Clinical trial NCT02718326: Study of the Efficacy and Safety of Intravitreal (IVT) Aflibercept for the Improvement of Moderately Severe to Severe Nonproliferative Diabetic Retinopathy (NPDR)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Nonproliferative Diabetic Retinopathy
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2016-03-24
Enrollment: 402
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: At Week 24
measure: Percentage of Participants With a ≥ 2-step Change at Week 52 in Diabetic Retinopathy Severity Scale (DRSS) From Baseline
timeFrame: At Week 52
Secondary outcomes:
measure: Percentage of Participants Who Developed a Vision-Threatening Complication Due to Diabetic Retinopathy at Week 52
timeFrame: At Week 52
measure: Percentage of Participants Who Developed Central Involved-Diabetic Macular Edema (CI-DME) at Week 52
timeFrame: At Week 52
measure: Time to Development of Any Neovascular Vision Threatening Complication (PDR/ASNV) Through Week 52
timeFrame: Baseline through week 52 (day 365)
measure: Time to Development of Central Involved-Diabetic Macular Edema (CI-DME) Through Week 52
timeFrame: Baseline through week 52 (day 365)
measure: Percentage of Participants Who Received Panretinal Photocoagulation (PRP), Inclusive of Participants Undergoing Vitrectomy With Endolaser, at Week 52
timeFrame: At Week 52
measure: Area Under the Curve (AUC) for Change From Baseline in Best Corrected Visual Acuity (BCVA) at Week 52
timeFrame: At week 52
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Regeneron Study Site
state: Arizona
city: Tucson
country: United States
facility: Regeneron Study Site
state: Arizona
city: Arcadia
country: United States
facility: Regeneron Study Site
state: California
city: Beverly Hills
country: United States
facility: Regeneron Study Site
state: California
city: Encino
country: United States
facility: Regeneron Study Site
state: California
city: Fullerton
country: United States
facility: Regeneron Study Site
state: California
city: La Jolla
country: United States
facility: Regeneron Study Site
state: California
city: Mountain View
country: United States
facility: Regeneron Study Site
state: California
city: Oakland
country: United States
facility: Regeneron Study Site
state: California
city: Oceanside
country: United States
facility: Regeneron Study Site
state: California
city: Sacramento
country: United States
facility: Regeneron Study Site
state: California
city: Colorado Springs
country: United States
facility: Regeneron Study Site
state: Colorado
city: Golden
country: United States
facility: Regeneron Study Site
state: Colorado
city: New London
country: United States
facility: Regeneron Study Site
state: Connecticut
city: Altamonte Springs
country: United States
facility: Regeneron Study Site
state: Florida
city: Deerfield Beach
country: United States
facility: Regeneron Study Site
state: Florida
city: Fort Myers
country: United States
facility: Regeneron Study Site
state: Florida
city: Lakeland
country: United States
facility: Regeneron Study Site
state: Florida
city: Largo
country: United States
facility: Regeneron Study Site
state: Florida
city: Melbourne
country: United States
facility: Regeneron Study Site
state: Florida
city: Miami
country: United States
facility: Regeneron Study Site
state: Florida
city: Miami
country: United States
facility: Regeneron Study Site
state: Florida
city: Orlando
country: United States
facility: Regeneron Study Site
state: Florida
city: Plantation
country: United States
facility: Regeneron Study Site
state: Florida
city: Tallahassee
country: United States
facility: Regeneron Study Site
state: Florida
city: Tampa
country: United States
facility: Regeneron Study Site
state: Florida
city: Winter Haven
country: United States
facility: Regeneron Study Site
state: Florida
city: Marietta
country: United States
facility: Regeneron Study Ssites
state: Georgia
city: Tucker
country: United States
facility: Regeneron study Site
state: Georgia
city: Chicago
country: United States
facility: Regeneron Study Site
state: Illinois
city: Oak Forest
country: United States
facility: Regeneron Study Site
state: Illinois
city: Indianapolis
country: United States
facility: Regeneron Study Site
state: Indiana
city: New Albany
country: United States
facility: Regeneron Study Site
state: Indiana
city: Lexington
country: United States
facility: Regeneron Study Site
state: Kentucky
city: Baltimore
country: United States
facility: Regeneron Study Site
state: Maryland
city: Baltimore
country: United States
facility: Regeneron Study Siste
state: Maryland
city: Baltimore
country: United States
facility: Regeneron Study Site
state: Maryland
city: Hagerstown
country: United States
facility: Regeneron Study Site
state: Maryland
city: Boston
country: United States
facility: Regeneron Study Site
state: Massachusetts
city: Henderson
country: United States
facility: Regeneron Study Site
state: Nevada
city: Bloomfield
country: United States
facility: Regeneron Study Site
state: New Jersey
city: Albuquerque
country: United States
facility: Regeneron Study Site
state: New Mexico
city: Asheville
country: United States
facility: Regeneron Study Site
state: North Carolina
city: Charlotte
country: United States
facility: Regeneron Study Site
state: North Carolina
city: Columbus
country: United States
facility: Regeneron Study Site
state: Ohio
city: Oklahoma City
country: United States
facility: Regeneron Study Site
state: Oklahoma
city: Medford
country: United States
facility: Regeneron Study Site
state: Oregon
city: Kingston
country: United States
facility: Regeneron Study Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Regeneron Study Site
state: Pennsylvania
city: Florence
country: United States
facility: Regeneron Study Site
state: South Carolina
city: Ladson
country: United States
facility: Regeneron Study Site
state: South Carolina
city: West Columbia
country: United States
facility: Regeneron Study Site
state: South Carolina
city: Rapid City
country: United States
facility: Regeneron Study Site
state: South Dakota
city: Chattanooga
country: United States
facility: Regeneron Study Site
state: Tennessee
city: Germantown
country: United States
facility: Regeneron Study Site
state: Tennessee
city: Nashville
country: United States
facility: Regeneron Study Site
state: Tennessee
city: Nashville
country: United States
facility: Regeneron Study Site
state: Tennessee
city: Abilene
country: United States
facility: Regeneron Study Site
state: Texas
city: Austin
country: United States
facility: Regeneron Study Site 1
state: Texas
city: Austin
country: United States
facility: Regeneron Study Site 2
state: Texas
city: Dallas
country: United States
facility: Regeneron Study Site
state: Texas
city: Harlingen
country: United States
facility: Regeneron Study Site
state: Texas
city: Houston
country: United States
facility: Regeneron Study Site
state: Texas
city: San Antonio
country: United States
facility: Regeneron Study Site
state: Texas
city: The Woodlands
country: United States
facility: Regeneron Study Site
state: Texas
city: Willow Park
country: United States
facility: Regeneron Study Site
state: Texas
city: Salt Lake City
country: United States
facility: Regeneron Study Site
state: Utah
city: Burlington
country: United States
facility: Regeneron Study Site
state: Vermont
city: Fairfax
country: United States
facility: Regeneron Study Site
state: Virginia
city: Spokane
country: United States
facility: Regeneron Study Site
state: Washington
city: Morgantown
country: United States
facility: Regeneron Study Site
state: West Virginia
city: Marburg
country: Germany
facility: Regeneron Study Site
state: Hesse
city: Münster
country: Germany
facility: Regeneron Study Site
state: North Rhine-Westphalia
city: Leipzig
country: Germany
facility: Regeneron Study Site
state: Saxony
city: Szeged
country: Hungary
facility: Regeneron Study Site
state: Csongrad
city: Debrecen
country: Hungary
facility: Regeneron Study Site
state: Hajdu-Bihar
city: Budapest
country: Hungary
facility: Regeneron Study Site
state: Pest
city: Budapest
country: Hungary
facility: Regeneron Study Site
state: Pest
city: Zalaegerszeg
country: Hungary
facility: Regeneron Study Site
state: Zala
city: Asahikawa
country: Japan
facility: Regeneron Study Site
state: Hokkaido
city: Amagasaki
country: Japan
facility: Regeneron Study Site
state: Hyogo
city: Matsumoto
country: Japan
facility: Regeneron Study Site
state: Nagano
city: Chiyoda
country: Japan
facility: Regeneron Study Site
state: Tokyo
city: Kagoshima
country: Japan
facility: Regeneron Study Site
city: Nagasaki
country: Japan
facility: Regeneron Study Site
city: Arecibo
country: Puerto Rico
facility: Regeneron Study Site
city: San Juan
country: Puerto Rico
facility: Regeneron Study Site
city: Camberley
country: United Kingdom
facility: Regeneron Study Site
state: Surrey
city: London
country: United Kingdom
facility: Regeneron Study Site
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References:
citation: 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.