Phase 3 N=660 Randomized Quadruple-blind Treatment

Study of a High-Dose Aflibercept in Participants With Diabetic Eye Disease

Diabetic Macular Edema · Type 1 Diabetes Mellitus · Type 2 Diabetes Mellitus

Bottom Line

View on ClinicalTrials.gov: NCT04429503 ↗

Enrolled (actual)

660

Serious AEs

29.4%

Results posted

Nov 2023

Primary outcome: Primary: Change From Baseline in Best Corrected Visual Acuity (BCVA) (Early Treatment Diabetic Retinopathy Study [ETDRS] Letter Score) in the Study Eye at Week 48 — 8.67; 8.10; 7.23 Letters — p=<0.0001

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: aflibercept (Drug); High-dose aflibercept (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Regeneron Pharmaceuticals
Primary completion: May 2022

Outcome Measures

Outcome	Result	p-value
PRIMARY Change From Baseline in Best Corrected Visual Acuity (BCVA) (Early Treatment Diabetic Retinopathy Study [ETDRS] Letter Score) in the Study Eye at Week 48	8.67; 8.10; 7.23	<0.0001 sig
SECONDARY Percentage of Participants With a ≥2 Step Improvement From Baseline in Diabetic Retinopathy Severity Scale (DRSS) Score at Week 48	26.6; 29.0; 19.6	—
SECONDARY Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline at Week 48	23.0; 18.7; 16.6	—
SECONDARY Percentage of Participants With BCVA ≥69 Letters at Week 48	63.0; 65.3; 62.6	—
SECONDARY Percentage of Participants Without Fluid at Foveal Center at Week 48	54.5; 58.5; 43.8	—
SECONDARY Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye at Week 48	-164.85; -176.77; -148.84	—
SECONDARY Percentage of Participants Without Leakage on Fluorescein Angiography (FA) at Week 48	2.5; 7.6; 0.7	—
SECONDARY Change From Baseline in National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) Total Score at Week 48	2.82; 4.06; 2.94	—
SECONDARY Systemic Pharmacokinetics (PK) of Aflibercept as Assessed by Plasma Concentrations Through Week 48	0.00102; 0.0111; 0.00105	—
SECONDARY Change From Baseline in BCVA in the Study Eye in Participants With Both Baseline and Week 48 BCVA	9.11; 9.14; 9.11	—
SECONDARY Change From 8-weeks Post Initial Treatment Phase in BCVA in the Study Eye in Participants With Both 8-weeks Post Initial Treatment Phase BCVA and Week 48 BCVA	1.63; 1.68; 1.64	—
SECONDARY Change From Baseline in BCVA (Region-specific Analysis) in the Study Eye at Week 60	9.40; 8.52; 7.64	—
SECONDARY Assessment of Immunogenicity to Aflibercept by Measuring the Incidence of Treatment-emergent Anti-drug Antibodies (ADA) Response Through Week 96	4; 11; 2; 2; 7; 4	—
SECONDARY Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Through Week 96	134; 277; 143	—
SECONDARY Number of Participants With Any Serious TEAE Through Week 96	46; 81; 44	—
SECONDARY Number of Participants With Any TEAE Through Week 156	64; 122; 59	—
SECONDARY Number of Participants With Any Serious TEAE Through Week 156	27; 41; 22	—

Summary

The primary objective of the study is to determine if treatment with high-dose aflibercept (HD) at intervals of 12 or 16 weeks provides non-inferior best corrected visual acuity (BCVA) compared to aflibercept dosed every 8 weeks. The secondary objectives of the study are as follows: * To determine the effect of HD vs. aflibercept on anatomic and other visual measures of response * To evaluate the safety, immunogenicity, and pharmacokinetics (PK) of aflibercept

Eligibility Criteria

Key Inclusion Criteria

Diabetic macular edema (DME) with central involvement in the study eye
Best corrected visual acuity (BCVA) early treatment diabetic retinopathy study (ETDRS) letter score of 78 to 24 (approximate Snellen equivalent of 20/32 to 20/320) in the study eye with decreased vision determined to be primarily the result of DME
Willing and able to comply with clinic visits and study-related procedures
Provide informed consent signed by study participant or legally acceptable representative

Extension Phase: All randomized patients that complete visit 26, week 96, as long as the patient 1) provides informed consent and 2) no treatment for DME has been given in the study eye other than the randomized study treatment.

Key Exclusion Criteria

Evidence of macular edema due to any cause other than diabetes mellitus in either eye
Active proliferative diabetic retinopathy in the study eye
IVT anti-VEGF treatment (aflibercept, ranibizumab, bevacizumab, brolucizumab, pegaptanib sodium) or panretinal laser photocoagulation (PRP) /macular laser photocoagulation within 12 weeks (84 days) or intraocular or periocular corticosteroids within 16 weeks (112 days) of the screening visit in the study eye
Prior IVT investigational agents in either eye (eg, anti-ang-2/anti-VEGF bispecific monoclonal antibodies, gene therapy, etc.) at any time
Treatment with ocriplasmin (JETREA®) in the study eye at any time

NOTE: Other Protocol Defined Inclusion/Exclusion Criteria Apply

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT04429503). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.