Study of EYP-1901 in Subjects With Wet Age Related Macular Degeneration (wAMD)
- Conditions
- Wet Age-related Macular Degeneration
- Interventions
- Registration Number
- NCT05381948
- Lead Sponsor
- EyePoint Pharmaceuticals, Inc.
- Brief Summary
This is a phase 2 randomized, double -masked study comparing the efficacy of EYP-1901 at 2 dose levels: 2060 microgram (mcg) and 3090 mcg against aflibercept.
- Detailed Description
This study is evaluating the 2 doses of EYP-1901 against aflibercept in a randomized study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 161
- Documented diagnosis of wAMD in the study eye, with disease onset any time prior to the Screening Visit.
- Documented anatomical response (that is, reduction in fluid on [spectral-domain - optical coherence tomography (SD-OCT)] to previous intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections in the study eye prior to the Screening Visit.
- Previously treated with at least 2 anti-VEGF intravitreal injections (that is, bevacizumab, ranibizumab, aflibercept or faricimab) for wAMD per standard of care in the study eye within 6 months prior to the Screening Visit.
- Received previous anti-VEGF therapy 2 to 5 weeks (14 to 35 days) in the study eye prior to Screening Visit, but no more than 42 days prior to randomization to study treatment on Day 1.
- Best corrected visual acuity (BCVA) early Treatment Diabetic Retinopathy Study (ETDRS) letter score of 35 letters (20/200 Snellen equivalent) to 85 letters (20/20 Snellen equivalent) in the study eye at the Screening Visit and on Day 1.
- Able to understand, and willingness to sign, the informed consent and to provide access to personal health information via Health Insurance Portability and Accountability Act (HIPAA) authorization.
- Willingness and ability to comply with all scheduled visits, restrictions, and assessments.
- For women of childbearing potential, or men with female partners of childbearing potential, agreement to the use of an appropriate form of contraception at the Screening Visit and for the duration of the study.
- History of pars plana vitrectomy surgery, submacular surgery, or other surgical intervention for AMD in the study eye.
- Prior treatment with Visudyne® (verteporfin), external beam radiation therapy, or transpupillary thermotherapy in the study eye.
- Previous treatment with intravitreal corticosteroid injection or device implantation in the study eye.
- Previous focal laser photocoagulation used for AMD treatment in the study eye.
- Total choroidal neovascularization (CNV) lesion size >12 disc areas [30.5 millimeter square (mm^2)] as assessed by fluorescein angiography (FA) in the study eye at the Screening Visit.
- Central subfield thickness (CST) >350 micrometer (mcm) in the study eye at the Screening Visit or Day 1.
- Intraretinal cystic fluid >25 mcm in diameter involving the central subfield and/or disruption of normal morphology (loss of foveal depression, disruption of external limiting membrane) secondary to cystic intraretinal fluid within the central subfield, in the study eye at the Screening Visit. Diffuse (non-cystic) intraretinal fluid would not be excluded.
- Subretinal hemorrhage in the subfoveal/juxtafoveal location and hemorrhage greater than 1 disc are (1.8 mm^2) if located less than 200 mcm from the foveal center in the study eye at either the Screening Visit or Day 1.
- Subfoveal fibrosis, atrophy, or scarring in the center subfield in the study eye at the Screening Visit.
- Fibrosis >50% of the total lesion, in the study eye at the Screening Visit.
- Retinal pigment epithelium detachment (RPED) thickness >400 mcm at any point within 3 mm of the foveal center in the study eye at either the Screening Visit or Day 1.
- Retinal pigment epithelial tear in the study eye at the Screening Visit or Day 1.
- Any concurrent intraocular condition in the study eye (e.g., cataract or glaucoma) that, in the opinion of the investigator, would have either required surgical intervention during the study to prevent or treat visual loss that might result from that condition or affected interpretation of the study results.
- Historical or active intraocular inflammation (grade trace or above) in the study eye, other than expected findings from routine cataract surgery.
- History of vitreous hemorrhage in the study eye within 12 weeks prior to the Screening Visit.
- History of rhegmatogenous retinal detachment or treatment for retinal detachment or macular hole (stage 3 or 4) in the study eye.
- Aphakia or pseudophakia with the absence of the posterior capsule in the study eye (YAG capsulotomy is permitted).
- Spherical equivalent of the refractive error in the study eye demonstrating >8 diopters of myopia.
- For subjects who have undergone prior refractive or cataract surgery in the study eye, preoperative refractive error in the study eye exceeding 8 diopters of myopia.
- Intraocular surgery (including cataract surgery) in the study eye within 12 weeks prior to the Screening Visit.
- Uncontrolled ocular hypertension or glaucoma in the study eye (defined as intraocular pressure (IOP) >25 mm of mercury (mmHg) or a cup to disc ratio >=0.8, despite treatment with 2 or more classes of antiglaucoma medication) and any such condition which the Investigator feels may require a glaucoma-filtering surgery while in the study.
