Study of the Efficacy and Safety of Intravitreal (IVT) Aflibercept for the Improvement of Moderately Severe to Severe Nonproliferative Diabetic Retinopathy (NPDR) (PANORAMA)

July 15, 2020 updated by: Regeneron Pharmaceuticals

A Phase 3, Double-Masked, Randomized Study of the Efficacy and Safety of Intravitreal Aflibercept Injection in Patients With Moderately Severe to Severe Nonproliferative Diabetic Retinopathy

The primary objective of the study is to assess the efficacy of intravitreal (IVT) aflibercept compared to sham treatment in the improvement of moderately severe to severe nonproliferative diabetic retinopathy (NPDR).

The secondary objectives of the study are:

  • To characterize the safety of IVT aflibercept in patients with moderately severe to severe NPDR
  • To determine if IVT aflibercept will prevent the worsening of diabetic retinopathy and reduce the incidence of DME
  • To determine the anatomic effects of IVT aflibercept in patients with moderately severe to severe NPDR

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

402

Phase

  • Phase 3

Contacts and Locations

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

Study Locations

  • Germany
    • Hesse
      • Marburg, Hesse, Germany, 35043
        • Regeneron Study Site
    • North Rhine-Westphalia
      • Münster, North Rhine-Westphalia, Germany, 48145
        • Regeneron Study Site
    • Saxony
      • Leipzig, Saxony, Germany, 04103
        • Regeneron Study Site
  • Hungary
    • Csongrad
      • Szeged, Csongrad, Hungary, 6720
        • Regeneron Study Site
    • Hajdu-Bihar
      • Debrecen, Hajdu-Bihar, Hungary, 4032
        • Regeneron Study Site
    • Pest
      • Budapest, Pest, Hungary, 1062
        • Regeneron Study Site
      • Budapest, Pest, Hungary, 1106
        • Regeneron Study Site
    • Zala
      • Zalaegerszeg, Zala, Hungary, 8900
        • Regeneron Study Site
  • Japan
      • Kagoshima, Japan, 890-8520
        • Regeneron Study Site
      • Nagasaki, Japan, 852-8501
        • Regeneron Study Site
    • Hokkaido
      • Asahikawa, Hokkaido, Japan, 078-8510
        • Regeneron Study Site
    • Hyogo
      • Amagasaki, Hyogo, Japan, 660-8550
        • Regeneron Study Site
    • Nagano
      • Matsumoto, Nagano, Japan, 390-8621
        • Regeneron Study Site
    • Tokyo
      • Chiyoda, Tokyo, Japan, 101-8309
        • Regeneron Study Site
  • Puerto Rico
      • Arecibo, Puerto Rico, 00613
        • Regeneron Study Site
      • San Juan, Puerto Rico, 00907
        • Regeneron Study Site
  • United Kingdom
      • London, United Kingdom, EC1V 2PD
        • Regeneron Study Site
    • Surrey
      • Camberley, Surrey, United Kingdom, GU16 7UJ
        • Regeneron Study Site
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85020
        • Regeneron Study Site
      • Tucson, Arizona, United States, 85704
        • Regeneron Study Site
    • California
      • Arcadia, California, United States, 91007
        • Regeneron Study Site
      • Beverly Hills, California, United States, 90211
        • Regeneron Study Site
      • Encino, California, United States, 91436
        • Regeneron Study Site
      • Fullerton, California, United States, 92835
        • Regeneron Study Site
      • La Jolla, California, United States, 92093
        • Regeneron Study Site
      • Mountain View, California, United States, 94040
        • Regeneron Study Site
      • Oakland, California, United States, 94609
        • Regeneron Study Site
      • Oceanside, California, United States, 92056
        • Regeneron Study Site
      • Sacramento, California, United States, 95841
        • Regeneron Study Site
    • Colorado
      • Colorado Springs, Colorado, United States, 80909
        • Regeneron Study Site
      • Golden, Colorado, United States, 80401
        • Regeneron Study Site
    • Connecticut
      • New London, Connecticut, United States, 06320
        • Regeneron Study Site
    • Florida
      • Altamonte Springs, Florida, United States, 32701
        • Regeneron Study Site
      • Deerfield Beach, Florida, United States, 33064
        • Regeneron Study Site
      • Fort Myers, Florida, United States, 33912
        • Regeneron Study Site
      • Lakeland, Florida, United States, 33805
        • Regeneron Study Site
      • Largo, Florida, United States, 33770
        • Regeneron Study Site
      • Melbourne, Florida, United States, 32901
