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

Nonproliferative Diabetic Retinopathy Clinical Trial

— PANORAMA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02718326
• Other study ID #: VGFTe-OD-1411
• Secondary ID: 2016-002639-14
• Status: Completed
• Phase: Phase 3
• Start date: March 29, 2016
• Est. completion date: July 16, 2019

Study information

• Verified date: July 2020
• Source: Regeneron Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 402
• Est. completion date: July 16, 2019
• Est. primary completion date: August 6, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetic Retinopathy
• Nonproliferative Diabetic Retinopathy
• Retinal Diseases

Intervention

Drug:
• Intravitreal aflibercept injection [IAI]

• Sham

Locations

Country	Name	City	State
Germany	Regeneron Study Site	Leipzig	Saxony
Germany	Regeneron Study Site	Marburg	Hesse
Germany	Regeneron Study Site	Münster	North Rhine-Westphalia
Hungary	Regeneron Study Site	Budapest	Pest
Hungary	Regeneron Study Site	Budapest	Pest
Hungary	Regeneron Study Site	Debrecen	Hajdu-Bihar
Hungary	Regeneron Study Site	Szeged	Csongrad
Hungary	Regeneron Study Site	Zalaegerszeg	Zala
Japan	Regeneron Study Site	Amagasaki	Hyogo
Japan	Regeneron Study Site	Asahikawa	Hokkaido
Japan	Regeneron Study Site	Chiyoda	Tokyo
Japan	Regeneron Study Site	Kagoshima
Japan	Regeneron Study Site	Matsumoto	Nagano
Japan	Regeneron Study Site	Nagasaki
Puerto Rico	Regeneron Study Site	Arecibo
Puerto Rico	Regeneron Study Site	San Juan
United Kingdom	Regeneron Study Site	Camberley	Surrey
United Kingdom	Regeneron Study Site	London
United States	Regeneron Study Site	Abilene	Texas
United States	Regeneron Study Site	Albuquerque	New Mexico
United States	Regeneron Study Site	Altamonte Springs	Florida
United States	Regeneron Study Site	Arcadia	California
United States	Regeneron Study Site	Asheville	North Carolina
United States	Regeneron Study Site 1	Austin	Texas
United States	Regeneron Study Site 2	Austin	Texas
United States	Regeneron Study Siste	Baltimore	Maryland
United States	Regeneron Study Site	Baltimore	Maryland
United States	Regeneron Study Site	Baltimore	Maryland
United States	Regeneron Study Site	Beverly Hills	California
United States	Regeneron Study Site	Bloomfield	New Jersey
United States	Regeneron Study Site	Boston	Massachusetts
United States	Regeneron Study Site	Burlington	Vermont
United States	Regeneron Study Site	Charlotte	North Carolina
United States	Regeneron Study Site	Chattanooga	Tennessee
United States	Regeneron Study Site	Chicago	Illinois
United States	Regeneron Study Site	Colorado Springs	Colorado
United States	Regeneron Study Site	Columbus	Ohio
United States	Regeneron Study Site	Dallas	Texas
United States	Regeneron Study Site	Deerfield Beach	Florida
United States	Regeneron Study Site	Encino	California
United States	Regeneron Study Site	Fairfax	Virginia
United States	Regeneron Study Site	Florence	South Carolina
United States	Regeneron Study Site	Fort Myers	Florida
United States	Regeneron Study Site	Fullerton	California
United States	Regeneron Study Site	Germantown	Tennessee
United States	Regeneron Study Site	Golden	Colorado
United States	Regeneron Study Site	Hagerstown	Maryland
United States	Regeneron Study Site	Harlingen	Texas
United States	Regeneron Study Site	Henderson	Nevada
United States	Regeneron Study Site	Houston	Texas
United States	Regeneron Study Site	Indianapolis	Indiana
United States	Regeneron Study Site	Kingston	Pennsylvania
United States	Regeneron Study Site	La Jolla	California
United States	Regeneron Study Site	Ladson	South Carolina
United States	Regeneron Study Site	Lakeland	Florida
United States	Regeneron Study Site	Largo	Florida
United States	Regeneron Study Site	Lexington	Kentucky
United States	Regeneron Study Ssites	Marietta	Georgia
United States	Regeneron Study Site	Medford	Oregon
United States	Regeneron Study Site	Melbourne	Florida
United States	Regeneron Study Site	Miami	Florida
United States	Regeneron Study Site	Miami	Florida
United States	Regeneron Study Site	Morgantown	West Virginia
United States	Regeneron Study Site	Mountain View	California
United States	Regeneron Study Site	Nashville	Tennessee
United States	Regeneron Study Site	Nashville	Tennessee
United States	Regeneron Study Site	New Albany	Indiana
United States	Regeneron Study Site	New London	Connecticut
United States	Regeneron Study Site	Oak Forest	Illinois
United States	Regeneron Study Site	Oakland	California
United States	Regeneron Study Site	Oceanside	California
United States	Regeneron Study Site	Oklahoma City	Oklahoma
United States	Regeneron Study Site	Orlando	Florida
United States	Regeneron Study Site	Philadelphia	Pennsylvania
United States	Regeneron Study Site	Phoenix	Arizona
United States	Regeneron Study Site	Plantation	Florida
United States	Regeneron Study Site	Rapid City	South Dakota
United States	Regeneron Study Site	Sacramento	California
United States	Regeneron Study Site	Salt Lake City	Utah
United States	Regeneron Study Site	San Antonio	Texas
United States	Regeneron Study Site	Spokane	Washington
United States	Regeneron Study Site	Tallahassee	Florida
United States	Regeneron Study Site	Tampa	Florida
United States	Regeneron Study Site	The Woodlands	Texas
United States	Regeneron study Site	Tucker	Georgia
United States	Regeneron Study Site	Tucson	Arizona
United States	Regeneron Study Site	West Columbia	South Carolina
United States	Regeneron Study Site	Willow Park	Texas
United States	Regeneron Study Site	Winter Haven	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Germany,  Hungary,  Japan,  Puerto Rico,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Percentage of Participants Who Developed a Vision-Threatening Complication Due to Diabetic Retinopathy 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
Secondary	Percentage of Participants Who Developed Central Involved-Diabetic Macular Edema (CI-DME) at Week 52	The percentage of participants who developed CI-DME at week 52 were reported.	At Week 52
Secondary	Time to Development of Any Neovascular Vision Threatening Complication (PDR/ASNV) Through Week 52	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)
Secondary	Time to Development of Central Involved-Diabetic Macular Edema (CI-DME) Through Week 52	Time to develop Central Involved-Diabetic Macular Edema (CI-DME) through week 52 reported.	Baseline through week 52 (day 365)
Secondary	Percentage of Participants Who Received Panretinal Photocoagulation (PRP), Inclusive of Participants Undergoing Vitrectomy With Endolaser, 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
Secondary	Area Under the Curve (AUC) for Change From Baseline in Best Corrected Visual Acuity (BCVA) 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