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Development of Novel Clinical Endpoints in Intermediate AMD (MACUSTAR)

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ClinicalTrials.gov Identifier: NCT03349801
Recruitment Status : Recruiting
First Posted : November 22, 2017
Last Update Posted : December 31, 2018
Sponsor:
Collaborators:
Bayer
Moorfields Eye Hospital NHS Foundation Trust
Novartis Pharmaceuticals
Association for Innovation and Biomedical Research on Light and Image
City, University of London
European Clinical Research Infrastructure Network
La Fondation Voir et Entendre
Hoffmann-La Roche
Radboud University
University of Sheffield
University College, London
Carl Zeiss Meditec AG
Innovative Medicines Initiative
Information provided by (Responsible Party):
Frank G. Holz, University Hospital, Bonn

Brief 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

Condition or disease Intervention/treatment
Age Related Macular Degeneration (AMD) Other: No intervention

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).

Study Type : Observational
Estimated Enrollment : 750 participants
Observational Model: Cohort
Time Perspective: Prospective
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)
Actual Study Start Date : March 26, 2018
Estimated Primary Completion Date : February 28, 2022
Estimated Study Completion Date : February 28, 2022

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
no AMD
No interventions
Other: No intervention
According to clinical practice.

early AMD
No interventions.
Other: No intervention
According to clinical practice.

intermediate AMD
No interventions.
Other: No intervention
According to clinical practice.

late AMD
No interventions.
Other: No intervention
According to clinical practice.




Primary Outcome Measures :
  1. 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)

  2. Mean change from baseline in scotopic and mesopic microperimetry sensitivity [ Time Frame: 3 years from baseline ]
  3. Mean change from baseline in low luminance visual acuity (LLVA) [ Time Frame: 3 years from baseline ]
  4. Mean change from baseline in vanishing optotypes visual acuity (VA) [ Time Frame: 3 years from baseline ]
  5. Mean change from baseline in low luminance deficit (LLD) [ Time Frame: 3 years from baseline ]
    LLD = BCVA-LLVA

  6. Mean change from baseline in absolute rod threshold of the dark adaptation test [ Time Frame: 3 years from baseline ]
  7. Mean change from baseline in rod intercept time of the dark adaptation test [ Time Frame: 3 years from baseline ]
  8. Proportion of subjects with progression in dark adaptation deficit beyond coefficient of repeatability structural [ Time Frame: 3 years from baseline ]
  9. 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 ]
  10. Mean change from baseline in retinal thickness by spectral-domain optical coherence tomography (SD-OCT) [ Time Frame: 3 years from baseline ]
  11. Focal pigmentary changes captured by colour fundus photography (CFP) [ Time Frame: 3 years from baseline ]
  12. Presence of refractile deposits [ Time Frame: 3 years from baseline ]
  13. Presence of intraretinal cystoid spaces [ Time Frame: 3 years from baseline ]
  14. Presence of localized retinal pigment epithelium (RPE) hypertransmission [ Time Frame: 3 years from baseline ]
  15. Presence of localized disruption of ellipsoid zone [ Time Frame: 3 years from baseline ]
  16. Presence of localized subsidence of the outer plexiform layer and the inner nuclear layer [ Time Frame: 3 years from baseline ]
  17. Presence of hyporeflective wedge-shaped bands [ Time Frame: 3 years from baseline ]
  18. Presence of reticular drusen/subretinal drusenoid deposits and associated local changes as determined by multimodal imaging [ Time Frame: 3 years from baseline ]
  19. Changes in localized fundus autofluorescence signal alterations [ Time Frame: 3 years from baseline ]
  20. Proportion of subjects with reduction in drusen volume [ Time Frame: 3 years from baseline ]
  21. 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 ]
  22. 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 ]
  23. Presence of quiescent choroidal neovascularisation (CNV) as assessed by optical coherence tomography angiography (OCT-A) (at equipped sites) [ Time Frame: 3 years from baseline ]
  24. OCT-A findings (at equipped sites) [ Time Frame: 3 years from baseline ]
  25. 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 ]
  26. 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 ]
  27. 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 ]
  28. 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 ]
  29. Change in utility index from baseline as measure by the patient-reported outcome measure (PROM) utility index [ Time Frame: 3 years from baseline ]
  30. 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 ]

Biospecimen Retention:   Samples With DNA
Blood samples are collected in the study for two purposes: biobanking and genetic analysis. Detailed instructions on processing and storage of blood samples are provided in a specific manual that will be provided to the clinical sites. Blood samples are stored in a pseudonimysed form.


