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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.

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.

SUBMITTER: Terheyden JH

PROVIDER: S-EPMC7368769 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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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.

Terheyden Jan H JH Holz Frank G FG Schmitz-Valckenberg Steffen S Lüning Anna A Schmid Matthias M Rubin Gary S GS Dunbar Hannah H Tufail Adnan A Crabb David P DP Binns Alison A Sánchez Clara I CI Hoyng Carel C Margaron Philippe P Zakaria Nadia N Durbin Mary M Luhmann Ulrich U Zamiri Parisa P Cunha-Vaz José J Martinho Cecília C Leal Sergio S Finger Robert P RP

Trials 20200718 1

<h4>Background</h4>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.<h4>Methods</h4>The protocol describes a low-interventional clinical multicenter study employ ...[more]

PMID: 32682441

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Project description:ImportanceThere is a need for validated clinical end points that are reliably able to quantify potential therapeutic effects of future treatments targeting age-related macular degeneration (AMD) before the onset of serious visual impairment.ObjectiveTo assess the reliability and discriminatory power of 5 simple chart-based visual function (VF) tests as potential measures for clinical trial end points with regulatory and patient-access intention in intermediate AMD (iAMD).Design, setting, and participantsThis international noninterventional study took place at 18 tertiary ophthalmology departments across Europe. Participants were recruited between April 2018 and March 2020 and were identified during routine clinical review. Participants with no AMD and early AMD were recruited from hospital staff, friends, and family of participants with AMD and via referrals from community ophthalmologists and optometrists. The repeatability and discriminatory power of 5 simple chart-based assessments of VF (best-corrected visual acuity [BCVA], low-luminance visual acuity [LLVA], Moorfields Acuity Test [MAT], Pelli-Robson Contrast Sensitivity [CS], and International Reading Speed Test [IReST]) were assessed in a repeated-measures design. VF assessments were performed on day 0 and day 14. Participants with early AMD, iAMD, late AMD, and no AMD were recruited.Main outcomes and measuresIntraclass correlation coefficients (ICCs) and Bland-Altman 95% limits of agreement (LoA) were computed to assess repeatability. Area under the receiver operating characteristic curves (AUCs) determined the discriminatory ability of all measures to classify individuals as having no AMD or iAMD and to differentiate iAMD from its neighboring disease states.ResultsA total of 301 participants (mean [SD] age, 71 [7] years; 187 female participants [62.1%]) were included in the study. Thirty-four participants (11.3%) had early AMD, 168 (55.8%) had iAMD, 43 (14.3%) had late AMD, and 56 (18.6%) had no AMD. ICCs for all VF measures ranged between 0.88 and 0.96 when all participants were considered, indicating good to excellent repeatability. All measures displayed excellent discrimination between iAMD and late AMD (AUC, 0.92-0.99). Early AMD was indistinguishable from iAMD on all measures (AUC, 0.54-0.64). CS afforded the best discrimination between no AMD and iAMD (AUC, 0.77). Under the same conditions, BCVA, LLVA, and MAT were fair discriminators (AUC, 0.69-0.71), and IReST had poor discrimination (AUC, 0.57-0.61).Conclusions and relevanceBCVA, LLVA, MAT, CS, and IReST had adequate repeatability in this multicenter, multiexaminer setting but limited power to discriminate between no AMD and iAMD. The prognostic power of these variables to predict conversion from iAMD to late AMD is being examined in the ongoing longitudinal part of the MACUSTAR study.

Project description:BACKGROUND:To prevent irreversible vision loss in age-related macular degeneration (AMD), it is critical to detect retinal dysfunction before permanent structural loss occurs. In the current study we evaluated a series of visual function tests to identify potential endpoints to detect visual dysfunction in non-advanced AMD. METHODS:A series of visual function tests were performed on 23 non-advanced AMD subjects (AREDS grade 1-4 on simplified scale) and 34 age-matched normals (AREDS grade 0). Tests included some commonly used endpoints such as ETDRS visual acuity (VA), low luminance (LL) 2.0ND ETDRS VA, MNREAD as well as newly developed tests such as the Ora-VCF™ test, Ora-tablet reading test, color sensitivity etc. Differences between the two groups were compared for each test. Test-retest repeatability and reproducibility was assessed on a subset of subjects and percent agreement was calculated. RESULTS:There was no difference in standard ETDRS VA between non-advanced AMD (0.06?±?0.02 logMAR) and normal groups (0.04?±?0.02 logMAR) (p?=?0.57). LL 2.0 ETDRS VA and MNREAD showed no difference between the groups (p?>?0.05). Ora-VCF™ test was significantly worse in the non-advanced AMD group compared to normals (0.67?±?0.07 in AMD; 0.45?±?0.04 in normals, p?=?0.005). Non-advanced AMD subjects also had significantly worse reading performance using the Ora-tablet with LL 2.0ND (114.55?±?11.22 wpm in AMD; 145.17?±?9.55 wpm in normals p?=?0.049). No significant difference between the groups was noted using other tests. Repeatability was 82% for Ora-VCF™ test and 92% for Ora-tablet LL 2.0ND reading. Reproducibility was 89% for both Ora-VCF™ test and Ora-tablet LL 2.0ND reading. CONCLUSION:While there was no significant difference between non-advanced AMD and normal groups using some current common endpoints such as ETDRS VA, LL 2.0 ETDRS VA or MNREAD, Ora-VCF™ test and Ora-tablet LL 2.0ND reading tests were able to identify significant visual dysfunction in non-advanced AMD subjects. These tests show promise as endpoints for AMD studies.

Dataset Information

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.

Publications

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.

Similar Datasets

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