- History of glaucoma-filtering surgery, tube shunts, or microinvasive glaucoma surgery in the study eye.
- History of corneal transplant in the study eye.
- BCVA using ETDRS charts <30 letters (20/250 Snellen equivalent) in the fellow eye.
- Worsening of BCVA ≥10 ETDRS letters in the study eye from the Screening Visit to Day 1.
- Presence of CNV in either eye due to other causes aside from wAMD at the Screening Visit.
- Treatment with Visudyne® in the fellow eye <7 days prior to the Screening Visit.
- Prior participation in a clinical trial involving investigational anti-angiogenic drugs administered in either eye or systemically within 8 weeks prior to the Screening Visit.
- Prior participation in a clinical trial involving investigational ocular gene therapy trial for either eye.
- History of idiopathic or autoimmune-associated uveitis in either eye.
- Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye.
- Presence of any other systemic or ocular condition which, in the judgment of the investigator, could make the subject inappropriate for entry into this study.
- Uncontrolled blood pressure (defined as systolic >180 mmHg and/or diastolic >100 mmHg), based on the average of three readings taken with the subject in a resting state.
- Myocardial infarction within 6 months prior to screening or New York Hospital Association (NYHA) Class III or IV heart failure, uncontrolled atrial fibrillation, uncontrolled angina, cardiomyopathy, ventricular arrhythmias or other cardiac conditions which, in the judgment of the investigator, could make the subject inappropriate for entry into this study.
- Serious non-healing wound, ulcer, or bone fracture.
- Glycated hemoglobin (HbA1c) greater than 7% at the Screening Visit.
- History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of EYP-1901.
- Current treatment for any active systemic infection.
- Previous use of any systemic anti-VEGF agents or intraocular brolucizumab in the study eye.
- Use of oral corticosteroids (prednisone >10 mg/day or equivalent) within 30 days prior to the Screening Visit.
- History or presence of bleeding disorders, including platelet disorders, hemorrhage, acquired or hereditary coagulation disorders (including deep vein thrombosis and pulmonary embolisms), acquired or hereditary vascular disorders, stroke, or transient ischemic attack.
- Excluding certain skin cancers (specifically, basal cell carcinoma and squamous cell carcinoma), any malignancy receiving treatment, or in remission less than 5 years prior to study entry.
- History of allergy to fluorescein, not amenable to treatment.
- Inability to obtain fundus photographs, FA, fundus autofluorescence, or SD-OCT images of sufficient quality to be analyzed and graded by the Central Reading Center.
- Historical or active diagnosis of any medical or psychological condition that could interfere with the ability of the subject to give informed consent, or to comply with study or follow-up procedures.
- Previous participation in any ocular or non-ocular (systemic) disease studies of investigational drugs within 30 days prior to the Screening Visit (excluding vitamins and minerals).
- Use of anti-mitotic or anti-metabolite therapy within 30 days or 5 elimination half-lives of the Screening Visit, whichever is longer.
- Intolerance, contraindication, or hypersensitivity to topical anesthetics, dyes, povidone iodine, mydriatic medications, or any of the ingredients of the EYP-1901 insert.
- Requirement for continuous use of any protocol-prohibited medications or treatments.
- Pregnant or nursing females; females of childbearing potential who are unwilling or unable to use an acceptable method of contraception during the study as outlined in this protocol.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description EYP-1901 2060 mcg EYP-1901 EYP-1901 2060 mcg, single dose EYP-1901 3090 mcg EYP-1901 EYP-1901 3090 mcg, single dose Aflibercept Aflibercept 2mg/0.05mL Inj,Oph Aflibercept 2 milligram (mg) \[0.05 milliliter (mL)\] every 8 weeks
- Primary Outcome Measures
Name Time Method Average Change in Best Corrected Visual Acuity (BCVA) From Baseline Averaged Over Weeks 28 and 32 Baseline (Day 1) and Weeks 28 and 32 The BCVA was measured according to the standard procedure originally developed for Early Treatment Diabetic Retinopathy Study (ETDRS). The ETDRS letter score calculated when 20 or more letters were read correctly at 4.0 meters; the visual acuity letter score was equal to the total number of letters read correctly at 4.0 meters plus 30. The score ranges from 0 (worse) to 100 (best). Higher scores indicate positive outcome measure. Baseline was defined as the last non-missing measurement before the initiation of study treatment.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Best Corrected Visual Acuity up to Week 56 Baseline (Day 1) and Weeks 32 and 56 The BCVA was measured according to the standard procedure originally developed for ETDRS. The ETDRS letter score calculated when 20 or more letters were read correctly at 4.0 meters; the visual acuity letter score was equal to the total number of letters read correctly at 4.0 meters plus 30. The score ranges from 0 (worse) to 100 (best). Higher scores indicate positive outcome measure. Baseline was defined as the last non-missing measurement before the initiation of study treatment.
