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

NCT02718326 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: VGFTe-OD-14112016-002639-14
• Study Type: interventional
• Target: 402
• Locations: 6 countries
• Sites: 89

Brief Summary

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

Conditions

Nonproliferative Diabetic Retinopathy

Outcome Measures

Primary Outcomes (2)

• 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

  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

  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 Outcomes (6)

• Percentage of Participants Who Developed a Vision-Threatening Complication Due to Diabetic Retinopathy at Week 52

  At Week 52

• Percentage of Participants Who Developed Central Involved-Diabetic Macular Edema (CI-DME) at Week 52

  At Week 52

• Time to Development of Any Neovascular Vision Threatening Complication (PDR/ASNV) Through Week 52

  Baseline through week 52 (day 365)

• Time to Development of Central Involved-Diabetic Macular Edema (CI-DME) Through Week 52

  Baseline through week 52 (day 365)

• Percentage of Participants Who Received Panretinal Photocoagulation (PRP), Inclusive of Participants Undergoing Vitrectomy With Endolaser, at Week 52

  At Week 52

Study Arms (3)

Dosing regimen 1

EXPERIMENTAL

Participants will receive IVT aflibercept dosing regimen 1

Drug: Intravitreal aflibercept injection [IAI]

Dosing regimen 2

EXPERIMENTAL

Participants will receive IVT aflibercept dosing regimen 2

Drug: Intravitreal aflibercept injection [IAI]

Dosing regimen 3

SHAM COMPARATOR

Participants will receive matching sham injections

Drug: Sham

Interventions

Intravitreal aflibercept injection [IAI] DRUG

Also known as: EYLEA® (aflibercept) Injection, BAY86-5321

Dosing regimen 1; Dosing regimen 2

Sham DRUG

Dosing regimen 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)

You may not qualify if:

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

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

Study Sites (89)

Regeneron Study Site

Phoenix, Arizona, 85020, United States

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Tucson, Arizona, 85704, United States

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Arcadia, California, 91007, United States

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Beverly Hills, California, 90211, United States

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Encino, California, 91436, United States

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Fullerton, California, 92835, United States

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La Jolla, California, 92093, United States

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Mountain View, California, 94040, United States

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Oakland, California, 94609, United States

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Oceanside, California, 92056, United States

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Sacramento, California, 95841, United States

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Colorado Springs, Colorado, 80909, United States

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Golden, Colorado, 80401, United States

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New London, Connecticut, 06320, United States

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Altamonte Springs, Florida, 32701, United States

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Deerfield Beach, Florida, 33064, United States

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Fort Myers, Florida, 33912, United States

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Lakeland, Florida, 33805, United States

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Largo, Florida, 33770, United States

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Melbourne, Florida, 32901, United States

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Miami, Florida, 33126, United States

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Miami, Florida, 33143, United States

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Orlando, Florida, 32806, United States

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Plantation, Florida, 33324, United States

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Tallahassee, Florida, 32308, United States

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Tampa, Florida, 33612, United States

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Winter Haven, Florida, 33880, United States

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Marietta, Georgia, 30060, United States

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Tucker, Georgia, 30084, United States

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Chicago, Illinois, 60612, United States

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Oak Forest, Illinois, 60452, United States

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Indianapolis, Indiana, 46290, United States

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New Albany, Indiana, 47150, United States

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Lexington, Kentucky, 40509, United States

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Baltimore, Maryland, 21204, United States

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Baltimore, Maryland, 21209, United States

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Baltimore, Maryland, 21287, United States

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Hagerstown, Maryland, 21740, United States

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Boston, Massachusetts, 02114, United States

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Henderson, Nevada, 89052, United States

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Bloomfield, New Jersey, 07003, United States

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Albuquerque, New Mexico, 87109, United States

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Asheville, North Carolina, 28803, United States

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Charlotte, North Carolina, 28210, United States

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Columbus, Ohio, 43212, United States

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Oklahoma City, Oklahoma, 73104, United States

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Medford, Oregon, 97504, United States

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Kingston, Pennsylvania, 18704, United States

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Philadelphia, Pennsylvania, 19107, United States

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Florence, South Carolina, 29501, United States

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Ladson, South Carolina, 29456, United States

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West Columbia, South Carolina, 29169, United States

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Rapid City, South Dakota, 57701, United States

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Chattanooga, Tennessee, 37421, United States

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Germantown, Tennessee, 38138, United States

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Nashville, Tennessee, 37203, United States

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Nashville, Tennessee, 37232, United States

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Abilene, Texas, 79606, United States

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Austin, Texas, 78705, United States

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Austin, Texas, 78705, United States

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Dallas, Texas, 75231, United States

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Harlingen, Texas, 78559, United States

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Houston, Texas, 77030, United States

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San Antonio, Texas, 78240, United States

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The Woodlands, Texas, 77384, United States

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Willow Park, Texas, 76087, United States

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Salt Lake City, Utah, 84132, United States

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Burlington, Vermont, 05401, United States

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Fairfax, Virginia, 22031, United States

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Spokane, Washington, 99204, United States

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Morgantown, West Virginia, 26506, United States

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Marburg, Hesse, 35043, Germany

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Münster, North Rhine-Westphalia, 48145, Germany

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Leipzig, Saxony, 04103, Germany

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Szeged, Csongrád megye, 6720, Hungary

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Debrecen, Hajdú-Bihar, 4032, Hungary

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Budapest, Pest County, 1062, Hungary

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Budapest, Pest County, 1106, Hungary

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Zalaegerszeg, Zala County, 8900, Hungary

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Asahikawa, Hokkaido, 078-8510, Japan

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Amagasaki, Hyōgo, 660-8550, Japan

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Matsumoto, Nagano, 390-8621, Japan

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Chiyoda City, Tokyo, 101-8309, Japan

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Kagoshima, 890-8520, Japan

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Nagasaki, 852-8501, Japan

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Arecibo, 00613, Puerto Rico

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San Juan, 00907, Puerto Rico

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Camberley, Surrey, GU16 7UJ, United Kingdom

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London, EC1V 2PD, United Kingdom

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Related Publications (1)

• Brown DM, Wykoff CC, Boyer D, Heier JS, Clark WL, Emanuelli A, Higgins PM, Singer M, Weinreich DM, Yancopoulos GD, Berliner AJ, Chu K, Reed K, Cheng Y, Vitti R. Evaluation of Intravitreal Aflibercept for the Treatment of Severe Nonproliferative Diabetic Retinopathy: Results From the PANORAMA Randomized Clinical Trial. JAMA Ophthalmol. 2021 Sep 1;139(9):946-955. doi: 10.1001/jamaophthalmol.2021.2809.

  PMID: 34351414 DERIVED

MeSH Terms

Interventions

aflibercept; Injections; salicylhydroxamic acid

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Results Point of Contact

• Title: Clinical Trial Management
• Organization: Regeneron Pharmaceuticals, Inc.

clinicaltrials@regeneron.com

844-734-6643

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2016
• First Posted: March 24, 2016
• Study Start: March 29, 2016
• Primary Completion: August 6, 2018
• Study Completion: July 16, 2019
• Last Updated: July 30, 2020
• Results First Posted: November 21, 2019

Record last verified: 2020-07

Locations

PR (2); US (71); JP (6); DE (3); GB (2); HU (5)