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

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).

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.

The study will include subjects with no AMD or normal aging changes and subjects with AMD classified in accordance with the international Beckman Classification.

A total of 750 subjects will be recruited:

• 300 subjects will participate in the Cross-sectional part:

  • 50 with normal aging changes, no AMD
  • 50 with early AMD,
  • 50 with late AMD
  • 150 with iAMD

• 650 subjects will participate in the longitudinal part:

  • 600 iAMD
  • 50 early AMD