A Study of the Efficacy, Safety, and Pharmacokinetics of A 36-Week Refill Regimen for the Port Delivery System With Ranibizumab in Patients With Neovascular Age-Related Macular Degeneration (Velodrome)

Study Overview
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Brief Summary
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Study WR42221 is a Phase IIIb, global, multicenter, randomized, visual assessor-masked study designed to assess the efficacy, safety, and pharmacokinetics of the Port Delivery System with ranibizumab (PDS) 100 mg/mL delivered every 36 weeks (Q36W) compared with every 24 weeks (Q24W) in patients with neovascular age-related macular degeneration (nAMD).

Official Title
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A Phase IIIb, Global, Multicenter, Randomized, Visual Assessor-Masked Study Of The Efficacy, Safety, And Pharmacokinetics Of A 36-Week Refill Regimen For The Port Delivery System With Ranibizumab In Patients With Neovascular Age-Related Macular Degeneration (Velodrome)

Conditions
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Neovascular Age-related Macular Degeneration (nAMD)

Intervention / Treatment
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* Drug: Ranibizumab
* Device: Port Delivery System with Ranibizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 50 years at time of signing Informed Consent Form Initial diagnosis of nAMD within 9 months prior to the screening visit Previous treatment with at least three anti- vascular endothelial growth factor (VEGF) intravitreal injections for nAMD per standard of care within 6 months prior to the screening visit Demonstrated response to prior anti-VEGF intravitreal treatment since diagnosis Availability of historical visual acuity data prior to the first anti-VEGF treatment for nAMD until the time of study enrollment BCVA of 34 letters (approximate 20/200 Snellen equivalent) or better Exclusion Criteria: History of vitrectomy surgery, submacular surgery, or other surgical intervention for AMD in study eye Prior treatment with Visudyne®, external-beam radiation therapy, or transpupillary thermotherapy in study eye Previous treatment with corticosteroid intravitreal injection, intraocular device implantation, previous laser (any type) used for AMD treatment in study eye Treatment with anti-VEGF agents other than ranibizumab within 1 month prior to the enrollment visit in study eye Concurrent conjunctival, Tenon's capsule, and/or scleral condition in the supero-temporal quadrant of the eye that may affect the implantation, subsequent tissue coverage, and refill-exchange procedure of the PDS implant Prior treatment with brolucizumab (at any time prior to the screening visit) in either eye Prior participation in a clinical trial involving any anti-VEGF drugs, within 6 months prior to the enrollment visit in either eye Subretinal hemorrhage that involves the center of the fovea, if the hemorrhage is >0.5 disc area at screening in study eye Subfoveal fibrosis or subfoveal atrophy in study eye CNV due to other causes, such as ocular histoplasmosis, trauma, central serous chorio-retinopathy, or pathologic myopia in either eye Retinal pigment epithelial tear in study eye Any concurrent intraocular condition that would either require surgical intervention during the study to prevent or treat visual loss that might result from that condition or affect interpretation of study results in study eye Active intraocular inflammation in study eye History of vitreous hemorrhage in study eye History of rhegmatogenous retinal detachment in study eye History of rhegmatogenous retinal tears or peripheral retinal breaks within 3 months prior to the enrollment visit in study eye History of pars plana vitrectomy surgery Aphakia or absence of the posterior capsule in study eye Spherical equivalent of the refractive error demonstrating more than 8 diopters of myopia in study eye Preoperative refractive error that exceeded 8 diopters of myopia, for Participants who have undergone prior refractive or cataract surgery in study eye Intraocular surgery within 3 months preceding the enrollment visit in study eye Uncontrolled ocular hypertension or glaucoma and any such condition the investigator determines may require a glaucoma-filtering surgery during a participant's participation in the study in study eye History of glaucoma-filtering surgery, tube shunts, or microinvasive glaucoma surgery in study eye History of corneal transplant in study eye Any history of uveitis requiring treatment in either eye Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye Uncontrolled blood pressure History of stroke within the last 3 months prior to informed consent Atrial fibrillation diagnosed or worsened within the last 3 months prior to informed consent History of myocardial infarction within the last 3 months prior to informed consent, History of other disease, metabolic dysfunction, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of ranibizumab or placement of the implant and that might affect interpretation of the results of the study or renders the participant at high risk of treatment complications in the opinion of the investigator Confirmed active systemic infection Use of any systemic anti-VEGF agents Active cancer within 12 months of enrollment except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, and prostate cancer with a Gleason score of <= 6 and a stable prostate-specific antigen for > 12 months Previous participation in any non-ocular disease studies of investigational drugs within 1 month preceding the informed consent Non-functioning non-study eye

