Treat & Extend Versus Fixed Dosing With Faricimab for Management of Diabetic Macular Edema: A Pragmatic, Multi-center, Open-label, Randomized, Controlled Trial (INSITE-DME)

June 14, 2024 updated by: McMaster University
This study will assess a pragmatic, treat and extend regimen of faricimab against the standard of a fixed dosing regimen.

Study Overview

Status

Recruiting

Intervention / Treatment

Detailed Description

Diabetes affects 463 million individuals globally and is projected to reach 700 million individuals by 2045. It has been estimated that 27% of patients with diabetes have evidence of diabetic retinopathy and 4.6% of those have diabetic macular edema (DME). DME can be a devastating complication and is a leading cause of vision loss related to diabetic retinopathy. Clinically anti-vascular endothelial growth factor (anti-VEGF) therapy has become the standard of care for treatment of DME. Previous research has led to a gap between real world outcomes and pivotal clinical trial results, highlighting the need for more pragmatic treatment algorithms that are easily replicable in clinical practice. Alternative, pragmatic treatment algorithms have been assessed with the goal of minimizing the burden and costs of DME management, such as the treat and extend (T&E) approach. Currently there is a lack of consensus around a T&E re-treatment algorithm for DME management. Moreover, every T&E trial thus far has used a different re-treatment algorithm which significantly limits clinical applicability.

Our primary objective is to determine if a 4-week pragmatic T&E regime up to Q24W with faricimab versus fixed dosing at Q8W with faricimab produces non-inferior outcomes (mean change in best corrected visual acuity (3.9 letter non-inferiority margin)) from baseline at week 100 for patients diagnosed with CI-DME. All patients with a confirmed diagnosis of diabetes mellitus and a diagnosis of macular edema secondary to diabetic retinopathy as per clinical examination and established measurement cut-off on spectral domain optical coherence tomography (SD-OCT) will be screened for eligibility.

The primary outcome will be mean change in best corrected visual acuity (3.9 letter non-inferiority margin) from baseline at week 100. The best corrected visual acuity for this trial will be assessed using week 100 visit in both treatment arms. The window for the week 100 visit is +/- 2 weeks.

For participants in the fixed dosing arm, follow-up visits will occur every 4 weeks for 6 months and then every 8 weeks during the maintenance phase. For participants in the T&E group, follow-up visits will occur every 4 weeks during initiation phase and then the interval for each subsequent visit will be determined according to the standardized T&E criteria. T&E arm participants will have a forced non treatment visit at Week 100 if not due in dosing schedule.

This trial will generate impactful new data in an area of significant evidence gap regarding the optimal DME management algorithm. The pragmatic trial design will optimize the durability and efficacy of the novel bi-specific antibody, faricimab, and will help establish a clinically useful, easy to replicate T&E strategy aimed at achieving optimal visual outcomes with an individualized treatment regime while minimizing treatment burden.

Study Type

Interventional

Enrollment (Estimated)