        • Regeneron Study Site
      • Miami, Florida, United States, 33126
        • Regeneron Study Site
      • Miami, Florida, United States, 33143
        • Regeneron Study Site
      • Orlando, Florida, United States, 32806
        • Regeneron Study Site
      • Plantation, Florida, United States, 33324
        • Regeneron Study Site
      • Tallahassee, Florida, United States, 32308
        • Regeneron Study Site
      • Tampa, Florida, United States, 33612
        • Regeneron Study Site
      • Winter Haven, Florida, United States, 33880
        • Regeneron Study Site
    • Georgia
      • Marietta, Georgia, United States, 30060
        • Regeneron Study Ssites
      • Tucker, Georgia, United States, 30084
        • Regeneron Study Site
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Regeneron Study Site
      • Oak Forest, Illinois, United States, 60452
        • Regeneron Study Site
    • Indiana
      • Indianapolis, Indiana, United States, 46290
        • Regeneron Study Site
      • New Albany, Indiana, United States, 47150
        • Regeneron Study Site
    • Kentucky
      • Lexington, Kentucky, United States, 40509
        • Regeneron Study Site
    • Maryland
      • Baltimore, Maryland, United States, 21204
        • Regeneron Study Site
      • Baltimore, Maryland, United States, 21209
        • Regeneron Study Siste
      • Baltimore, Maryland, United States, 21287
        • Regeneron Study Site
      • Hagerstown, Maryland, United States, 21740
        • Regeneron Study Site
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Regeneron Study Site
    • Nevada
      • Henderson, Nevada, United States, 89052
        • Regeneron Study Site
    • New Jersey
      • Bloomfield, New Jersey, United States, 07003
        • Regeneron Study Site
    • New Mexico
      • Albuquerque, New Mexico, United States, 87109
        • Regeneron Study Site
    • North Carolina
      • Asheville, North Carolina, United States, 28803
        • Regeneron Study Site
      • Charlotte, North Carolina, United States, 28210
        • Regeneron Study Site
    • Ohio
      • Columbus, Ohio, United States, 43212
        • Regeneron Study Site
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Regeneron Study Site
    • Oregon
      • Medford, Oregon, United States, 97504
        • Regeneron Study Site
    • Pennsylvania
      • Kingston, Pennsylvania, United States, 18704
        • Regeneron Study Site
      • Philadelphia, Pennsylvania, United States, 19107
        • Regeneron Study Site
    • South Carolina
      • Florence, South Carolina, United States, 29501
        • Regeneron Study Site
      • Ladson, South Carolina, United States, 29456
        • Regeneron Study Site
      • West Columbia, South Carolina, United States, 29169
        • Regeneron Study Site
    • South Dakota
      • Rapid City, South Dakota, United States, 57701
        • Regeneron Study Site
    • Tennessee
      • Chattanooga, Tennessee, United States, 37421
        • Regeneron Study Site
      • Germantown, Tennessee, United States, 38138
        • Regeneron Study Site
      • Nashville, Tennessee, United States, 37203
        • Regeneron Study Site
      • Nashville, Tennessee, United States, 37232
        • Regeneron Study Site
    • Texas
      • Abilene, Texas, United States, 79606
        • Regeneron Study Site
      • Austin, Texas, United States, 78705
        • Regeneron Study Site 1
      • Austin, Texas, United States, 78705
        • Regeneron Study Site 2
      • Dallas, Texas, United States, 75231
        • Regeneron Study Site
      • Harlingen, Texas, United States, 78559
        • Regeneron Study Site
      • Houston, Texas, United States, 77030
        • Regeneron Study Site
      • San Antonio, Texas, United States, 78240
        • Regeneron Study Site
      • The Woodlands, Texas, United States, 77384
        • Regeneron Study Site
      • Willow Park, Texas, United States, 76087
        • Regeneron Study Site
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • Regeneron Study Site
    • Vermont
      • Burlington, Vermont, United States, 05401
        • Regeneron Study Site
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Regeneron Study Site
    • Washington
      • Spokane, Washington, United States, 99204
        • Regeneron Study Site
    • West Virginia
      • Morgantown, West Virginia, United States, 26506
        • Regeneron Study Site

