The STArgardt Remofuscin Treatment Trial (STARTT): design and baseline characteristics of enrolled Stargardt patients

Open Research Europe · 23 authors, 22 centres

AI SUMMARY

FIDELITY 100%

POPULATIONPatients aged ≥18 years with clinical diagnosis of STGD1, at least two ABCA4 mutations, onset before age 45, qAF8 ≥300 units, and BCVA 0.20-0.80 decimal in the study eye

INTERVENTIONOral remofuscin (soraprazan) 20 mg per day (two 10 mg tablets) taken in the late evening for up to 24 months

COMPARISONPlacebo (cellulose tablets) taken in the same regimen

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AGENT 01 · STRUCTURED SUMMARY

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TL;DR

This paper describes the design and baseline characteristics of the STARTT, a phase II randomized controlled trial evaluating oral remofuscin (soraprazan) for Stargardt disease. At baseline, 87 patients had a median qAF8 of 438 units and median BCVA of 0.50 decimal, with significant impairment in reading speed and vision-related quality of life compared to healthy controls. The trial aims to determine if remofuscin can reduce lipofuscin levels measured by qAF, potentially offering the first treatment for this blinding disease.

Full summary

2,957 CHARS

**Background:** Stargardt disease (STGD1) is an inherited retinal disorder caused by mutations in the ABCA4 gene, leading to accumulation of toxic lipofuscin in retinal pigment epithelium (RPE) cells and progressive vision loss. Currently, no treatment can remove lipofuscin. Remofuscin (soraprazan), originally developed for GERD, has shown ability to remove lipofuscin from RPE in preclinical models. The STARTT is a phase II trial designed to evaluate safety and efficacy of oral remofuscin in STGD1 patients, using quantitative fundus autofluorescence (qAF8) as the primary endpoint.

**Methods:** STARTT is a randomized, double-masked, placebo-controlled study conducted at six European sites. Key inclusion criteria: age ≥18 years, clinical diagnosis of STGD1 with at least two ABCA4 mutations, onset before age 45, qAF8 ≥300 units, and BCVA 0.20-0.80 decimal in the study eye. Patients were randomized 2:1 to remofuscin (20 mg/day) or placebo for up to 24 months. The primary outcome is change in qAF8 from baseline to Month 12 and Month 24. Secondary outcomes include BCVA, low luminance visual acuity (LLVA), low luminance deficit (LLD), reading speed (Radner charts), mesopic microperimetry (mMP), patient-reported outcomes (NEI VFQ-25, FRI Index), central subfield retinal thickness (CSRT), macular volume, and atrophy area. Sample size was calculated assuming a 50-unit treatment difference in qAF8 change with 80% power at α=0.05.

**Key Results:** Between June 2019 and September 2020, 112 patients were screened and 87 enrolled (49 females, 38 males; mean age 35±11 years). Baseline study eye characteristics (median, range): qAF8 438 (210–729) units; BCVA 0.50 (0.13–0.80) decimal; LLVA 0.20 (0.06–0.63); LLD 0.18 (–0.05–0.56); mean retinal sensitivity 20.4 dB (0.0–28.8); atrophy present in 42/83 gradable eyes (51%); CSRT 142 µm (72–265); macular volume 1.65 mm³ (1.13–2.19). NEI VFQ-25 composite score was 72±13, significantly lower than healthy reference for most subscales (p<0.001) except general health (p=0.88), colour vision (p=0.061), and ocular pain (p=0.127). FRI Index mean score was 2.8±0.6; only 17.4% of patients were totally independent (Level 4). Radner reading speed was significantly impaired: maximum reading speed 134±50 words/min vs. 235.71±24.48 in controls (p<0.001); critical print size 0.90±0.24 logRAD vs. 0.085±0.0745 (p<0.001).

**Clinical Implications:** The STARTT is the first trial to use qAF8 as a primary endpoint for lipofuscin reduction in STGD1. Baseline data confirm substantial functional impairment and reduced quality of life even in patients with preserved visual acuity. The trial's comprehensive outcome set, including patient-reported measures, will help validate qAF as a surrogate endpoint and assess clinical benefit. If remofuscin proves effective, it could become the first disease-modifying therapy for STGD1. The study also provides valuable natural history data for future trial design.

PICO

PPOPULATION

Patients aged ≥18 years with clinical diagnosis of STGD1, at least two ABCA4 mutations, onset before age 45, qAF8 ≥300 units, and BCVA 0.20-0.80 decimal in the study eye

IINTERVENTION

Oral remofuscin (soraprazan) 20 mg per day (two 10 mg tablets) taken in the late evening for up to 24 months

OOUTCOME

Primary: change in qAF8 from baseline to Month 12 and Month 24. Secondary: BCVA, LLVA, LLD, reading speed, microperimetry, NEI VFQ-25, FRI Index, CSRT, macular volume, atrophy area, safety parameters

