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\u2014MACUSTAR

Jan Henrik Terheyden ,Anna Lüning,Clara I Sánchez,Robert P Finger,Alison Binns,Hannah Dunbar,Gary S Rubin,Sérgio Leal ,Adnan Tufail,Nadia Zakaria,Parisa Zamiri,Frank G Holz,Mary K Durbin ,José Cunha-Vaz ,Matthias Schmid,Philippe Margaron,Clarisse Martinho ,Ulrich F O Luhmann ,David P Crabb,Steffen Schmitz-Valckenberg,Carel B Hoyng

doi:10.1186/s13063-020-04595-6

Abstract

BackgroundThere 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.MethodsThe 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.DiscussionThe 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 registrationClinicalTrials.gov NCT03349801. Registered on 22 November 2017

Highlights

There is an unmet need for treatment options in intermediate age-related macular degeneration
Regulator interaction A joint scientific advice procedure with the European Medicines Agency (EMA), Food and Drug Administration (FDA), and Health Technology Assessment (HTA) bodies on the proposed MACUSTAR clinical study design and selected outcome measures was initiated by the MACUSTAR consortium in 2016 prior to study start
An ongoing dialogue with regulators will ensure that regulator expectations and feedback are met and increase the likelihood of developed outcomes being accepted as clinical endpoints by regulators

Summary

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

Background

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Procedures

Findings

Availability of data and materials Not applicable