Percentage of Subjects With >=5, >=10, and >=15 BCVA Letter Change From Baseline up to Week 56 Baseline (Day 1) and Weeks 32 and 56 The BCVA was measured according to the standard procedure originally developed for ETDRS. The ETDRS letter score calculated when 20 or more letters were read correctly at 4.0 meters; the visual acuity letter score was equal to the total number of letters read correctly at 4.0 meters plus 30. The score ranges from 0 (worse) to 100 (best). Higher scores indicate positive outcome measure. Baseline was defined as the last non-missing measurement before the initiation of study treatment.
Percentage of Subjects Not Receiving Supplemental Injection of Aflibercept up to Week 56 Weeks 32 and 56 Supplemental therapy was any unscheduled injection of aflibercept, whether or not a subject had met rescue criteria. For the aflibercept arm, any aflibercept injection following Week 8 which did not occur at Weeks 16, 24, 32, 40, 48, or 56, was supplemental therapy. For either of the EYP-1901 arms, any aflibercept injection following the Week 8 visit was supplemental therapy.
Median Time to First Supplemental Aflibercept Injection in the Study Eye Following the EYP-1901 Dose at Week 8 From Week 8 to Week 56 Time to first supplemental aflibercept injection following Week 8 study treatment was defined as the date of the first supplemental aflibercept injection minus the date of the Week 8 study treatment administration, divided by 7 days per week. Subjects who did not receive any supplemental aflibercept injection following study treatment administration at Week 8 were censored at their date of last visit (those who completed) or date of last contact (those who discontinued the study early).
Number of Aflibercept Intravitreal Injections up to Week 56 (Including Loading Dose) Weeks 32 and 56 Normalized number of aflibercept injections including loading dose was calculated as (number of aflibercept injections received plus all loading doses received) / (time within study period in months), multiplied by 6 months (Week 32) or 12 months (Week 56).
Mean Change From Baseline in Central Subfield Thickness (CST) by Spectral-Domain - Optical Coherence Tomography (SD-OCT) up to Week 56 Baseline (Day 1) and Weeks 32 and 56 The SD-OCT assessments in study eye was taken by a study-certified OCT technician according to the standardized procedures described in the Study Manual. Baseline was defined as the last non-missing measurement before the initiation of study treatment.
Change From Baseline in Height of Subretinal Fluid by Spectral-Domain - Optical Coherence Tomography up to Week 56 Baseline (Day 1) and Weeks 32 and 56 The SD-OCT assessments in study eye was taken by a study-certified OCT technician according to the standardized procedures described in the Study Manual. Baseline was defined as the last non-missing measurement before the initiation of study treatment.
Percentage of Subjects With No Detectable Intraretinal Fluid/Cysts in the Central Subfield up to Week 56 Weeks 32 and 56 The percentage of subjects with no detectable intraretinal fluid/cysts in the central subfield were summarized by scheduled visit and for any time post-baseline visits. Intraretinal fluid was assessed for the categories 'Absent', 'Present, not clinically significant', 'Present, clinically significant' and 'Not Done'. If intraretinal fluid assessment at any scheduled visit fell under the category 'Absent or Present, not clinically significant', then it was considered as no detectable intraretinal fluid in that scheduled visit.
Change From Baseline in Total Lesion Area by Fluorescein Angiography (FA) up to Week 56 Baseline (Day 1) and Weeks 32 and 56 The total lesion area was defined as the active vascular component \[classic and occult choroidal neovascularization (CNV)\] and the non-vascular/fibrotic component (fibrosis, serous pigment epithelial detachment, elevated blocking hemorrhage or hyperplastic pigment). Baseline was defined as the last non-missing measurement before the initiation of study treatment.
Change From Baseline in Total Choroidal Neovascularization Area by Fluorescein Angiography up to Week 56 Baseline (Day 1) and Weeks 32 and 56 The total CNV area included the measured area of classic and occult components. Baseline was defined as the last non-missing measurement before the initiation of study treatment.
Systemic Exposure to EYP-1901 Measured Through Plasma Levels up to Week 56 Up to Week 56 Blood samples were collected at the study visits to determine the EYP-1901 and its main metabolite concentrations.
Ocular Exposure to EYP-1901 Measured Through Aqueous Humor (AH) Levels up to Week 32 Up to Week 32 The AH samples were collected at the study visits to determine the EYP-1901 and its main metabolite concentrations.
Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Serious Treatment-Emergent Adverse Events up to Week 56 From the study drug administration (Day 1) up to end of the study, approximately 56 weeks. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a patient or clinical investigation subject administered an investigational or marketed (medicinal) product and that does not necessarily have a causal relationship with the product. An serious AE is any AE that results in one of the following outcomes: death; life-threatening; requires in-patient hospitalization; results in a persistent or significant disability/incapacity; congenital anomaly/birth defect; other important medical event. The TEAEs are AEs that occur after the first dose of study treatment.
administration.
Trial Locations
- Locations (2)
EyePoint Investigative Site
🇺🇸Silverdale, Washington, United States
EyePoint Investigative Sites
🇺🇸Houston, Texas, United States
EyePoint Investigative Site🇺🇸Silverdale, Washington, United States