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

Genders Eligible for Study

All

Description

Key Inclusion Criteria:

  1. Men or women ≥18 years of age with type 1 or 2 diabetes mellitus who have moderately severe to severe nonproliferative diabetic retinopathy (NPDR) [(diabetic retinopathy severity scale (DRSS) levels 47 or 53)], confirmed by the central reading center, in whom panretinal photocoagulation (PRP) can be safely deferred for at least 6 months per the investigator
  2. Best corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score in the study eye of ≥69 letters (approximate Snellen equivalent of 20/40 or better)

Key Exclusion Criteria:

  1. Presence of diabetic macular edema (DME) threatening the center of the macula in the study eye
  2. Evidence of retinal neovascularization on clinical examination or Fluorescein Angiography (FA)
  3. Any prior focal or grid laser photocoagulation or any prior PRP in the study eye
  4. Any prior systemic anti-vascular endothelial growth factor (VEGF) treatment or intravitreal (IVT) anti-VEGF treatment in the study eye
  5. Any prior intraocular steroid injection in the study eye
  6. Current anterior segment neovascularization (ASNV), vitreous hemorrhage, or tractional retinal detachment visible at the screening assessments in the study eye

Note: Other inclusion/ exclusion criteria apply

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: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dosing regimen 1
Participants will receive IVT aflibercept dosing regimen 1
Drug: Intravitreal aflibercept injection [IAI]
Other Names:
  • BAY86-5321
  • EYLEA® (aflibercept) Injection
Experimental: Dosing regimen 2
Participants will receive IVT aflibercept dosing regimen 2
Drug: Intravitreal aflibercept injection [IAI]
Other Names:
  • BAY86-5321
  • EYLEA® (aflibercept) Injection
Sham Comparator: Dosing regimen 3
Participants will receive matching sham injections
Drug: Sham

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants Who Improved by ≥2 Steps From Baseline in the Diabetic Retinopathy Disease Severity Scale (DRSS) Score at Week 24 in the Combined 2Q16 and 2Q8 Groups
Time Frame: At Week 24
The Diabetic Retinopathy Disease Severity Scale (DRSS) may be used to describe overall retinopathy severity as well as the change in severity over time. Severity range from level 10 (DR absent) to level 85 (advanced proliferative DR: posterior fundus obscured, or center of macula detached). Here, DRSS describes severity level 47 (moderately severe NPDR) and level 53 (severe NPDR) at week 24 from baseline.
At Week 24
Percentage of Participants With a ≥ 2-step Change at Week 52 in Diabetic Retinopathy Severity Scale (DRSS) From Baseline
Time Frame: At Week 52
The Diabetic Retinopathy Disease Severity Scale (DRSS) may be used to describe overall retinopathy severity as well as the change in severity over time. Severity range from level 10 (DR absent) to level 85 (advanced proliferative DR: posterior fundus obscured, or center of macula detached). Here, DRSS describes severity level 47 (moderately severe NPDR) and level 53 (severe NPDR) at week 52 from baseline.
At Week 52

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants Who Developed a Vision-Threatening Complication Due to Diabetic Retinopathy at Week 52
Time Frame: At Week 52
Vision-threatening complications are defined as the composite outcome of proliferative diabetic retinopathy (PDR) (inclusive of participants who have vitreous hemorrhage or tractional retinal detachment believed to be due to PDR) and anterior segment neovascularization (ASNV) (participants with neovascularization of the iris [at least 2 cumulative clock hours], and/or definitive neovascularization of the iridocorneal angle).
At Week 52
Percentage of Participants Who Developed Central Involved-Diabetic Macular Edema (CI-DME) at Week 52
Time Frame: At Week 52
The percentage of participants who developed CI-DME at week 52 were reported.
At Week 52
Time to Development of Any Neovascular Vision Threatening Complication (PDR/ASNV) Through Week 52
Time Frame: Baseline through week 52 (day 365)
Vision-threatening complication (VTC) is defined as the composite outcome of proliferative diabetic retinopathy (PDR) (inclusive of participants who have vitreous hemorrhage or tractional retinal detachment believed to be due to PDR) and anterior segment neovascularization (ASNV) (participants with neovascularization of the iris [at least 2 cumulative clock hours], and/or definitive neovascularization of the iridocorneal angle). Vision Threatening Complications include PDR/ASNV identified by investigators and Diabetic Retinopathy Scale Score (DRSS) >61.
Baseline through week 52 (day 365)
Time to Development of Central Involved-Diabetic Macular Edema (CI-DME) Through Week 52
Time Frame: Baseline through week 52 (day 365)
Time to develop Central Involved-Diabetic Macular Edema (CI-DME) through week 52 reported.
Baseline through week 52 (day 365)
Percentage of Participants Who Received Panretinal Photocoagulation (PRP), Inclusive of Participants Undergoing Vitrectomy With Endolaser, at Week 52
Time Frame: At Week 52
The percentage of participants who received panretinal photocoagulation (PRP), inclusive of participants undergoing vitrectomy with endolaser, at week 52 were reported.
At Week 52
Area Under the Curve (AUC) for Change From Baseline in Best Corrected Visual Acuity (BCVA) at Week 52
Time Frame: At week 52
The area under the curve (AUC) is the area under the best corrected visual acuity (BCVA) versus time curve from baseline to week 52. Visual function of the study eye was assessed at a distance of 4 meters at every study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. BCVA scale range is 0 (worst) to 100 (best).
At week 52

Collaborators and Investigators

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

Sponsor

Regeneron Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

March 29, 2016

Primary Completion (Actual)

August 6, 2018

Study Completion (Actual)

July 16, 2019

Study Registration Dates

First Submitted

March 20, 2016

First Submitted That Met QC Criteria

March 23, 2016

First Posted (Estimate)

March 24, 2016

Study Record Updates

Last Update Posted (Actual)

July 30, 2020

Last Update Submitted That Met QC Criteria

July 15, 2020

Last Verified

July 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VGFTe-OD-1411
  • 2016-002639-14 (EudraCT Number)

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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