446

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

    • New South Wales
      • Albury, New South Wales, Australia, 2640
        • Recruiting
        • Eye Clinic Albury Wodonga
        • Contact:
          • Cherie Byrne
        • Principal Investigator:
          • Dr. Trung Dang
      • Bondi Junction, New South Wales, Australia, 2022
        • Recruiting
        • Eastern Suburbs Eye Specialists
        • Contact:
          • Helen Jeong
        • Principal Investigator:
          • Dr. Matthew Simunovic
      • Hurstville, New South Wales, Australia, 2220
        • Recruiting
        • Retina and Eye Consultants
        • Principal Investigator:
          • Dr. Derek Chan
        • Contact:
          • Julie Coppock
      • Lane Cove, New South Wales, Australia, 2066
        • Recruiting
        • Lane Cove Eye
        • Principal Investigator:
          • Dr. Samantha Fraser-Bell
        • Contact:
          • Xanthe Harrison
      • Liverpool, New South Wales, Australia, 2170
        • Recruiting
        • South West Retina
        • Contact:
          • Tania Tsang
        • Principal Investigator:
          • Dr. Gerald Liew
      • Parramatta, New South Wales, Australia, 2150
        • Recruiting
        • Marsden Eye Specialists
        • Contact:
          • Trish Forsyth
        • Principal Investigator:
          • Dr. Jennifer Arnold
      • Strathfield, New South Wales, Australia, 2135
        • Recruiting
        • Strathfield Retina Clinic
        • Contact:
          • Sarrvesa Singh
        • Principal Investigator:
          • Dr. Hemal Mehta
      • Sydney, New South Wales, Australia, 2000
        • Recruiting
        • Sydney Retina
        • Contact:
          • Thomas Hong
        • Principal Investigator:
          • Dr. Andrew Chang
      • Sydney, New South Wales, Australia, 2000
        • Recruiting
        • South Eastern Sydney Health
        • Contact:
          • Sharon McKenzie
        • Principal Investigator:
          • Dr. Samantha Fraser-Bell
    • Queensland
      • Woolloongabba, Queensland, Australia, 4012
        • Recruiting
        • Queensland Eye Institute
        • Contact:
          • Brett Caldwell
        • Principal Investigator:
          • Dr. Abhishek Sharma
    • South Australia
      • Adelaide, South Australia, Australia, 5000
        • Recruiting
        • Adelaide Eye & Retina Centre
        • Contact:
          • Kerin Haywood
        • Principal Investigator:
          • Dr. Jaghit Gilhotra
    • Tasmania
      • Hobart, Tasmania, Australia, 7008
        • Recruiting
        • Hobart Eye Surgeons
        • Contact:
          • Beverley Curry
        • Principal Investigator:
          • Dr. Nitin Verma
    • Victoria
      • East Melbourne, Victoria, Australia, 3002
        • Recruiting
        • Centre for Eye Research Australia
        • Contact:
          • Thuy Chau
        • Principal Investigator:
          • Dr. Robyn Troutbeck
      • Rowville, Victoria, Australia, 3178
        • Recruiting
        • Retina Specialists Victoria
        • Contact:
          • Thuy Chau
        • Principal Investigator:
          • Dr. Sanjeewa Wickremasinghe
    • Western Australia
      • Nedlands, Western Australia, Australia, 6009
        • Recruiting
        • Lions Eye Institute Limited
        • Contact:
          • JoAnne Forest
        • Principal Investigator:
          • Dr. Fred Chen
    • Alberta
      • Calgary, Alberta, Canada, T2H 0C8
        • Recruiting
        • Calgary Retina Consultants
        • Contact:
          • Norah Hanna
        • Principal Investigator:
          • Geoff Williams, MD
      • Calgary, Alberta, Canada, T5H 0X5
        • Recruiting
        • Alberta Retina Consultants
        • Contact:
          • Heather Pilisko
        • Principal Investigator:
          • Matthew Tennant, MD
    • British Columbia
      • New Westminster, British Columbia, Canada, V3L 5H1
        • Recruiting
        • Retina Surgical Associates
        • Contact:
          • Ramil Lovete
        • Principal Investigator:
          • Dr. Robert Gizicki
      • Vancouver, British Columbia, Canada, V5Z 1K1
        • Recruiting
        • West Coast Retina
        • Contact:
          • Yumi Ohashi
        • Contact:
          • Garnet Elvena
        • Principal Investigator:
          • David Albiani, MD
      • Vancouver, British Columbia, Canada, V5Z 1M9
        • Recruiting
        • UBC Eye Centre, Vancouver General Hospital
        • Principal Investigator:
          • Dr. Wai-Ching Lam
        • Contact:
          • Namita Ramdin
    • Ontario
      • Hamilton, Ontario, Canada, L8G 5E4
        • Recruiting
        • The Research Institute of St. Joe's Hamilton
        • Contact:
        • Contact:
        • Principal Investigator:
          • Varun Chaudhary, MD, FRCS(C)
      • London, Ontario, Canada, N6A 4V2
        • Recruiting
        • St. Joseph's Healthcare London
        • Contact:
          • Julie Duncan
        • Principal Investigator:
          • Dr. Tom Sheidow
      • Ottawa, Ontario, Canada, K2B 7E9
        • Recruiting
        • Retina Institute of Ottawa
        • Contact:
          • Shannon MacDonald
        • Contact:
          • Kayleigh Corbet
        • Principal Investigator:
          • Raman Tuli
      • Ottawa, Ontario, Canada, K1H 8L6
        • Withdrawn
        • University of Ottawa Eye Institute
      • Toronto, Ontario, Canada, M3C 0G9
        • Recruiting
        • Toronto Retina Institute
        • Contact:
          • Paviya Navanathan
        • Principal Investigator:
          • Dr. David Chow
      • Toronto, Ontario, Canada, M8X 2X3
        • Recruiting
        • Vitreous Retina Macula Specialists of Toronto
        • Contact:
          • Tatjana Sukovic
        • Principal Investigator:
