Clinical study protocol for a low-interventional study in intermediate age-related macular degeneration developing novel clinical endpoints for interventional clinical trials with a regulatory and patient access intention-MACUSTAR

Jan H Terheyden; Frank G Holz; Steffen Schmitz-Valckenberg; Anna Lüning; Matthias Schmid; Gary S Rubin; Hannah Dunbar; Adnan Tufail; David P Crabb; Alison Binns; Clara I Sánchez; Carel Hoyng; Philippe Margaron; Nadia Zakaria; Mary Durbin; Ulrich Luhmann; Parisa Zamiri; José Cunha-Vaz; Cecília Martinho; Sergio Leal; Robert P Finger; MACUSTAR consortium

doi:10.1186/s13063-020-04595-6

Clinical study protocol for a low-interventional study in intermediate age-related macular degeneration developing novel clinical endpoints for interventional clinical trials with a regulatory and patient access intention-MACUSTAR

Trials. 2020 Jul 18;21(1):659. doi: 10.1186/s13063-020-04595-6.

Authors

Jan H Terheyden¹, Frank G Holz¹, Steffen Schmitz-Valckenberg¹, Anna Lüning¹, Matthias Schmid², Gary S Rubin³, Hannah Dunbar³, Adnan Tufail⁴, David P Crabb⁵, Alison Binns⁵, Clara I Sánchez⁶, Carel Hoyng⁶, Philippe Margaron⁷, Nadia Zakaria⁷, Mary Durbin⁸, Ulrich Luhmann⁹, Parisa Zamiri⁷, José Cunha-Vaz¹⁰, Cecília Martinho¹⁰, Sergio Leal¹¹, Robert P Finger¹²; MACUSTAR consortium

Collaborators

MACUSTAR consortium:
P Basile, C Behning, M Berger, A Binns, M Böttger, C Bouchet, J E Brazier, T Butt, C Carapezzi, J Carlton, A Charil, R Coimbra, S Nunes, D Crabb, J Cunha-Vaz, H Dunbar, M Durbin, R Finger, F Holz, C Hoyng, J Krätzschmar, S Leal, U Luhmann, A Lüning, Ph Margaron, C Martinho, B Melício, S Mohand-Saïd, D Rowen, G S Rubin, J Sahel, C I Sánchez, D Sanches Fernandes, M Schmid, S Schmitz-Valckenberg, A Skelly, L Stöhr, D Taylor, J Terheyden, A Tufail, L Vieweg, L Wintergerst, C Wojek, N Zakaria, P Zamiri

Affiliations

¹ Department of Ophthalmology, University Hospital Bonn, Ernst-Abbe-Str. 2, 53127, Bonn, Germany.
² Institute for Medical Biometry, Informatics and Epidemiology, Medical Faculty, University of Bonn, Bonn, Germany.
³ UCL Institute of Ophthalmology, University College London, London, UK.
⁴ Moorfields Eye Hospital, London, UK.
⁵ Division of Optometry and Visual Science, School of Health Sciences, City, University of London, London, UK.
⁶ Radboud University Medical Center, Nijmegen, Netherlands.
⁷ Novartis Pharma AG, Basel, Switzerland.
⁸ Carl Zeiss Meditec AG, Dublin, CA, USA.
⁹ Roche Pharmaceutical Research and Early Development, Translational Medicine Ophthalmology, Roche Pharma Research and Early Development, Roche Innovation Center Basel, Basel, Switzerland.
¹⁰ Association for Innovation and Biomedical Research on Light and Image, Coimbra, Portugal.
¹¹ Bayer AG, Berlin, Germany.
¹² Department of Ophthalmology, University Hospital Bonn, Ernst-Abbe-Str. 2, 53127, Bonn, Germany. robert.finger@ukbonn.de.

Abstract

Background: There is an unmet need for treatment options in intermediate age-related macular degeneration (iAMD). However, for any new interventions to be tested in clinical trials, novel currently unavailable clinical endpoints need to be developed. Thus, the MACUSTAR study aims to develop and evaluate functional, structural, and patient-reported candidate endpoints for use in future iAMD trials.

Methods: The protocol describes a low-interventional clinical multicenter study employing a novel two-part design. The cross-sectional part (total duration, 1 month) and the longitudinal part (total duration, 36 months) include participants with iAMD and control groups with early/late/no AMD. The cross-sectional part's primary objective is a technical evaluation of functional, structural, and patient-reported candidate outcomes. The longitudinal part's primary objective is to assess the prognostic power of changes in functional, structural, and patient-reported outcomes for progression from iAMD to late AMD. All data will be used to support a biomarker qualification procedure by regulatory authorities.

Discussion: The MACUSTAR study characterizes and evaluates much needed novel functional, structural, and patient-reported endpoints for future clinical trials in iAMD and will improve our understanding of the natural history and prognostic markers of this condition.

Trial registration: ClinicalTrials.gov NCT03349801 . Registered on 22 November 2017.

Keywords: Clinical endpoint; Clinical study protocol; Disease progression; Intermediate age-related macular degeneration.

MeSH terms

Clinical Trials as Topic
Cross-Sectional Studies
Endpoint Determination*
Humans
Longitudinal Studies
Macular Degeneration* / diagnosis
Macular Degeneration* / therapy
Multicenter Studies as Topic
Observational Studies as Topic
Research Design*
Tomography, Optical Coherence

Associated data

ClinicalTrials.gov/NCT03349801

Grants and funding

116076/Innovative Medicines Initiative 2 Joint Undertaking