Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
aflibercept · 14 trials · 12 indications
The primary endpoint is the change from baseline in BCVA at Week 48. Efficacy analyses will be conducted using the Full analysis set (FAS). The primary efficacy analysis will be a comparison between 2 comparative arms: HDq16 vs. 2q8. The primary efficacy variable (Change from baseline in BCVA by ETDRS letter score at Week 48) will be analyzed using FAS with an Mixed Model for Repeated Measurements (MMRM) analysis model. The model includes baseline BCVA as a covariate, treatment group, baseline CST category, baseline BCVA category, prior DME treatment, and visit as fixed effects, and interaction terms for treatment by visit and baseline BCVA by visit. A Kenward-Roger approximation will be used for the denominator degrees of freedom.
Active ROP was ROP requiring treatment and unfavorable structural outcome was defined as retinal detachment, macular dragging, macular fold, or retrolental opacity. For participants with both eyes enrolled in the study, both eyes must have met the endpoint. Participants with only one study eye enrolled were responders if the respective eye responded.
The primary efficacy analysis was on the changes in IOP from baseline to Week 1 (LOCF).
It compared the change in IOP from baseline to pre-dose at Week 1 between the aflibercept group vs the sham group.
Visual function of the study eye was assessed using the ETDRS protocol, which is a widely accepted international standard for macular laser photocoagulation treatment. A higher score represents better functioning. LOCF censored measurements after additional treatment.
Visual function of the study eye was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better functioning.
Assess the safety of 2 mg intravitreal aflibercept injections (IAI) to achieve and maintain DRSS improvements (2 or more steps) in patients with a baseline DRSS level of 47A to 71A inclusive as determined by reading center determined DRSS gradings on OPTOS fundus photos and leakage index on OPTOS WF-FA
• Assess the safety and tolerability of IAI for the treatment of proliferative diabetic retinopathy by evaluating the incidence and severity of ocular and systemic adverse events through week 52 and week 100.
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).
Center subfield=the circular area in 1 millimeter (mm) diameter centered around the center point of the fovea. Without fluid defined as absence of intraretinal fluid (IRF) and/or subretinal fluid (SRF) in the center subfield. Presence of retinal fluid was assessed by spectral domain optical coherence tomography (SD-OCT)
CR/LT measured in micrometers (µm); lower individual values represent better outcomes.
The primary endpoint in the study consists of intraocular aflibercept (free and bound) concentrations following intravitreal aflibercept injection.
Number of participants with ocular and non-ocular adverse events (AEs) in both treatment arms.
| Arm | Type | Description |
|---|---|---|
| Aflibercept 8 mg | EXPERIMENTAL | Participants previously treated with anti-vascular endothelial growth factor (anti-VEGF) medications |
| 2 mg aflibercept | ACTIVE_COMPARATOR | Participants that will be enrolled to this treatment arm will receive 2 mg aflibercept every 8 weeks following 5 initial monthly doses starting at Baseline (visit 2) (2q8) for the chosen "study eye". Randomization will be stratified according to baseline Central subfield thickness (CST) (\<400 µm, ≥400 µm), baseline Best corrected visual acuity (BCVA) (\<60 vs. ≥60 ETDRS letters) and prior treatment for DME. |
| 8 mg aflibercept (high dose) | EXPERIMENTAL | Participants that will be enrolled to this treatment arm will receive 8 mg (high dose - HD) aflibercept every 16 weeks following 3 initial monthly doses, starting at Baseline (Visit 2) (HDq16) for the chosen "study eye". Randomization will be stratified according to baseline Central subfield thickness (CST) (\<400 µm, ≥400 µm), baseline Best corrected visual acuity (BCVA) (\<60 vs. ≥60 ETDRS letters) and prior treatment for DME. |
| Aflibercept Group | EXPERIMENTAL | Patients will receive a single intravitreal (IVT) injection per eligible eye at baseline. |
| Laser Group | EXPERIMENTAL | Patients will undergo laser treatment in each eligible eye at baseline. |
| NVG patients | EXPERIMENTAL | Japanese patients with neovascular glaucoma |
| Aflibercept | EXPERIMENTAL | Aflibercept 2 mg Intravitreal (IVT) injection group |
| Sham Injection | SHAM_COMPARATOR | Sham injection group |
| Intravitreal Aflibercept Injection 2Q4 | EXPERIMENTAL | Participants received 2 mg Intravitreal aflibercept injection (IAI) (Eylea, VEGF \[vascular endothelial growth factor\] Trap-Eye, BAY86-5321) every 4 weeks (2Q4) over 48 weeks. |
| Intravitreal Aflibercept Injection 2Q8 | EXPERIMENTAL | Participants received 2 mg Intravitreal aflibercept injection (IAI) (Eylea, VEGF Trap-Eye, BAY86-5321) every 4 weeks until Week 16 and every 8 weeks (2Q8) thereafter, over 48 weeks. |
| Macular Laser Photocoagulation | ACTIVE_COMPARATOR | Participants received laser treatment at baseline and as needed at visits at which laser retreatment criteria were met, but no more frequently than every 12 weeks over 48 weeks. |
| Aflibercept injection (EYLEA, VEGF Trap-Eye, BAY86-5321) | EXPERIMENTAL | Participants received 2.0 mg intravitreal aflibercept injection (IAI) every 4 weeks for the first 12 weeks, followed by additional 2.0 mg IAI every 8 weeks until week 48. Additionally, sham photodynamic therapy (PDT) treatments was administered as needed. |
| PDT treatments | ACTIVE_COMPARATOR | Participants received PDT as needed. Additionally, sham IAI injections was administered until week 28. Thereafter, participants received active IAI treatment until week 48. |
| Group 1 | EXPERIMENTAL | Treatment based on central reading center reading evaluation of DRSS (diabetic retinopathy severity scale) level based on OPTOS funds photos. |
| Group 2 | EXPERIMENTAL | Treatment based on central reading center reading evaluation of DRSS (diabetic retinopathy severity scale) level based leakage index of OPTOS wide field fluorescein angiography. |
| Q4WKS | EXPERIMENTAL | Aflibercept 2 mg every 4 weeks (defined as every 28 days (+ 7 days) and at least 21 days between injections) through week 48. Following week 48, aflibercept 2 mg every 12 weeks through week 96. If NV or PDR are worse per pre-specified criteria at week 60, or at any study visit thereafter, the subject will be treated every 4 weeks through the end of the study. |
| Q12WKS | EXPERIMENTAL | Aflibercept 2 mg every 12-weeks. Subjects will be followed every 4 weeks through week 12, and can be treated if the pre-specified criteria are met. Starting at week 12 if NV or PDR are stable or improved (as assessed by investigator) the subject will be monitored and treated at a 12-week interval through week 48. If NV or PDR are worse per the pre-specified criteria at week 12, or at any study visit thereafter, the subject will be treated monthly through the end of the study. At week 52, aflibercept 2 mg every 4 weeks (defined as 28 days (+ 7 days) and at least 21 days between injections) for subjects with visible retinal non-perfusion. If retinal non-perfusion has completely resolved at week 72, aflibercept every 12 weeks through end of study. For subjects without retinal non-perfusion at week 52, aflibercept 2 mg every 12 weeks through the end of study. |
| aflibercept Q8 | ACTIVE_COMPARATOR | Administered every 8 weeks after a loading phase |
| High-Dose aflibercept Q12 | EXPERIMENTAL | Administered every 12 weeks after a loading phase |
| High-Dose aflibercept Q16 | EXPERIMENTAL | Administered every 16 weeks after a loading phase |
| intravitreal aflibercept injection (IAI) | EXPERIMENTAL | Treatment-naïve patients with neovascular "wet" age-related macular degeneration (nAMD) randomized in a 1:1 ratio |
| High-dose aflibercept (HD) | EXPERIMENTAL | Treatment-naïve patients with nAMD randomized in a 1:1 ratio |
| aflibercept injection (VEGF Trap-Eye, BAY86-5321) 0.5mg q4 | EXPERIMENTAL | - |
| aflibercept injection (VEGF Trap-Eye, BAY86-5321) 0.5mg q12 | EXPERIMENTAL | - |
| aflibercept injection (VEGF Trap-Eye, BAY86-5321) 2.0mg q4 | EXPERIMENTAL | - |
| aflibercept injection (VEGF Trap-Eye, BAY86-5321) 2.0mg q12 | EXPERIMENTAL | - |
| aflibercept injection (VEGF Trap-Eye, BAY86-5321) 4.0mg q12 | EXPERIMENTAL | - |
| Aflibercept in Non-Vitrectomized eyes | OTHER | Patients who have not had vitrectomy. |
| Intravitreal Aflibercept Injection | ACTIVE_COMPARATOR | Patients will be sequentially randomized to treatment with Aflibercept 2 mg via intravitreal injection (0.05 mL or 50 microliters) at the time of surgery. This will be administered post cataract excision by the Principal Investigator. The patient will be masked as to which Arm they are assigned. |
| Name | Type | Description |
|---|---|---|
| Aflibercept 8 mg | DRUG | Administered by intravitreal (IVT) injection |
| 8 mg aflibercept (BAY 86-5321) (High Dose) | DRUG | High-dose (HD) aflibercept is the sponsor's study intervention under investigation. Dose formulation: solution in vial. Unit dose strength: 114.3 mg/mL, Dosage Level: 8 mg (70 µL), Route of Administration: Intravitreal (IVT) injection every 16 weeks following 3 initial monthly doses. Packaging/ Labeling: Study Intervention will be provided in sterile 3 mL glass vials. Each vial will be labeled as required per country requirement. |
| 2 mg aflibercept (EYLEA, BAY 86-5321) | DRUG | Aflibercept 2 mg is the sponsor's active comparator. Dose formulation: solution in vial. Unit dose strength: 40 mg/mL, Dosage Level: 2 mg (50 µL), Route of Administration: Intravitreal (IVT) injection every 8 weeks following 5 initial monthly doses. Packaging/ Labeling: Study Intervention will be provided in sterile 2 mL glass vials. Each vial will be labeled as required per country requirement. Aflibercept 2 mg for the non-study "fellow eye" treatment is considered an auxiliary medicinal product (AxMP) in this study. Fellow eye treatment will be allowed with 2 mg aflibercept, at the investigator's discretion for indications approved by governing authorities. The treated fellow eye will not be considered an additional study eye. |
| Sham | OTHER | To preserve masking, sham injections will be performed for all participants at treatment visits in which participants do not receive an active injection through Week 56. Sham kits will be assigned for visits requiring sham injections. The sham kits are empty but should be handled in the same way as the active study intervention kits. Sham injections will be given on visits when an active injection is not planned. During the study treatment period all participants will receive either an active injection (8 mg or 2 mg aflibercept) or a sham injection (for masking purposes) following their assigned treatment group and eligibility for Dose regimen modification (DRM). |
| aflibercept | DRUG | Administered IVT |
| laser photocoagulation | PROCEDURE | Transpupillary conventional laser will be administered according to standard local procedures. |
| Aflibercept (EYLEA, BAY86-5321) | DRUG | 2 mg (0.05 mL), Intravitreal injection (IVT), single dose. |
| Topical IOP-lowering drugs | DRUG | A combination of at least 3 topical IOP-lowering drugs will be administered during a run-in phase before treatment and should be kept unchanged until IOP evaluation at Week 1, after which they may be reduced according to the investigator's opinion |
| Aflibercept (Eylea, BAY 86-5321) | DRUG | After the first aflibercept IVT injection on Day 1, subjects may receive sham injection at Week 1, and aflibercept injection at Week 5 and/or Week 9 if the re-treatment criteria are met. |
| Sham Injection | DRUG | After the first sham injection on Day 1, subjects may receive aflibercept IVT injection at Week 1, Week 5 and/or Week 9 if re-treatment criteria are met. |
| Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321) | BIOLOGICAL | Participants received 2mg Intravitreal aflibercept injection (IAI) (EYLEA, VEGF Trap-Eye, BAY86-5321) every 4 weeks (2Q4). |
| Macular Laser Photocoagulation | PROCEDURE | Participants received laser treatment at baseline and as needed at visits at which laser retreatment criteria were met, but no more frequently than every 12 weeks. |
| Visudyne | DRUG | Participants in the PDT group (Visudyne group) received Visudyne as needed. Additionally, sham IVT injections was administered until week 28. Thereafter, subjects in the PDT group received active (= no sham) VEGF Trap-Eye treatment until week 48. |
| Aflibercept Injection | DRUG | intravitreal 2mg aflibercept injection |
| High-dose aflibercept | DRUG | Intravitreally (IVT) administered as a liquid formulation in a vial |
| aflibercept injection (VEGF Trap-Eye, BAY86-5321) | BIOLOGICAL | Participants received 0.5 mg of aflibercept injection (VEGF Trap-Eye, BAY86-5321) at 4 week intervals through Week 12 |
Key Inclusion Criteria for Participants with nAMD: 1. ≥50 years of age 2. History of choroidal neovascularization (CNV) lesions secondary to nAMD in the eye study, requiring continued anti-VEGF treatment, as determined by the investigator. Key Inclusion Criteria for Participants with DME: 3. ≥1...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| EyePoint, Inc. | EYPT | 2 | PHASE3 | EYP-1901, Aflibercept |
| Oculis Holding AG | OCS | 2 | PHASE3 | Dexamethasone, Vehicle |
| Regeneron Pharmaceuticals, Inc. | REGN | 1 | PHASE3 | Aflibercept |
| AbbVie, Inc. | ABBV | 3 | PHASE2 | ABBV-RGX-314 Dose 1, Steroid, Aflibercept |
| Outlook Therapeutics, Inc. | OTLK | 1 | PHASE3 | bevacizumab |
| 4D Molecular Therapeutics, Inc. | FDMT | 1 | PHASE2 | 4D-150 IVT, Aflibercept IVT |
| Alvotech | ALVO | 1 | PHASE3 | AVT29, Eylea HD |
| Kiora Pharmaceuticals, Inc. | KPRX | 1 | PHASE2 | KIO-104 |
| REGENXBIO, Inc. | RGNX | 1 | PHASE2 | RGX-314 Dose 1, RGX-314 Dose 2, Aflibercept |
| Ocugen Inc | OCGN | 1 | PHASE1 | OCU200 |
| Adverum Biotechnologies, Inc. | ADVM | 1 | - | ADVM-022 |