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Phase 3b
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A [Q36W] 36-weeks between refill-exchange procedures<br>Participants randomized to the Q36W arm will receive PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) on a Q36W fixed interval. | Drug: Ranibizumab<br>* Arm A: Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 36-week intervals Arm B: Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals<br>Device: Port Delivery System with Ranibizumab<br>* Arm A: Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 36-week intervals Arm B: Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals<br>|
| Active Comparator: Arm B [Q24W] 24-weeks between refill-exchange procedures<br>Participants randomized to the Q24W arm will receive PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) on a Q24W fixed interval. | Drug: Ranibizumab<br>* Arm A: Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 36-week intervals Arm B: Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals<br>Device: Port Delivery System with Ranibizumab<br>* Arm A: Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 36-week intervals Arm B: Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Best-corrected visual acuity (BCVA) score averaged over Weeks 68 and 72, as assessed using the ETDRS chart starting at a distance of 4 meters | EDTRS = Early Treatment Diabetic Retinopathy Study. A vision score of 20/20 vision is considered normal. A score of 20/200 is considered being legally blind. | Baseline to Week 72 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in BCVA score over time |  | Baseline up to Week 72 | 
| Percentage of participants with BCVA score of 69 letters (approximate 20/40 Snellen equivalent) or better averaged over Weeks 68 and 72 |  | Baseline to Week 72 | 
| Percentage of participants with BCVA score of 69 letters (approximate 20/40 Snellen equivalent) or better over time |  | Baseline up to Week 72 | 
| Percentage of participants with BCVA score of 38 letters (approximate 20/200 Snellen equivalent) or worse averaged over Weeks 68 and 72 |  | Baseline to Week 72 | 
| Percentage of participants with BCVA score of 38 letters (approximate 20/200 Snellen equivalent) or worse over time |  | Baseline up to Week 72 | 
| Percentage of participants who report preferring ranibizumab 100 mg/mL delivered via the PDS compared with intravitreal treatment, as measured by the PDS Patient Preference Questionnaire (PPPQ) at At Weeks 24, 40 and 72 |  | At Weeks 24, 40, 72 | 
| Percentage of participants with bilateral disease who report preferring ranibizumab 100 mg/mL delivered via the PDS compared with intravitreal treatment, as measured by the PPPQ at At Weeks 24, 40 and 72 |  | At Weeks 24, 40, 72 | 
| Mean overall treatment satisfaction at Week 40, as measured by the Macular Disease Treatment Satisfaction Questionnaire (MacTSQ) total score in the Q36W arm compared with the Q24W arm |  | At Week 40 | 
| Percentage of participants who lose <10, <5, or gain >= 0 letters in BCVA score from baseline averaged over Weeks 68 and 72 |  | Baseline to Week 72 | 
| Percentage of participants who lose <10, <5, or gain >= 0 letters in BCVA score from baseline over time |  | Baseline up to Week 72 | 
| Incidence and severity of ocular and systemic (non-ocular) adverse events in the Q36W and Q24W arms |  | Baseline up to Week 72 | 
| Incidence, severity, and duration of adverse events of special interest, including ocular adverse events of special interest in the Q36W and Q24W arms |  | Baseline up to Week 72 | 
| Incidence, severity, and duration of ocular adverse events of special interest during the postoperative period (≤ 37 days of initial implantation) and follow-up period (> 37 days after implantation surgery) in all enrolled participants |  | Baseline up to Week 72 | 
| Incidence and severity of adverse device effects in the Q36W and Q24W arms |  | Baseline up to Week 72 | 
| Incidence, causality, severity, and duration of anticipated serious adverse device effects in the Q36W and Q24W arms |  | Baseline up to Week 72 | 
| Change from baseline in center point thickness (CPT) up to and including Week 72 |  | Baseline up to Week 72 | 
| Percentage of participants who do not undergo supplemental treatment with intravitreal ranibizumab 0.5 mg before each refill-exchange procedure |  | Week 16 to Week 68 | 
| Observed serum concentration of ranibizumab at specified timepoints |  | Baseline to Week 72 | 
| Incidence of treatment-emergent ADAs during the study |  | Baseline to Week 72 |