          • Netan Choudhry, MD
      • Toronto, Ontario, Canada, M5T 2S8
        • Recruiting
        • UHN Toronto Western Hospital
        • Contact:
          • Judy Hung
        • Principal Investigator:
          • Dr. Michael Brent
      • Toronto, Ontario, Canada, M5B 1W8
        • Recruiting
        • Sunnybrook Health Sciences Centre
        • Contact:
          • Faryal Maniyali
        • Principal Investigator:
          • Dr. Peter Kertes
    • Quebec
      • Montréal, Quebec, Canada, H1T 2M4
        • Recruiting
        • Maisonneuve-Rosemont Hospital
        • Contact:
          • Shigufa Kahn
        • Principal Investigator:
          • Dr. Cynthia Qian
    • England
      • Bradford, England, United Kingdom
        • Recruiting
        • Bradford Royal Infirmary
        • Contact:
          • Nicola Hawes
        • Principal Investigator:
          • Faruque Ghanchi
      • Bristol, England, United Kingdom
        • Recruiting
        • University Hospitals Bristol-Weston
        • Contact:
          • Sarah Sulaiman
        • Principal Investigator:
          • Oluwaniyi Eke
      • Frimley, England, United Kingdom
        • Not yet recruiting
        • Frimley Health
        • Contact:
          • Clare Denford
        • Principal Investigator:
          • Manju Chandran
      • Liverpool, England, United Kingdom
        • Recruiting
        • Liverpool University Hospitals
        • Principal Investigator:
          • Ian Pearce
      • London, England, United Kingdom
        • Recruiting
        • London North West University
        • Contact:
          • Elena Neata
        • Principal Investigator:
          • Christiana Dinah
      • London, England, United Kingdom
        • Recruiting
        • Moorfields Eye Hospital
        • Contact:
          • Asma Burale
        • Principal Investigator:
          • Sridevi Thottarath
      • London, England, United Kingdom
        • Recruiting
        • King's College Hospital
        • Contact:
          • Nikki Timson
        • Principal Investigator:
          • Haralabos Eleftheriadis
      • Manchester, England, United Kingdom
        • Not yet recruiting
        • Manchester University
        • Contact:
          • Stephanie Clarke
        • Principal Investigator:
          • Romi Chabbra
      • Wolverhampton, England, United Kingdom
        • Recruiting
        • The Royal Wolverhampton
        • Contact:
          • Paros Papadopoulos
        • Principal Investigator:
          • Niro Narendran
    • California
      • Modesto, California, United States, 95356
        • Recruiting
        • Retinal Consultants Medical Group Inc.
        • Contact:
          • Rashin Sedighi
        • Principal Investigator:
          • Cameron Pole
      • Sacramento, California, United States, 95825
        • Recruiting
        • Vitreo-Retina Medical Group
        • Contact:
          • Rashin Sedighi
        • Principal Investigator:
          • Joel Pearlman
    • Illinois
      • Oak Forest, Illinois, United States, 60452
        • Recruiting
        • University Retina and Macula Associates
        • Principal Investigator:
          • Veeral Sheth, MD
        • Contact:
          • Cindy Vallejo
    • Louisiana
      • West Monroe, Louisiana, United States, 71291
        • Recruiting
        • Eye Associates of Northeast Louisiana Dba Haik Humble Eye Center
        • Contact:
          • Sharoon David
        • Principal Investigator:
          • Ruben Grigorian, MD
    • Mississippi
      • Jackson, Mississippi, United States, 39202
        • Recruiting
        • Mississippi Retina Associates
        • Contact:
          • Anne Britt
        • Principal Investigator:
          • Michael Borne
    • Texas
      • Austin, Texas, United States, 78705
        • Recruiting
        • Austin Retina Associates
        • Contact:
          • Phillip Le
        • Principal Investigator:
          • Robert Wong
      • Beaumont, Texas, United States, 77707
        • Recruiting
        • Retina Consultants of Texas
        • Contact:
          • Jessica Hamilton
        • Principal Investigator:
          • William Pearce
      • Bellaire, Texas, United States, 77401
        • Recruiting
        • Retina Consultants of Houston, dba Retina Consultants of Texas
        • Principal Investigator:
          • Charles Wykoff, MD
        • Contact:
          • Sheryl Hanson
      • Bellaire, Texas, United States, 77401
        • Recruiting
        • Retina & Vitreous of Texas
        • Contact:
          • Kendra Wicks
        • Principal Investigator:
          • Emmanuel Chang
      • McAllen, Texas, United States, 78503
        • Recruiting
        • Valley Retina Institute
        • Principal Investigator:
          • Victor H Gonzalez, MD
        • Contact:
          • Vaney Capetillo
      • San Antonio, Texas, United States, 78240
        • Recruiting
        • Retina Consultants of Houston, dba Retina Consultants of Texas
        • Contact:
          • Jonathan San Roman
        • Contact:
          • Emily Gonzales
        • Principal Investigator:
          • Jeremiah Brown, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age ≥ 18 years
  2. Diagnosis of diabetes mellitus (type 1 or type 2).
  3. Macular thickening secondary to DME (CI-DME) involving the center of the fovea on Optical Coherence Tomography - Central subfield thickness (CST) ≥ 325 μm on Spectralis at screening.***
  4. Visual impairment due to DME, with best corrected visual acuity of 80 to 20 letters (Snellen VA 20/25 - 20/400).
  5. Media clarity, pupillary dilation, and individual cooperation sufficient for adequate OCT and fundus photographs.
  6. Hemoglobin A1c must be <10% within 2 months prior to 1st study treatment.
  7. Provide signed informed consent.

