3 years from baseline | 
| Change in utility index from baseline as measure by the patient-reported outcome measure (PROM) utility index |  | 3 years from baseline | 
| Mean change from baseline in patient-reported health status and utility using the EQ-5D-5L questionnaire (EuroQol Group) |  | 3 years from baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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clinical endpoint, iAMD, biomarker