Endpoints for clinical trials in ophthalmology

Schmetterer, Leopold; Scholl, Hendrik P. N.; Garhöfer, Gerhard; Janeschitz‐Kriegl, Lucas; Corvi, Federico; Sadda, Srinivas R; Medeiros, Felipe A.

doi:10.1016/j.preteyeres.2022.101160

Cited by 21 publications

(16 citation statements)

References 462 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…21 Assessment of efficacy can include both functional end points, such as best corrected visual acuity, static perimetry, and mobility mazes, as well as structural/anatomic end points, such as central subfield thickness as measured on optical coherence tomography. 39,40 Determining appropriate outcome measures to assess therapeutic effect remains a challenge. Moreover, the slow natural progression characteristic of most retinal diseases dictates that long duration studies (e.g., 12 months of more) are often required to detect a treatment effect.…”

Section: Clinical End Points and Study Durationmentioning

confidence: 99%

“…Health authorities encourage a wide range of potential clinical end points be explored in early‐phase trials, whereas late‐phase trials should focus primary efficacy end points to reflect clinical benefit (e.g., improvement in function or symptoms) 21 . Assessment of efficacy can include both functional end points, such as best corrected visual acuity, static perimetry, and mobility mazes, as well as structural/anatomic end points, such as central subfield thickness as measured on optical coherence tomography 39,40 . Determining appropriate outcome measures to assess therapeutic effect remains a challenge.…”

Section: Clinical Development Considerationsmentioning

confidence: 99%

See 1 more Smart Citation

Clinical Pharmacology Perspective on Development of Adeno‐Associated Virus Vector‐Based Retina Gene Therapy

Ford,

Karatza,

Mody

et al. 2024

Clin Pharma and Therapeutics

View full text Add to dashboard Cite

Adeno‐associated virus (AAV) vector‐based gene therapy is an innovative modality being increasingly investigated to treat diseases by modifying or replacing defective genes or expressing therapeutic entities. With its unique anatomic and physiological characteristics, the eye constitutes a very attractive target for gene therapy. Specifically, the ocular space is easily accessible and is generally considered “immune‐privileged” with a low risk of systemic side effects following local drug administration. As retina cells have limited cellular turnover, a one‐time gene delivery has the potential to provide long‐term transgene expression. Despite the initial success with voretigene neparvovec (Luxturna), the first approved retina gene therapy, there are still challenges to be overcome for successful clinical development of these products and scientific questions to be answered. The current review paper aims to integrate published experience learned thus far for AAV‐based retina gene therapy related to preclinical to clinical translation; first‐in‐human dose selection; relevant bioanalytical assays and strategies; clinical development considerations including trial design, biodistribution and vector shedding, immunogenicity, transgene expression, and pediatric populations; opportunities for model‐informed drug development; and regulatory perspectives. The information presented herein is intended to serve as a guide to inform the clinical development strategy for retina gene therapy with a focus on clinical pharmacology.

show abstract

Section: Clinical End Points and Study Durationmentioning

confidence: 99%

Section: Clinical Development Considerationsmentioning

confidence: 99%

Clinical Pharmacology Perspective on Development of Adeno‐Associated Virus Vector‐Based Retina Gene Therapy

Ford,

Karatza,

Mody

et al. 2024

Clin Pharma and Therapeutics

View full text Add to dashboard Cite

show abstract

“…Secondary endpoints have included mainly functional outcomes, like changes in BCVA in standard and low-luminance conditions, low-luminance deficit, macular sensitivity on microperimetry, reading speed or patient-reported outcome measures (PROM) via questionnaires of quality of life related to vision [ 15 ]. Arguably, functional endpoints are more relevant to patients and are preferrred by regulatory agencies [ 13 ].…”

Section: Designmentioning

confidence: 99%

Methodological Appraisal of Phase 3 Clinical Trials in Geographic Atrophy

Biarnés¹,

Garrell-Salat

Gómez-Benlloch

et al. 2023

Biomedicines

View full text Add to dashboard Cite

Geographic atrophy (GA) secondary to age-related macular degeneration is a common cause of blindness worldwide. Given the recent approval of the first therapy for GA, pegcetacoplan, we critically appraise methodological aspects of the phase 3 clinical trials published so far in this disease in relation to their design, analysis and interpretation. We reviewed some of the key attributes of all phase 3 clinical trials in GA available in the main public registry of clinical trials as of 20 May 2023. The topics discussed included types of endpoints, eligibility criteria, p-value and effect size, study power and sample size, the intention to treat principle, missing data, consistency of results, efficacy–safety balance and application of results. Five phase 3 clinical trials have reported results, either partially or completely: GATHER1, DERBY/OAKS, CHROMA/SPECTRI, SEATTLE and GATE. Although there are many similarities between these trials in terms of endpoints or broad eligibility criteria, they differ in several aspects (metric of the primary endpoint, sample size, type of adverse events, etc.) that can influence the results, which are discussed. Readers should understand key methodological aspects of clinical trials to improve their interpretation. On the other hand, authors should adhere to clinical trial reporting guidelines to communicate what was done and how it was done.

show abstract

“…These challenges are compounded when assessing multidimensional functional vision endpoints such as reading speed [14]. Altogether, these limitations make it difficult to implement these tests in clinical settings or to use them as endpoints in clinical trials [6, 8]. In recent years there have been many attempts to develop novel tests for visual function using computer displays, tablets or smartphones [15].…”

Section: Introductionmentioning

confidence: 99%

VisualR: a novel and scalable solution for assessing visual function using virtual reality

Sozzi,

Groß,

Ljubisic

et al. 2023

Preprint

View full text Add to dashboard Cite

Background: Diagnosis and treatment of progressive eye diseases require effective monitoring of visual structure and function. However, current methods for measuring visual function are limited in accuracy, reliability, and usability. We propose a novel approach that leverages virtual reality (VR) technology to overcome these challenges, enabling more comprehensive measurements of visual function endpoints. Results: We developed VisualR, a low-cost VR-based application that consists of a smartphone app and a simple VR headset. The virtual environment allows precise control of visual stimuli, full control over the field of view, separating visual input to the left and right eyes, controlling visual angles and blocking background visual noise. We developed novel tests for metamorphopsia, contrast sensitivity and reading speed that can be performed by following simple instructions and providing verbal responses to visual cues, without the need for expert supervision. The smartphone app does not require an internet connection, handles all data processing and image display, and all data is stored locally and owned by the user. Conclusion: VisualR demonstrates the feasibility of building a visual function test device using consumer-grade hardware. Eventually, this technology could be used to measure visual function endpoints during clinical development of new treatments and to support disease diagnosis and monitoring. We open-sourced the application code and provide guidelines for creating reliable and user-friendly VR-based tests. We believe VR can open a new paradigm in visual function testing, and invite the wider community to build upon our work.

show abstract

Endpoints for clinical trials in ophthalmology

Cited by 21 publications

References 462 publications

Clinical Pharmacology Perspective on Development of Adeno‐Associated Virus Vector‐Based Retina Gene Therapy

Clinical Pharmacology Perspective on Development of Adeno‐Associated Virus Vector‐Based Retina Gene Therapy

Methodological Appraisal of Phase 3 Clinical Trials in Geographic Atrophy

VisualR: a novel and scalable solution for assessing visual function using virtual reality

Contact Info

Product

Resources

About