Exclusion Criteria:

  1. Active or history of ocular inflammation or suspected/active ocular infection in either eye.
  2. High-risk proliferative diabetic retinopathy in the study eye.**
  3. Tractional retinal detachment, preretinal fibrosis or visually significant epiretinal membrane involving the macula.
  4. Uncontrolled glaucoma (intraocular pressure >30 with or without medications).
  5. Any intravitreal, periocular or implant corticosteroids within 26 weeks (6 months) before day 1 or any use of Iluvien implants.
  6. Treatment with Panretinal photocoagulation (PRP) within 12 weeks before day 1.
  7. Treatment with macular laser.
  8. Any cataract surgery or any other intraocular surgery within 12 weeks before day 1.
  9. Macular edema in study eye due to a cause other than DME.
  10. If clinical exam and/or OCT and/or wide-field fluorescein angiography (WF-FA) suggest that (a) macular edema is considered to be related to ocular surgery such as cataract extraction or (b) if primary cause for macular edema is vitreoretinal interface abnormalities (e.g. a taut posterior hyaloid or epiretinal membrane).
  11. Any ocular condition is present such that visual acuity loss would not improve from resolution of macular edema in opinion of the investigator (e.g. foveal atrophy, pigment abnormalities, dense subfoveal hard exudates, nonretinal condition)
  12. Any history of ocular conditions that might affect macular edema (e.g. vein occlusion, idiopathic or infectious or non-infectious uveitis, ocular inflammatory disease, neovascular glaucoma etc.)
  13. Women of child-bearing potential who are lactating, pregnant, or intending to become pregnant within the next 100 weeks.
  14. Current or anticipated incarceration.
  15. Terminal illness with expected survival less than 100 weeks.
  16. Known hypersensitivity to faricimab or any of the excipients in the faricimab injection.
  17. Currently enrolled in a study that does not permit co-enrollment.
  18. Unable to obtain informed consent due to language or other operational barriers.
  19. Anticipated problems, in the judgment of the site investigator, maintaining compliance with the protocol, including attending study visits, completing assessments or procedures.
  20. Prior enrollment in this trial.
  21. Other reason to exclude the patient, as approved by the sponsor and site investigator.
  22. Previous treatment with anti-VEGF and:

