A Non-interventional Study to Assess the Influence of Automated Optical Coherence Tomography Image Enrichment With Segmentation Information on Disease Activity Assessment in Patients Treated With Licensed Anti- VEGF Injections (RAZORBILL)

A Non-interventional Study to Assess the Influence of Automated Optical Coherence Tomography (OCT) Image Enrichment With Segmentation Information on Disease Activity Assessment in Patients Treated With Licensed Anti- VEGF Injections

RAZORBILL is an observational, multicenter, multinational, open-label, study designed primarily to investigate the influence of automated OCT image enrichment with segmentation information on disease activity assessment in nAMD patients treated with licensed anti-VEGFs

Study Overview

• Status: Completed
• Conditions: Neovascular Age-Related Macular Degeneration
• Intervention / Treatment: Drug: brolucizumab; Drug: ranibizumab; Drug: aflibercept

Detailed Description

The main goal of this study is to assess to what degree disease activity assessment is influenced and supported by the enrichment of OCT images with segmentation information (i.e. by identification, highlighting and quantification of pathological fluid compartments associated with neovascular activity).

The study comprises a prospective data collection phase and a retrospective analysis of OCT images phase. The prospective observation period per patient will be up to 12 months.

The study will include 424 patients (naïve patients and patients who have been pre-treated with licensed anti-VEGFs not more than 3 years) being treated for nAMD with brolucizumab, ranibizumab, or aflibercept according to the respective drug label. Patients will be enrolled at approximately 20 centers across 5 countries.

• Study Type: Observational
• Enrollment (Actual): 494

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8G 5E4
      • Novartis Investigative Site
    • Toronto, Ontario, Canada, M8X 2X3
      • Novartis Investigative Site
  • Quebec
    • Montreal, Quebec, Canada, H1V 1G5
      • Novartis Investigative Site
• Germany
  • Bonn, Germany, 53105
    • Novartis Investigative Site
  • Duesseldorf, Germany, 40212
    • Novartis Investigative Site
  • Gottingen, Germany, 37075
    • Novartis Investigative Site
  • Muenster, Germany, 48145
    • Novartis Investigative Site
  • Ulm, Germany, 89075
    • Novartis Investigative Site
  • Baden-Wuerttemberg
    • Ludwigsburg, Baden-Wuerttemberg, Germany, 71638
      • Novartis Investigative Site
• Ireland
  • Waterford, Ireland, 48327
    • Novartis Investigative Site
  • Dublin 9
    • Glasnevin, Dublin 9, Ireland, D09 YN97
      • Novartis Investigative Site
• Italy
  • MI
    • Milano, MI, Italy, 20132
      • Novartis Investigative Site
    • Milano, MI, Italy, 20157
      • Novartis Investigative Site
• Spain
  • Leon, Spain, 24080
    • Novartis Investigative Site
  • Catalunya
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site
    • Barcelona, Catalunya, Spain, 08036
      • Novartis Investigative Site
  • Sevilla
    • Bormujos, Sevilla, Spain, 41930
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 199 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Subjects being treated for nAMD with brolucizumab, ranibizumab, or aflibercept according to the respective drug label.

Description

Inclusion Criteria:

• Diagnosis of nAMD
• Male and Female patients with ≥18 years of age at index
• Receipt of at least one injection of brolucizumab, ranibizumab or aflibercept during the recruitment period
• Signed written informed consent
• Patients for whom a therapy with brolucizumab, ranibizumab or aflibercept is medically indicated according to the respective label
• Intraretinal and/or subretinal fluid affecting the central subfield of the study eye at screening

Exclusion Criteria:

• Patients treated for any other retinal disease than nAMD within 6 months prior to the index date (e.g. patients treated for retinal vein occlusion, diabetic macular oedema, myopic CNV, and have diagnoses of diabetes-related macular degeneration)
• Central subfield of the study eye affected by fibrosis or geographic atrophy or total area of fibrosis >50% of the total lesion in the study eye at screening
• Any active intraocular or periocular infection or active intraocular inflammation in either eye at index date
• Patients who have been on anti-VEGF treatment for longer than 3 years (before index date)
• Patients who have any contraindication and are not eligible for treatment with the chosen anti-VEGF treatment as according to the respective label.
• Any medical or psychological condition, in the treating physician's opinion, which may hinder the patient from participating in this study for the expected 12 months
• Patients participating, in parallel, in an interventional clinical trial
• Patients participating, in parallel, in any other Novartis sponsored NIS generating primary data for an anti-VEGF drug

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Licensed anti-VEGFs; Patients being treated for nAMD with licensed anti-VEGFs

Drug: brolucizumab; There is no treatment allocation. Patients administered Brolucizumab by prescription that have started before inclusion of the patient into the study will be enrolled.; Drug: ranibizumab; There is no treatment allocation. Patients administered Ranibizumab by prescription that have started before inclusion of the patient into the study will be enrolled.; Drug: aflibercept; There is no treatment allocation. Patients administered Aflibercept by prescription that have started before inclusion of the patient into the study will be enrolled.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Odds ratio of disease activity identification from Optical Coherence Tomography (OCTs) with and without automatic augmentation	An odds ratio of disease activity identification from OCTs with and without automatic segmentation will be reported with a 95% confidence interval.	12 months
Degree of agreement in classification of disease activity using segmented OCT images	Degree of agreement in classification of disease activity assessed by Krippendorff's alpha using segmented OCT images	12 months
Degree of agreement in classification of disease activity using non-segmented OCT images	Degree of agreement in classification of disease activity assessed by Krippendorff's alpha using non-segmented OCT images	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess if Discovery is accepted by physicians and whether it can optimize the ophthalmic clinical workflow	Physicians will use a digital solution Discovery for managing imaging data and automatic segmentation of OCT volumes. To understand if such a tool is well suited for its role in its current form, holds value for physicians and can optimize clinical workflow, physicians will be invited to complete questionnaires regarding their user experience.	Month 12
Percentage (%) of patients absent of Subretinal Fluid, Intraretinal Fluid and Pigment Epithelium Detachment	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Month 12
Estimate Central Subfield Thickness (CST) change and correlation with Visual Acuity (VA)	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	12 months
Visual Acuity (VA) change from baseline	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Baseline, month 12
Percentage (%) of patients with ocular and non-ocular adverse events	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	12 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2021
• Primary Completion (Actual): June 28, 2023
• Study Completion (Actual): June 28, 2023

Study Registration Dates

• First Submitted: November 24, 2020
• First Submitted That Met QC Criteria: December 9, 2020
• First Posted (Actual): December 10, 2020

Study Record Updates

• Last Update Posted (Actual): July 27, 2023
• Last Update Submitted That Met QC Criteria: July 25, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: OCT; anti-VEGF; optical coherence tomography; Artificial Intelligence; Machine learning; Neovascular Age-Related Macular Degeneration; nAMD; RAZORBILL; Automatic OCT segmentation
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Wet Macular Degeneration; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Ranibizumab; Aflibercept
• Other Study ID Numbers: CRTH258A2402

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO