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

Phase 3

Completed

• Conditions: Nonproliferative Diabetic Retinopathy
• Interventions: Drug: Sham; Drug: Intravitreal aflibercept injection [IAI]

• Registration Number: NCT02718326
• Lead Sponsor: Regeneron Pharmaceuticals

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-03-20
• Study First Submitted QC: 2016-03-23
• Study First Posted: 2016-03-24
• Study Start: 2016-03-29
• Primary Completion: 2018-08-06
• Study Completion: 2019-07-16
• Results First Submitted: 2019-08-06
• Results First Submitted QC: 2019-11-19
• Results First Posted: 2019-11-21
• Status Verified: 2020-07
• Last Update Submitted: 2020-07-15
• Last Update Posted: 2020-07-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 402

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dosing regimen 3	Sham	Participants will receive matching sham injections
Dosing regimen 2	Intravitreal aflibercept injection [IAI]	Participants will receive IVT aflibercept dosing regimen 2
Dosing regimen 1	Intravitreal aflibercept injection [IAI]	Participants will receive IVT aflibercept dosing regimen 1

Primary Outcome Measures

Name	Time	Method
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	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.
Percentage of Participants With a ≥ 2-step Change at Week 52 in Diabetic Retinopathy Severity Scale (DRSS) From Baseline	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.

Secondary Outcome Measures

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

Trial Locations

Locations (6)

Regeneron study Site; 🇺🇸 Tucker, Georgia, United States

Regeneron Study Site; 🇬🇧 London, United Kingdom

Regeneron Study Ssites; 🇺🇸 Marietta, Georgia, United States

Regeneron Study Siste; 🇺🇸 Baltimore, Maryland, United States

Regeneron Study Site 1; 🇺🇸 Austin, Texas, United States

Regeneron Study Site 2; 🇺🇸 Austin, Texas, United States