    • <12 weeks prior to day 1 (washout period).*or,
    • Diagnosis of DME is > 2 years of enrollment or,
    • Do not have a demonstrated response to anti-VEGF treatment based on clinical discretion.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treat and Extend
Participants randomized to the T&E Arm will initially receive 6 milligrams (mg) faricimab intravitreal (IVT) injections monthly (28d +/-7 days), with treatment intervals increased/extended, reduced, or maintained based on CST assessments, until week 100.
Faricimab will be administered via intravitreal injection.
Other: Control/Usual Care Arm
Participants in the control arm will receive 6 milligrams (mg) faricimab intravitreal (IVT) injections monthly (28d +/-7 days), for 6 treatments. Afterwards, participants will continue to receive 6mg faricimab IVT every 8 weeks until week 100.
Faricimab will be administered via intravitreal injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Best Corrected Visual Acuity
Time Frame: Baseline to Week 100
Change in best corrected visual acuity (3.9 letter non-inferiority margin)
Baseline to Week 100

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Decrease in Diabetic Retinopathy Severity Score
Time Frame: Baseline to Week 100
A 2-step improvement in diabetic retinopathy severity score
Baseline to Week 100
Decrease in Diabetic Retinopathy Severity Score
Time Frame: Baseline to Week 100
A 3-step improvement in diabetic retinopathy severity score
Baseline to Week 100
Change in Central Subfield Thickness
Time Frame: Baseline to Week 100
Change in central subfield thickness on OCT
Baseline to Week 100
Change in Vision Related Quality of Life
Time Frame: Baseline to Week 100
Change in vision-related quality of life (VFQ-25)
Baseline to Week 100
Change in Letters of Vision
Time Frame: Baseline to Week 100
Gaining or losing ≥5, ≥10, or ≥15 letters of vision
Baseline to Week 100
Absence of Diabetic Macular Edema
Time Frame: Week 100
Absence of diabetic macular edema in the study eye
Week 100
Absence of Intraretinal Fluid (IRF)
Time Frame: Week 100
Absence of intraretinal fluid (IRF) in the study eye
Week 100
Dosing Interval
Time Frame: Week 100
Dosing interval at week 100
Week 100
Presence of Safety Outcomes
Time Frame: Baseline to Week 100
Safety outcomes (ocular and systemic AEs and SAEs)
Baseline to Week 100

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Collaborators

Investigators

  • Principal Investigator: Dr. Varun Chaudhary, MD, FRCS(C), McMaster University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2023

Primary Completion (Estimated)

August 1, 2026

Study Completion (Estimated)

August 1, 2026

Study Registration Dates

First Submitted

November 2, 2022

First Submitted That Met QC Criteria

November 2, 2022

First Posted (Actual)

November 9, 2022

Study Record Updates

Last Update Posted (Actual)

June 17, 2024

Last Update Submitted That Met QC Criteria

June 14, 2024

Last Verified

June 1, 2024

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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