STUDY TYPE

RCT

SPECIALTY

ophthalmology

SUMMARISED BY

AI pipeline

FIDELITY CHECK

100% · A

ORIGINAL PAPER

PMC10445898

The STArgardt Remofuscin Treatment Trial (STARTT): design and baseline characteristics of enrolled Stargardt patients

Open Research Europe

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ABSTRACT

Abstract Background: This report describes the study design and baseline characteristics of patients with Stargardt disease (STGD1) enrolled in the STArgardt Remofuscin Treatment Trial (STARTT). Methods: In total, 87 patients with genetically confirmed STGD1 were randomized in a double-masked, placebo-controlled proof of concept trial to evaluate the safety and efficacy of 20 milligram oral remofuscin for 24 months. The primary outcome measure is change in mean quantitative autofluorescence value of an 8-segment ring centred on the fovea (qAF 8 ). Secondary efficacy variables are best corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), mesopic microperimetry (mMP), spectral domain optical coherence tomography (SD-OCT), reading speed on Radner reading charts, and patient-reported visual function as assessed by the National Eye Institute Visual Functioning Questionnaire 25 (NEI VFQ-25) and Functional Reading Independence (FRI) Index. Results: Mean age of participants was 35±11 years with 49 (56%) female. Median qAF 8 value was 438 Units (range 210-729). Median BCVA and LLVA in decimal units were 0.50 (range 0.13-0.80) and 0.20 (range 0.06-0.63), respectively. The median of the mean retinal sensitivity with mMP was 20.4 dB (range 0.0-28.8). SD-OCT showed median central subfield retinal thickness of 142 µm (range 72-265) and median macular volume of 1.65 mm 3 (range 1.13-2.19). Compared to persons without vision impairment, both reading performance and patient-reported visual function were significantly lower (p<0.001, one sample t-test). Mean reading speed was 108±39 words/minute with logRAD-score of 0.45±0.28. Mean VFQ-25 composite score was 72±13. Mean FRI Index score 2.8±0.6. Conclusions: This trial design may serve as reference for future clinical trials as it explores the utility of qAF 8 as primary outcome measure. The baseline data represent the largest, multi-national, STGD1 cohort to date that underwent standardized qAF imaging, reading speed assessment and vision-related quality of life measures which all contribute to the characterization of STGD1. EudraCT registration: 2018-001496-20 (09/05/2019) Keywords: Stargardt disease, STGD1, ABCA4, Remofuscin, Soraprazan, qAF, quantitative autofluorescence

CITATION EXPORT

Patty PA Dhooge, Philipp T Möller, Camiel JF Boon et al.. The STArgardt Remofuscin Treatment Trial (STARTT): design and baseline characteristics of enrolled Stargardt patients. Open Research Europe. (2022). https://doi.org/10.12688/openreseurope.13872.3

AUTHORS

23 · 22 CENTRES

Patty PA Dhooge, Philipp T Möller, Camiel JF Boon, Andrew J Lotery, Philipp Herrmann, Maurizio Battaglia Parodi, Wolfgang Klein, Mario G Fsadni, Thomas H Wheeler-Schilling, Oliver Jungmann, Hans Müller, Frank G Holz, Steffen Schmitz-Valckenberg, Tobias M Peters, Katarina Stingl, Carel B Hoyng, Victor Chong, Victor Chong, Patty Dhooge, Victor Chong, Patty Dhooge, Xiangrong Kong, Patty Dhooge

1Department of Ophthalmology, Radboud University Nijmegen Medical Centre, Nijmegen, 6500HB, The Netherlands
2Donders Institute for Brain, Cognition and Behaviour, Nijmegen, 6525EN, The Netherlands
3GRADE reading center, Bonn, 53127, Germany
4Department of Ophthalmology, University of Bonn, Bonn, 53127, Germany
5Department of Ophthalmology, Amsterdam University Medical Center, Amsterdam, 1081HV, The Netherlands
6Department of Ophthalmology, Leiden University Medical Center, Leiden, 2333ZA, The Netherlands
7Faculty of Medicine, University of Southampton, Southampton, SO17 1BJ, UK
8Center for Rare Diseases Bonn (ZSEB), University of Bonn, Bonn, 53113, Germany
9Department of Ophthalmology, Ospedale San Raffaele, Milan, 20132, Italy
10Katairo GmbH, Kusterdingen, 72127, Germany
11International Pharm-Med Ltd, Hemel Hempstead, HP1 1LD, UK
12University Eye Hospital, Center for Ophthalmology, Institute for Ophthalmic Research, University of Tübingen, Tübingen, 72076, Germany
13Smerud Medical Research Germany GmbH, Mannheim, D-68161, Germany
14John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, 84132, USA
15Center for Rare Eye Diseases, University of Tübingen, Tübingen, 72076, Germany
1Janssen R&D LLC, Raritan, NJ, USA
1Janssen R&D LLC, Raritan, NJ, USA
1197667, The Netherlands
1Janssen R&D LLC, Raritan, NJ, USA
1197667, The Netherlands
1School of Medicine, Johns Hopkins University, Baltimore, MD, USA
1197667, The Netherlands