Development of Novel Clinical Endpoints in Intermediate AMD

Age Related Macular Degeneration (AMD) Clinical Trial

— MACUSTAR  

Official title:

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03349801
• Other study ID #: ECR-AMD-2017-13
• Secondary ID: MACUSTAR
• Status: Active, not recruiting
• Start date: March 26, 2018
• Est. completion date: November 30, 2022

Study information

• Verified date: May 2022
• Source: University Hospital, Bonn
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 718
• Est. completion date: November 30, 2022
• Est. primary completion date: November 30, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 55 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Age Related Macular Degeneration (AMD)
• Macular Degeneration

Intervention

Other:
• No intervention
According to clinical practice.

Locations

Country	Name	City	State
Denmark	Righospitalet Copenhagen	Copenhagen
France	Centre Hospitalier Intercommunal de Creteil	Créteil
France	Centre d'Investigation Clinique Centre National d'Ophtalmologie des Quinze-Vingts	Paris
Germany	University Hospital Bonn	Bonn
Germany	University Hospital Cologne	Cologne
Germany	Department of Ophthalmology, University of Freiburg	Freiburg
Germany	University Eye Hospital Munich	Munich
Germany	St. Franziskus Hospital	Münster
Germany	Universtiy Hospital Tuebingen	Tübingen
Germany	University Eye Hospital Ulm	Ulm
Italy	Luigi Sacco Hospital	Milan
Italy	Ospedale San Raffaele	Milan
Italy	G.B.Bietti Eye Foundation	Rom
Netherlands	Radboud University Medical Centre	Leiden
Netherlands	Radboud University Medical Centre	Nijmegen
Portugal	Centre for Clinical Trials, AIBILI	Coimbra
Portugal	Centro Hospitalar de São João, E.P.E.	Porto
United Kingdom	Queen's University Belfast	Belfast
United Kingdom	Gloucestershire Hospitals NHS Foundation Trust	Gloucester
United Kingdom	Moorfields Eye Hospital	London

Sponsors (14)

Lead Sponsor

Collaborator

Frank G. Holz

Association for Innovation and Biomedical Research on Light and Image, Bayer, Carl Zeiss Meditec AG, City, University of London, European Clinical Research Infrastructure Network, Hoffmann-La Roche, Innovative Medicines Initiative, La Fondation Voir et Entendre, Moorfields Eye Hospital NHS Foundation Trust, Novartis Pharmaceuticals, Radboud University Medical Center, University College, London, University of Sheffield

Countries where clinical trial is conducted

Denmark,  France,  Germany,  Italy,  Netherlands,  Portugal,  United Kingdom, 

Outcome

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

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