Study of a High-Dose Aflibercept in Participants With Diabetic Eye Disease
- Conditions
- Type 1 Diabetes MellitusDiabetic Macular EdemaType 2 Diabetes Mellitus
- Interventions
- Drug: High-dose aflibercept
- Registration Number
- NCT04429503
- Lead Sponsor
- Regeneron Pharmaceuticals
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 660
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description High-Dose aflibercept Q16 High-dose aflibercept Administered every 16 weeks after a loading phase High-Dose aflibercept Q12 High-dose aflibercept Administered every 12 weeks after a loading phase aflibercept Q8 aflibercept Administered every 8 weeks after a loading phase
- Primary Outcome Measures
Name Time Method Change From Baseline in Best Corrected Visual Acuity (BCVA) (Early Treatment Diabetic Retinopathy Study [ETDRS] Letter Score) in the Study Eye at Week 48 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 Outcome Measures
Name Time Method Percentage of Participants With BCVA ≥69 Letters at Week 48 At 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).
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline at Week 48 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). Only one study eye per participant was analyzed within the study
Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye at Week 48 Baseline, Week 48 Central Retinal Thickness (CRT) was measured in the study eye by spectral domain optical coherence tomography (SD-OCT).
Percentage of Participants Without Leakage on Fluorescein Angiography (FA) at Week 48 At Week 48 Leakage is the release of fluorescein dye from diseased retinal vessels.
Percentage of Participants Without Fluid at Foveal Center at Week 48 At Week 48 Retinal fluid status was evaluated using spectral domain optical coherence tomography (SD-OCT) on the study eye.
Percentage of Participants With a ≥2 Step Improvement From Baseline in Diabetic Retinopathy Severity Scale (DRSS) Score at Week 48 Baseline, Week 48 The DRSS was assessed according to the following scale: 10 = Diabetic retinopathy (DR) absent, 14 = DR questionable, 15 = DR questionable, 20 = Micro-aneurysms only, 35 = Mild Non-proliferative diabetic retinopathy (NPDR), 43 = Moderate NPDR, 47 = Moderately severe NPDR, 53 = Severe NPDR, 61 = Mild Proliferative diabetic retinopathy (PDR), 65 = Moderate PDR, 71 = High-risk PDR, 75 = High-risk PDR, 81 = Advanced PDR: fundus partially obscured, center of macula attached, 85 = Advanced PDR: posterior fundus obscured, or center of macula detached, 90 = cannot grade, even sufficiently for level 81 or 85.
Change From Baseline in National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) Total Score at Week 48 Baseline, Week 48 Vision-specific quality of life is assessed with the NEI VFQ-25 (National Eye Institute Visual Function Questionnaire), i.e. a 25-item questionnaire that gives a score on a scale from 0 (worst) to 100 (best = no vision problems).
Change From Baseline in BCVA (Region-specific Analysis) in the Study Eye at Week 60 Baseline, Week 60 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).
Systemic Pharmacokinetics (PK) of Aflibercept as Assessed by Plasma Concentrations Through Week 48 Through Week 48 Concentrations of Free Aflibercept in Plasma by Time and Treatment Group
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 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). (Per SAP Version 2.0 Appendix 10.9 for US Only)
Change From Baseline in BCVA in the Study Eye in Participants With Both Baseline and Week 48 BCVA 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). (Per Statistical Analysis Plan (SAP) Version 2.0 Appendix 10.9 for US Only)
Number of Participants With Any Serious TEAE Through Week 96 Through Week 96 A TEAE is an AE starting after the first dose of study drug to the last dose of study drug (active or sham) plus 30 days. Additionally, for patients who are still participating in the study (ie, have not been withdrawn and are continuing in the extension phase of the study) as of the week 96 visit all AEs up through the date of the week 96 visit were considered treatment-emergent.
Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Through Week 96 Through Week 96 A TEAE is an AE starting after the first dose of study drug to the last dose of study drug (active or sham) plus 30 days. Additionally, for patients who are still participating in the study (ie, have not been withdrawn and are continuing in the extension phase of the study) as of the week 96 visit all AEs up through the date of the week 96 visit were considered treatment-emergent.
Assessment of Immunogenicity to Aflibercept by Measuring the Incidence of Treatment-emergent Anti-drug Antibodies (ADA) Response Through Week 96 Through Week 96 Number of participants with pre-existing immunoreactivity and treatment-emergent ADA response reported
Trial Locations
- Locations (3)
Regeneron Study Site 1
🇭🇺Pecs, Baranya, Hungary
Regeneron Study Site
🇬🇧London, United Kingdom
Regeneron Study Site 2
🇺🇸San Antonio, Texas, United States