Development of Novel Clinical Endpoints in Intermediate AMD

Overview

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

Full Title of Study: “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)”

Study Type

  • Study Type: Observational
  • Study Design
    • Time Perspective: Prospective
  • Study Primary Completion Date: February 28, 2022

Detailed Description

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).

Interventions

  • Other: No intervention
    • According to clinical practice.

Arms, Groups and Cohorts

  • no AMD
    • No interventions
  • early AMD
    • No interventions.
  • intermediate AMD
    • No interventions.
  • late AMD
    • No interventions.

Clinical Trial Outcome Measures

Primary Measures

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

Participating in This Clinical Trial

Inclusion Criteria

General Inclusion criteria (applicable to all groups)

1. Male and female subjects.

2. Aged 55 – 85 years at baseline.

3. Able and willing to provide written informed consent and to comply with the study protocol visits and assessments.

Intermediate AMD

1. Study eye must have iAMD and,

2. 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.

3. ETDRS letter chart BCVA in the study eye not worse than 72 letters (approximately 20/40 Snellen VA equivalent).

4. All general inclusion criteria.

Late AMD

1. Subjects with bilateral GA, bilateral nAMD or nAMD in one eye and GA in the other.

2. BCVA between 20/80 and 20/200 in study eye.

3. All general inclusion criteria.

Early AMD

1. Subjects with medium drusen > 63μm and ≤ 125μm and no AMD pigmentary abnormalities in both eyes and not signs of intermediate or late AMD.

2. All general inclusion criteria.

No AMD

1. No signs of early, intermediate or late AMD in both eyes.

2. All general inclusion criteria only.

Exclusion Criteria

General Exclusion criteria (applicable to all groups)

1. Media opacity or eye movement disorder (nystagmus) that interferes with retinal imaging data quality in the opinion of the investigator.

2. Severe ptosis, extraocular motility restriction or head tremor preventing adequate fundus visualization in the opinion of the investigator.

3. Any signs of nAMD or GA (does not apply to the late AMD group).

4. 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.

5. Severe non-proliferative diabetic retinopathy, or proliferative diabetic retinopathy.

6. Any diabetic macular edema or macular disease

7. 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.

8. Diagnosis of uncontrolled glaucoma with intraocular pressure of >30 mmHg (despite current pharmacological or non-pharmacological treatment).

9. Known systemic illness which in the opinion of the investigator will prevent from actively participating in the study.

10. Concomitant treatment for AMD in either eye (concomitant use of vitamins/supplements is not excluded; does not apply to the late AMD group).

11. Any periocular or intravitreal injections (IVT) in either eye (does not apply to the late AMD group).

12. Participation in any other interventional trial.

13. 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).

14. Any history of allergies to fluorescein.

Intermediate AMD

1. Any GA in the study eye

2. Any extrafoveal GA larger than 1.25 mm2 in the fellow eye.

3. All general exclusion criteria.

Late AMD

1. All general exclusion criteria only.

Early AMD

1. Intermediate or late AMD (following Beckman classification) in any eye.

2. All general exclusion criteria.

No AMD

1. Early to late AMD (following Beckman classification) in any eye.

2. All general exclusion criteria.

Gender Eligibility: All

Minimum Age: 55 Years

Maximum Age: 85 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Frank G. Holz
  • Collaborator
    • Bayer
  • Provider of Information About this Clinical Study
    • Sponsor-Investigator: Frank G. Holz, Prof. Dr. med. – University Hospital, Bonn
  • Overall Official(s)
    • Frank Holz, Prof. Dr. med., Principal Investigator, University Hospital, Bonn
  • Overall Contact(s)
    • Anna Lüning, +4922828715624, Anna.Luening@ukbonn.de

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