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NCT02718326: PANORAMA

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

Completed Phase 3 Results posted Last updated 30 July 2020
What this trial tests

Phase 3 trial testing Intravitreal aflibercept injection [IAI] in Nonproliferative Diabetic Retinopathy in 402 participants. Completed in 16 July 2019.

Timeline
29 March 2016
Primary endpoint
6 August 2018
16 July 2019

Quick facts

Lead sponsorRegeneron Pharmaceuticals
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment402
Start date29 March 2016
Primary completion6 August 2018
Estimated completion16 July 2019
Sites89 locations across Japan, United Kingdom, Germany, Hungary, Puerto Rico, United States

Drugs / interventions tested

Conditions studied

Sponsor

Regeneron Pharmaceuticals — full company profile →

Who can join

18 and older, any sex, with Nonproliferative Diabetic Retinopathy. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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 Primary · 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.

GroupValue95% CI
Sham Treatment6.0
Intravitreal Aflibercept Injection (IAI) 2Q1661.5
Intravitreal Aflibercept Injection (IAI) 2Q855.2
IAI 2 mg Groups Combined (2Q16 & 2Q8)58.4
Percentage of Participants With a ≥ 2-step Change at Week 52 in Diabetic Retinopathy Severity Scale (DRSS) From Baseline Primary · 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.

GroupValue95% CI
Sham Treatment15.0
Intravitreal Aflibercept Injection (IAI) 2Q1665.2
Intravitreal Aflibercept Injection (IAI) 2Q879.9
Percentage of Participants Who Developed a Vision-Threatening Complication Due to Diabetic Retinopathy at Week 52 Secondary · 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).

GroupValue95% CI
Sham Treatment20.3
Intravitreal Aflibercept Injection (IAI) 2Q163.7
Intravitreal Aflibercept Injection (IAI) 2Q83.0
Percentage of Participants Who Developed Central Involved-Diabetic Macular Edema (CI-DME) at Week 52 Secondary · At Week 52

The percentage of participants who developed CI-DME at week 52 were reported.

GroupValue95% CI
Sham Treatment25.6
Intravitreal Aflibercept Injection (IAI) 2Q166.7
Intravitreal Aflibercept Injection (IAI) 2Q88.2
Time to Development of Any Neovascular Vision Threatening Complication (PDR/ASNV) Through Week 52 Secondary · 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.

GroupValue95% CI
Sham TreatmentNA371 – NA
Intravitreal Aflibercept Injection (IAI) 2Q16NANA – NA
Intravitreal Aflibercept Injection (IAI) 2Q8NANA – NA
Time to Development of Central Involved-Diabetic Macular Edema (CI-DME) Through Week 52 Secondary · Baseline through week 52 (day 365)

Time to develop Central Involved-Diabetic Macular Edema (CI-DME) through week 52 reported.

GroupValue95% CI
Sham TreatmentNA333 – NA
Intravitreal Aflibercept Injection (IAI) 2Q16NANA – NA
Intravitreal Aflibercept Injection (IAI) 2Q8NANA – NA
Percentage of Participants Who Received Panretinal Photocoagulation (PRP), Inclusive of Participants Undergoing Vitrectomy With Endolaser, at Week 52 Secondary · At Week 52

The percentage of participants who received panretinal photocoagulation (PRP), inclusive of participants undergoing vitrectomy with endolaser, at week 52 were reported.

GroupValue95% CI
Sham Treatment6.8
Intravitreal Aflibercept Injection (IAI) 2Q160.7
Intravitreal Aflibercept Injection (IAI) 2Q80.7
Area Under the Curve (AUC) for Change From Baseline in Best Corrected Visual Acuity (BCVA) at Week 52 Secondary · 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).

GroupValue95% CI
Sham Treatment0.5± 3.01
Intravitreal Aflibercept Injection (IAI) 2Q161.7± 3.50
Intravitreal Aflibercept Injection (IAI) 2Q81.3± 3.49

Adverse events — posted to ClinicalTrials.gov

Time frame: All Adverse Events (AEs) were collected from signature of the informed consent form up to week 100 regardless of seriousness or relationship to investigational product. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Sham Treatment
Serious: 38/133 (29%)
Deaths: 8/133
Intravitreal Aflibercept Injection (IAI) 2Q16
Serious: 38/135 (28%)
Deaths: 1/135
Intravitreal Aflibercept Injection (IAI) 2Q8
Serious: 47/134 (35%)
Deaths: 3/134
IAI 2 mg Groups Combined (2Q16 & 2Q8)
Serious: 85/269 (32%)
Deaths: 4/269

Serious adverse events (136 terms)

