NCT04429503CompletedPhase 2
A Randomized, Double-Masked, Active-Controlled Phase 2/3 Study of the Efficacy and Safety of High-Dose Aflibercept in Patients With Diabetic Macular Edema
Regeneron Pharmaceuticals3 sites in 3 countries660 target enrollmentStarted: June 29, 2020Last updated:
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Regeneron Pharmaceuticals
- Enrollment
- 660
- Locations
- 3
- Primary Endpoint
- Change From Baseline in Best Corrected Visual Acuity (BCVA) (Early Treatment Diabetic Retinopathy Study [ETDRS] Letter Score) in the Study Eye at Week 48
Study Overview
Brief 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
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
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
Arms & Interventions
aflibercept Q8
Active Comparator
Administered every 8 weeks after a loading phase
Intervention: aflibercept (Drug)
High-Dose aflibercept Q12
Experimental
Administered every 12 weeks after a loading phase
Intervention: High-dose aflibercept (Drug)
High-Dose aflibercept Q16
Experimental
Administered every 16 weeks after a loading phase
Intervention: High-dose aflibercept (Drug)
Outcomes
Primary Outcomes
Change From Baseline in Best Corrected Visual Acuity (BCVA) (Early Treatment Diabetic Retinopathy Study [ETDRS] Letter Score) in the Study Eye at Week 48
Time Frame: Baseline, Week 48
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).
Secondary Outcomes
- Percentage of Participants With a ≥2 Step Improvement From Baseline in Diabetic Retinopathy Severity Scale (DRSS) Score at Week 48(Baseline, Week 48)
- Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline at Week 48(Baseline, Week 48)
- Percentage of Participants Without Fluid at Foveal Center at Week 48(At Week 48)
- Percentage of Participants Without Leakage on Fluorescein Angiography (FA) at Week 48(At Week 48)
- Change From Baseline in National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) Total Score at Week 48(Baseline, Week 48)
- Systemic Pharmacokinetics (PK) of Aflibercept as Assessed by Plasma Concentrations Through Week 48(Through Week 48)
- Percentage of Participants With BCVA ≥69 Letters at Week 48(At Week 48)
- Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye at Week 48(Baseline, Week 48)
- 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(Baseline, Week 48)
- Change From Baseline in BCVA in the Study Eye in Participants With Both Baseline and Week 48 BCVA(Baseline, Week 48)
- Assessment of Immunogenicity to Aflibercept by Measuring the Incidence of Treatment-emergent Anti-drug Antibodies (ADA) Response Through Week 96(Through Week 96)
- Change From Baseline in BCVA (Region-specific Analysis) in the Study Eye at Week 60(Baseline, Week 60)
- Number of Participants With Any TEAE Through Week 156(Through Week 156)
- Number of Participants With Any Serious TEAE Through Week 156(Through Week 156)
- Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Through Week 96(Through Week 96)
- Number of Participants With Any Serious TEAE Through Week 96(Through Week 96)
Investigators
Study Sites (3)
Loading locations...
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