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   55 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

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
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03349801


Contacts
Contact: Anna Lüning +4922828715624 Anna.Luening@ukbonn.de
Contact: Angela Ferrao +351239480131 macustar@aibili.pt

Locations
Denmark
Righospitalet Copenhagen Recruiting
Copenhagen, Denmark
Principal Investigator: Michael Larsen, Prof.         
France
Centre Hospitalier Intercommunal de Creteil Recruiting
Créteil, France
Principal Investigator: Eric Souied, Prof.         
Centre d'Investigation Clinique Centre National d'Ophtalmologie des Quinze-Vingts Recruiting
Paris, France
Principal Investigator: José-Alain Sahel, Prof.         
Germany
University Hospital Bonn Recruiting
Bonn, Germany
Principal Investigator: Frank Holz, Prof.         
University Hospital Cologne Recruiting
Cologne, Germany
Principal Investigator: Claudia Dahlke, Prof.         
Department of Ophthalmology, University of Freiburg Recruiting
Freiburg, Germany
Principal Investigator: Hansjürgen Agostini, Prof.         
University Eye Hospital Munich Recruiting
Munich, Germany
Principal Investigator: Armin Wolf, Prof.         
St. Franziskus Hospital Recruiting
Münster, Germany
Principal Investigator: Daniel Pauleikhoff, Prof.         
Universtiy Hospital Tuebingen Recruiting
Tübingen, Germany
Principal Investigator: Laura Kuhlwein, Prof.         
University Eye Hospital Ulm Recruiting
Ulm, Germany
Principal Investigator: Gabriele Lang, Prof.         
Italy
Luigi Sacco Hospital Recruiting
Milan, Italy
Principal Investigator: Giovanni Staurenghi, Prof.         
Ospedale San Raffaele Recruiting
Milan, Italy
Principal Investigator: Francesco Bandello, Prof.         
G.B.Bietti Eye Foundation Recruiting
Rom, Italy
Principal Investigator: Maria Cristina Parravano, Prof.         
Netherlands
Radboud University Medical Centre Recruiting
Leiden, Netherlands
Principal Investigator: Camiel Boon, Prof.         
Radboud University Medical Centre Recruiting
Nijmegen, Netherlands
Principal Investigator: Carel Hoyng, Prof.         
Portugal
Centre for Clinical Trials, AIBILI Recruiting
Coimbra, Portugal
Principal Investigator: Rufino Silva, Prof.         
Centro Hospitalar de São João, E.P.E. Recruiting
Porto, Portugal
Principal Investigator: Angela Carneiro, Prof.         
United Kingdom
Queen's University Belfast Recruiting
Belfast, United Kingdom
Principal Investigator: Ruth Hogg, Prof.         
Gloucestershire Hospitals NHS Foundation Trust Recruiting
Gloucester, United Kingdom
Principal Investigator: Emily Fletcher, Prof.         
Moorfields Eye Hospital Recruiting
London, United Kingdom
Principal Investigator: Adnan Tufail, Prof.         
Sponsors and Collaborators
Frank G. Holz
Bayer
Moorfields Eye Hospital NHS Foundation Trust
Novartis Pharmaceuticals
Association for Innovation and Biomedical Research on Light and Image
City, University of London
European Clinical Research Infrastructure Network
La Fondation Voir et Entendre
Hoffmann-La Roche
Radboud University
University of Sheffield
University College, London
Carl Zeiss Meditec AG
Innovative Medicines Initiative
Investigators
Principal Investigator: Frank Holz, Prof. Dr. med. University Hospital, Bonn

Additional Information:
Responsible Party: Frank G. Holz, Prof. Dr. med., University Hospital, Bonn
ClinicalTrials.gov Identifier: NCT03349801     History of Changes
Other Study ID Numbers: ECR-AMD-2017-13
MACUSTAR ( Other Grant/Funding Number: Innovative Medicines Innitiative )
First Posted: November 22, 2017    Key Record Dates
Last Update Posted: December 31, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Frank G. Holz, University Hospital, Bonn:
iAMD
biomarker
clinical endpoint

Additional relevant MeSH terms:
Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases