Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as ITV-1, ITV-2, Aflibercept
VEGF Trap · 22 trials · 16 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.
BCVA: Best-Corrected Visual Acuity; ETDRS: Early Treatment Diabetic Retinopathy Study; ETDRS letter score (ranging from 0 to 100 letters). A higher letter score means a better outcome (better visual acuity)
AE: adverse event SAE: serious adverse event
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.
Active ROP was defined as ROP requiring treatment. Unfavorable structural outcomes included retinal detachment, macular dragging, macular fold, or retrolental opacity.
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.
Defined study baseline range of Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score of 73 to 24 (= Acuity of 20/40 to 20/320) in the study eye; a higher score represents better functioning. Nominator = (Number of participants who maintained vision \* 100); Denominator = Number of participants analyzed.
Maintenance of vision was defined as a loss of \< 15 letters in the ETDRS (Early Treatment Diabetic Retinopathy Study) letter score (defined study baseline range of ETDRS Best Corrected Visual Acuity letter score of 73 to 25 (= Acuity of 20/40 to 20/320) in the study eye; a higher score represents better functioning. Nominator = (Number of participants who maintained vision \* 100); Denominator = Number of participants analyzed.
Defined "maintenance of vision" as patients who lost fewer than 15 letters in Early Treatment Diabetic Retinopathy Study (ETDRS) letter score compared to baseline.
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.
Number of participants with ocular and non-ocular adverse events (AEs) in both treatment arms.
The primary endpoint in the study consists of intraocular aflibercept (free and bound) concentrations following intravitreal aflibercept injection.
| 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. |
| Higher Dose Regimen 1 | EXPERIMENTAL | Higher dose of aflibercept is administered with initial initiation doses intervals, followed by extension of treatment intervals and further adjustment of intervals according to treatment response. |
| Higher Dose Regimen 2 | EXPERIMENTAL | Higher dose of aflibercept is administered with initial initiation doses intervals, followed by extension of treatment intervals and further adjustment of intervals according to treatment response. |
| Standard of care | ACTIVE_COMPARATOR | Aflibercept 2 mg is administered by standard treatment intervals, followed by adjustment of treatment intervals according to treatment response. |
| Aflibercept arm | EXPERIMENTAL | No study treatment will be administered. The treatments to be evaluated in this study were administered in Study 20090. |
| Laser photocoagulation arm | ACTIVE_COMPARATOR | No study treatment will be administered. The treatments to be evaluated in this study were administered in Study 20090. |
| 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. |
| Sham treatment | SHAM_COMPARATOR | Participants received sham treatment administered every 4 weeks from Day 1 through Week 52. Follow-up phase: Participants on sham treatment, who switched to Intravitreal Aflibercept Injection (IAI), received a 2 mg dose of IAI at week 52 and depending on the study retreatment criteria at Week 60 and 68. |
| Ranibizumab 0.5mg Q4 | ACTIVE_COMPARATOR | Participants received a 0.5 mg dose of Ranibizumab via intravitreal (IVT) injection administered every 4 weeks for the first year. Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks. |
| Aflibercept Injection (EYLEA, VEGF Trap-Eye) 2mg Q4 | EXPERIMENTAL | Participants received a 2.0 mg dose of Aflibercept Injection administered every 4 weeks for the first year. Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks. |
| Aflibercept Injection (EYLEA, VEGF Trap-Eye) 0.5mg Q4 | EXPERIMENTAL | Participants received a 0.5 mg dose of Aflibercept Injection administered every 4 weeks for the first year. Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks. |
| Aflibercept Injection (EYLEA, VEGF Trap-Eye) 2mg Q8 | EXPERIMENTAL | Participants received a 2.0 mg dose of Aflibercept Injection administered every 8 weeks (including one additional 2,0 mg dose at Week 4) for the first year. Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks. |
| aflibercept injection 2.0mg Q4 | EXPERIMENTAL | - |
| aflibercept injection 0.5mg Q4 | EXPERIMENTAL | - |
| aflibercept injection 2.0mg Q8 | EXPERIMENTAL | - |
| 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 | - |
| 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. |
| Aflibercept in Non-Vitrectomized eyes | OTHER | Patients who have not had vitrectomy. |
| ITV-1 | EXPERIMENTAL | VEGF Trap formulation 1 |
| ITV-2 | EXPERIMENTAL | VEGF Trap formulation 2 |
| ITV-2 OL | EXPERIMENTAL | VEGF Trap formulation 2 open label, higher concentration |
| Part A | EXPERIMENTAL | Part A: An open label study in which six successive cohorts of 3-6 patients each with neovascular AMD will receive a single intravitreal (ITV) injection of 0.05, 0.15, 0.5, 1.0, 2.0, or 4.0 mg of VEGF Trap into the study eye. The total volume of each injection will be 100 μL. Enrollment in new dose levels will not begin until all patients in the preceding dose level have completed Visit 5 (Day 15). |
| Part B | ACTIVE_COMPARATOR | Part B: A controlled, prospective, randomized, double-masked study in which up to 30 subjects meeting eligibility criteria will be randomly assigned in a 1:1 ratio to receive a single ITV injection of2.0 mg/eye VEGF Trap (or the MTD if reached prior to 2.0 mg) followed by 1 sham injection six weeks later, or an initial dose of 0.3 mg pegaptanib sodium into the study eye, followed by a second dose six weeks later. Enrollment into Part B will begin 2 weeks after the last subject to receive the 2.0 mg/eye dose in Part A has been observed for 15 days and it has been determined that the safety profile of VEGF Trap at this dose level is adequate to support expansion of dosing at this dose level. The dose of pegaptanib sodium will be 0.3 mg, according to the package insert. |
| Part C | ACTIVE_COMPARATOR | Part C: A controlled, prospective, randomized, double-masked study in which approximately 30 subjects meeting eligibility criteria will be randomly assigned in a 1:1 ratio to receive up to two ITV injections of either 0.15 or 4.0 mg/eye VEGF Trap. Initiation of Part C is contingent upon the 4.0 mg dose being adequately tolerated in Part A. |
| 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, VEGF Trap-Eye(Eylea, BAY86-5321)_higher dose | DRUG | Intravitreally (IVT) injection. |
| Aflibercept, VEGF Trap-Eye(Eylea, BAY86-5321)_2 mg | DRUG | Intravitreally (IVT) injection. |
| Fluorescein | DIAGNOSTIC_TEST | Fluorescein 100 mg/mL solution for injection is a dye that makes the retinal vessels visible during FA examinations, and as such, it will be used as an auxiliary medicinal product (AxMP) in this periodic ophthalmic examination. This medicine is for diagnostic use only. It is not used to treat any condition. |
| Eylea (Aflibercept, BAY86-5321) | DRUG | Treatment administered in 20090. Solution in a sterile glass vial, Dose A, IVT injection. |
| Laser photocoagulation | PROCEDURE | Treatment administered in 20090. Transpupillary conventional laser ablative therapy |
| aflibercept | DRUG | Administered IVT |
| 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 (EYLEA, VEGF Trap-Eye, BAY86-5321) | BIOLOGICAL | Intravitreal injection. Weeks 0 to 20 of Aflibercept Injection every 4 weeks; Weeks 24 to 52 every 4 weeks PRN (pro re nata, on demand); plus additional on Week 60 and 68. |
| Sham treatment | OTHER | Sham treatment. Weeks 0 to 52 sham treatment every 4 weeks; plus additional on Week 60 and 68. |
| Ranibizumab | DRUG | Participants received a 0.5 mg dose of Ranibizumab via intravitreal (IVT) injection administered every 4 weeks for the first year. Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks. |
| aflibercept injection (VEGF Trap-Eye, BAY86-5321) | BIOLOGICAL | Participants received a 2.0mg dose of aflibercept injection every 4 weeks for the first year. Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks. |
| Aflibercept Injection | DRUG | intravitreal 2mg aflibercept injection |
| High-dose aflibercept | DRUG | Intravitreally (IVT) administered as a liquid formulation in a vial |
| VEGF Trap | DRUG | VEGF Trap formulation 1, ITV-1 |
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 |
|---|---|---|---|---|
| AbbVie, Inc. | ABBV | 7 | PHASE3 | Surabgene Lomparvovec, RGX-314, ABBV-6628 |
| Ocular Therapeutix Inc | OCUL | 3 | PHASE3 | OTX-TKI |
| 4D Molecular Therapeutics, Inc. | FDMT | 3 | PHASE3 | 4D-150 |
| Regeneron Pharmaceuticals, Inc. | REGN | 2 | PHASE3 | Aflibercept, Pozelimab, Cemdisiran |
| Novartis AG Sponsored ADR | NVS | 5 | PHASE2 | Iptacopan, GT005, FWY003 |
| EyePoint, Inc. | EYPT | 2 | PHASE3 | EYP-1901 |
| Kodiak Sciences, Inc. | KOD | 1 | PHASE3 | Tarcocimab tedromer, Tabirafusp tedromer |
| Hoffmann-La Roche | RHHBY | 10 | PHASE3 | Ranibizumab, Susvimo, RO7965032, OpRegen, Faricimab |
| Outlook Therapeutics, Inc. | OTLK | 1 | PHASE3 | ONS-5010 |
| Adverum Biotechnologies, Inc. | ADVM | 4 | PHASE3 | Ixo-vec, ADVM-022 |
| Apellis Pharmaceuticals, Inc. | APLS | 1 | PHASE2 | APL-3007 |
| Amgen Inc. | AMGN | 1 | PHASE3 | ABP 938, Aflibercept |
| Johnson & Johnson | JNJ | 1 | PHASE2 | JNJ-81201887 |
| Ocugen Inc | OCGN | 1 | PHASE3 | OCU410 |
| Alcon AG | ALC | 1 | PHASE1 | AR-14034 |
| Sanofi SA Sponsored ADR | SNY | 1 | PHASE1 | SAR402663 |
| Arrowhead Pharmaceuticals, Inc. | ARWR | 1 | PHASE1 | ARO-033 |
| Bayer | BAYRY | 2 | - | Aflibercept |
VEGF Trap is an investigational small molecule being studied for the treatment of neovascular age-related macular degeneration and macular degeneration. It is administered via intravitreal injection and is currently in Phase 1 clinical development.
VEGF Trap is being developed by Regeneron Pharmaceuticals, Inc., a biopharmaceutical company traded on the NASDAQ under the ticker symbol REGN. The company is conducting clinical trials to evaluate the safety and tolerability of the drug.
VEGF Trap is in Phase 1 clinical development. Two Phase 1 trials have been completed, each evaluating the safety and tolerability of intravitreal VEGF Trap administration in patients with neovascular age-related macular degeneration.
VEGF Trap has been studied in two completed Phase 1 clinical trials: NCT00320775, which enrolled 51 patients with macular degeneration, and NCT00383370, which enrolled 20 patients with neovascular age-related macular degeneration. Both trials were conducted in the United States.
VEGF Trap is the investigational name for the drug that is also known as aflibercept. The clinical trials listed under the name VEGF Trap evaluate the same active agent, which is being developed by Regeneron Pharmaceuticals for ophthalmic use.