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)

• ClinicalTrials.gov Identifier: NCT04662944
• Recruitment Status: Active, not recruiting
• First Posted: December 10, 2020
• Last Update Posted: April 18, 2023
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment
Neovascular Age-Related Macular Degeneration	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 Design

• Study Type: Observational
• Actual Enrollment: 494 participants
• Observational Model: Cohort
• Time Perspective: Other
• Official Title: 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
• Actual Study Start Date: February 23, 2021
• Estimated Primary Completion Date: June 30, 2023
• Estimated Study Completion Date: June 30, 2023

Groups and Cohorts

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.

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Assess if Discovery is accepted by physicians and whether it can optimize the ophthalmic clinical workflow [ Time Frame: Month 12 ]
   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.
2. Percentage (%) of patients absent of Subretinal Fluid, Intraretinal Fluid and Pigment Epithelium Detachment [ Time Frame: Month 12 ]
   Detailed Outcome Measure will be defined in the Statistical Analysis Plan
3. Estimate Central Subfield Thickness (CST) change and correlation with Visual Acuity (VA) [ Time Frame: 12 months ]
   Detailed Outcome Measure will be defined in the Statistical Analysis Plan
4. Visual Acuity (VA) change from baseline [ Time Frame: Baseline, month 12 ]
   Detailed Outcome Measure will be defined in the Statistical Analysis Plan
5. Percentage (%) of patients with ocular and non-ocular adverse events [ Time Frame: 12 months ]
   Detailed Outcome Measure will be defined in the Statistical Analysis Plan

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 199 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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.

Criteria

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

Contacts and Locations

Locations

Canada, Ontario

Novartis Investigative Site

Hamilton, Ontario, Canada, L8G 5E4

Novartis Investigative Site

Toronto, Ontario, Canada, M8X 2X3

Canada, Quebec

Novartis Investigative Site

Montreal, Quebec, Canada, H1V 1G5

Germany

Novartis Investigative Site

Ludwigsburg, Baden-Wuerttemberg, Germany, 71638

Novartis Investigative Site

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

Ireland

Novartis Investigative Site

Glasnevin, Dublin 9, Ireland, D09 YN97

Novartis Investigative Site

Waterford, Ireland, 48327

Italy

Novartis Investigative Site

Milano, MI, Italy, 20132

Novartis Investigative Site

Milano, MI, Italy, 20157

Spain

Novartis Investigative Site

Barcelona, Catalunya, Spain, 08035

Novartis Investigative Site

Barcelona, Catalunya, Spain, 08036

Novartis Investigative Site

Bormujos, Sevilla, Spain, 41930

Novartis Investigative Site

Leon, Spain, 24080

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

More Information

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT04662944
• Other Study ID Numbers: CRTH258A2402
• First Posted: December 10, 2020
• Last Update Posted: April 18, 2023
• Last Verified: April 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

nAMD; Neovascular Age-Related Macular Degeneration; anti-VEGF; RAZORBILL; optical coherence tomography; OCT; Artificial Intelligence; Machine learning; Automatic OCT segmentation

Additional relevant MeSH terms:

Macular Degeneration; Wet Macular Degeneration; Retinal Degeneration; Retinal Diseases; Eye Diseases; Ranibizumab; Aflibercept; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Antineoplastic Agents