ReactionSystemSham TreatmentIntravitreal Aflibercept I…Intravitreal Aflibercept I…IAI 2 mg Groups Combined (…
Coronary artery diseaseCardiac disorders
CellulitisInfections and infestations
PneumoniaInfections and infestations
Cardiac failure congestiveCardiac disorders
OsteomyelitisInfections and infestations
Acute kidney injuryRenal and urinary disorders
Cerebrovascular accidentNervous system disorders
Myocardial infarctionCardiac disorders
Diabetic foot infectionInfections and infestations
SepsisInfections and infestations
DehydrationMetabolism and nutrition disorders
Ischaemic strokeNervous system disorders
Diabetic footSkin and subcutaneous tissue disorders
Visual acuity reduced Fellow EyeEye disorders
Acute myocardial infarctionCardiac disorders
Cardiac failure acuteCardiac disorders
Coronary artery stenosisCardiac disorders
Left ventricular failureCardiac disorders
Abscess limbInfections and infestations
Diabetic ketoacidosisMetabolism and nutrition disorders
HypoglycaemiaMetabolism and nutrition disorders
Acute respiratory failureRespiratory, thoracic and mediastinal disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
Pulmonary hypertensionRespiratory, thoracic and mediastinal disorders
AnaemiaBlood and lymphatic system disorders
Other adverse events (30 terms — click to expand)

ReactionSystemSham TreatmentIntravitreal Aflibercept I…Intravitreal Aflibercept I…IAI 2 mg Groups Combined (…
HypertensionVascular disorders
Conjunctival haemorrhage Study EyeEye disorders
Diabetic retinal oedema Study EyeEye disorders
Diabetic retinal oedema Fellow EyeEye disorders
Urinary tract infectionInfections and infestations
Diabetic retinopathy Fellow EyeEye disorders
NasopharyngitisInfections and infestations
Diabetic retinopathy Study EyeEye disorders
Vitreous floaters Study EyeEye disorders
Diabetes mellitusMetabolism and nutrition disorders
Glycosylated haemoglobin increasedInvestigations
Cataract Study EyeEye disorders
Eye pain Study EyeEye disorders
HeadacheNervous system disorders
BronchitisInfections and infestations
InfluenzaInfections and infestations
Retinal exudates Study EyeEye disorders
Vitreous detachment Study EyeEye disorders
FallInjury, poisoning and procedural complications
Cataract Fellow EyeEye disorders
Conjunctival haemorrhage Fellow EyeEye disorders
Macular oedema Fellow EyeEye disorders
ConstipationGastrointestinal disorders
CellulitisInfections and infestations
NauseaGastrointestinal disorders
Vitreous haemorrhage Fellow EyeEye disorders
Blood glucose increasedInvestigations
Blepharitis Fellow EyeEye disorders
Blepharitis Study EyeEye disorders
Retinal exudates Fellow EyeEye disorders

Most-reported serious reactions: Coronary artery disease, Cellulitis, Pneumonia, Cardiac failure congestive, Osteomyelitis, Acute kidney injury, Cerebrovascular accident, Myocardial infarction.

Data from ClinicalTrials.gov NCT02718326 adverse events section.

Sponsor's own description

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

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. The role of inflammation in immune system of diabetic retinopathy: Molecular mechanisms, pathogenetic role and therapeutic implications.
    Yue T, Shi Y, Luo S, Weng J, et al · · 2022 · cited 120× · PMID 36582230 · DOI 10.3389/fimmu.2022.1055087
  2. The role of anti-vascular endothelial growth factor (anti-VEGF) in the management of proliferative diabetic retinopathy.
    Zhao Y, Singh RP. · · 2018 · cited 120× · PMID 30181760 · DOI 10.7573/dic.212532
  3. Evaluation of Intravitreal Aflibercept for the Treatment of Severe Nonproliferative Diabetic Retinopathy: Results From the PANORAMA Randomized Clinical Trial.
    Brown DM, Wykoff CC, Boyer D, Heier JS, et al · · 2021 · cited 111× · PMID 34351414 · DOI 10.1001/jamaophthalmol.2021.2809
  4. Efficacy and safety of intravitreal anti-VEGF therapy in diabetic retinopathy: what we have learned and what should we learn further?
    Uludag G, Hassan M, Matsumiya W, Pham BH, et al · · 2022 · cited 60× · PMID 35818801 · DOI 10.1080/14712598.2022.2100694
  5. Vascular endothelial growth factor inhibition and proliferative diabetic retinopathy, a changing treatment paradigm?
    Wu L, Acón D, Wu A, Wu M. · · 2019 · cited 12× · PMID 31942426 · DOI 10.4103/tjo.tjo_67_19
  6. Dopamine metabolite levels in the vitreous of diabetic and non-diabetic humans.
    Hendrick A, Smith J, Stelton C, Barb S, et al · · 2020 · cited 5× · PMID 32360553 · DOI 10.1016/j.exer.2020.108040
  7. Proliferative Diabetic Retinopathy Events in Patients With Diabetic Macular Edema: Post Hoc Analysis of VISTA and VIVID Trials.
    Do DV, Gordon C, Suñer IJ, Reed K, et al · · 2022 · cited 2× · PMID 37007930 · DOI 10.1177/24741264221093914
  8. Effect of intravitreal VEGF inhibitors on renal-related adverse events in patients with diabetes mellitus: systematic review and meta-analysis.
    Zheng Y, Zhang F, Li X, Zhang X, et al · · 2025 · PMID 41322292 · DOI 10.3389/fphar.2025.1691597

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