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)

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)

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Neovascular Age-related Macular Degeneration (nAMD)
• Intervention / Treatment: Drug: Ranibizumab; Device: Port Delivery System with Ranibizumab

• Study Type: Interventional
• Enrollment (Actual): 451
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Capital Federal, Argentina, C1120AAN
    • Oftalmos
  • Capital Federal, Argentina, C1116
    • Centro Oftalmologico Dr. Charles S.A.
  • Rosario, Argentina, S2000DLA
    • Grupo Laser Vision
• Australia
  • New South Wales
    • Albury, New South Wales, Australia, 2640
      • Eyeclinic Albury Wodonga
    • Hurstville, New South Wales, Australia, 2220
      • Eye and Retina Consultants
    • Liverpool, New South Wales, Australia, 2170
      • Retina Associates Liverpool
    • Miranda, New South Wales, Australia, 2228
      • Retina and Macula Specialists
    • Sydney, New South Wales, Australia, 2000
      • Sydney Eye Hospital
    • Sydney, New South Wales, Australia, 2000
      • Sydney Retina Clinic and Day Surgery
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Queensland Eye Institute
  • Victoria
    • East Melbourne, Victoria, Australia, 3002
      • Centre for Eye Research Australia
    • Rowville, Victoria, Australia, 3178
      • Retina Specialists Victoria
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • The Lions Eye Institute
• Austria
  • Graz, Austria, 8036
    • LKH-Univ.Klinikum Graz
  • Vienna, Austria, 1090
    • Medizinische Universitat Wien
• Belgium
  • Leuven, Belgium, 3000
    • UZ Leuven Gasthuisberg
• Brazil
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil
      • Hospital das Clinicas - UFRGS
  • Santa Catarina
    • Blumenau, Santa Catarina, Brazil, 89052-504
      • Botelho Hospital da Visao
  • São Paulo
    • Sorocaba, São Paulo, Brazil, 18031-060
      • Hosp de Olhos de Sorocaba
    • São Paulo, São Paulo, Brazil, 04023-062
      • Universidade Federal de Sao Paulo - UNIFESPX
    • São Paulo, São Paulo, Brazil, 01427-002
      • Retina Clinic
    • São Paulo, São Paulo, Brazil, 04038-032
      • Instituto da Visao IPEPO
• France
  • Bordeaux, France, 33000
    • Centre Retine Gallien
  • Lyon, France, 69317
    • Hôpital de la Croix Rousse
  • Marseille, France, 13008
    • Centre Paradis Monticelli
  • Paris, France, 75010
    • Hôpital Lariboisière
  • Paris, France, 75940
    • Fondation Rothschild
• Germany
  • Bonn, Germany, 53127
    • Universitatsklinikum Bonn
  • Cologne, Germany, 50937
    • Universitatsklinikum Koln
  • Cottbus, Germany, 03048
    • Medizinische Universitat Lausitz ? Carl Thiem
  • Freiburg im Breisgau, Germany, 79106
    • Universitätsklinikum Freiburg, Klinik für Augenheilkunde
  • Hamburg, Germany, 20246
    • Universitatsklinikum Hamburg-Eppendorf
  • Ludwigshafen, Germany, 67063
    • Klinikum der Stadt Ludwigshafen am Rhein gGmbH
  • München, Germany, 80336
    • LMU Klinikum der Universitat, Augenklinik
  • Münster, Germany, 48149
    • Universitatsklinikum Munster
  • Münster, Germany, 48145
    • Augenabteilung am St. Franziskus-Hospital
  • Sulzbach, Germany, 66280
    • Knappschaftsklinikum Saar GmbH
  • Tübingen, Germany, 72076
    • Universitatsklinikum Tubingen
  • Ulm, Germany, 89075
    • Universitatsklinikum Ulm, Augenklinik und Poliklinik
• Israel
  • Haifa, Israel, 3109601
    • Rambam Medical Center
  • Jerusalem, Israel, 9112001
    • Hadassah MC
  • Kfar Saba, Israel, 4428164
    • Meir Medical Center
  • Petah Tikva, Israel, 4941492
    • Rabin MC
  • Rehovot, Israel, 7660101
    • Kaplan Medical Center
  • Tel Aviv, Israel, 6423906
    • Tel Aviv Sourasky MC
• Italy
  • Abruzzo
    • Chieti, Abruzzo, Italy, 66100
      • Ospedale Clinicizzato SS Annunziata
  • Apulia
    • Bari, Apulia, Italy, 70124
      • Policlinico di Bari
  • Friuli Venezia Giulia
    • Trieste, Friuli Venezia Giulia, Italy, 34129
      • Azienda Ospedaliero Universitaria "Ospedali Riuniti" Trieste-Ospedale Maggiore
  • Lazio
    • Rome, Lazio, Italy, 00168
      • Policlinico Universitario Agostino Gemelli
    • Rome, Lazio, Italy, 00198
      • Fondazione G.B. Bietti Per Lo Studio E La Ricerca in Oftalmologia-Presidio Ospedaliero Britannico
  • Lombardy
    • Milan, Lombardy, Italy, 20132
      • IRCCS Ospedale San Raffaele
    • Milan, Lombardy, Italy, 20100
      • Fondazione Irccs Ca' Granda Ospedale Maggiore Policlinico-Clinica Regina Elena
    • Milan, Lombardy, Italy, 20157
      • ASST Fatebenefratelli Sacco
  • The Marches
    • Torrette - Ancona, The Marches, Italy, 60126
      • Azienda Ospedaliero Universitaria Ospedali Riuniti
  • Tuscany
    • Florence, Tuscany, Italy, 50134
      • Azienda Ospedaliero-Universitaria Careggi
  • Umbria
    • Perugia, Umbria, Italy, 06129
      • Azienda Ospedaliera di Perugia Ospedale S. Maria Della Misericordia
  • Veneto
    • Negrar - Verona, Veneto, Italy, 37024
      • Ospedale Classificato Equiparato Sacro Cuore ? Don Calabria
    • Udine, Veneto, Italy, 33100
      • A.O. Universitaria S. Maria Della Misericordia Di Udine
• Singapore
  • Singapore, Singapore, 119074
    • National University Hospital
  • Singapore, Singapore, 308433
    • Tan Tock Seng Hospital
  • Singapore, Singapore, 168751
    • Singapore Eye Research Institute
• South Korea
  • Busan, South Korea, 49241
    • Pusan National University Hospital
  • Daegu, South Korea, 42415
    • Yeungnam University Medical Center
  • Incheon, South Korea, 21565
    • Gachon University Gil Medical Center
  • Seongnam-si, South Korea, 13605
    • Seoul National University Bundang Hospital
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
  • Seoul, South Korea, 05505
    • Asan Medical Center
  • Seoul, South Korea, 06351
    • Samsung Medical Center
  • Seoul, South Korea, 02447
    • Kyung Hee University Hospital
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08022
    • Institut de la Macula i la retina
  • Barcelona, Spain, 08025
    • Hospital dos de maig
  • Barcelona, Spain, 08021
    • Centro de Oftalmologia Barraquer
  • Córdoba, Spain, 14012
    • Hospital de la Arruzafa. Servicio de Oftalmologia
  • Madrid, Spain, 28046
    • Clinica Baviera
  • Valencia, Spain, 46004
    • Oftalvist Valencia
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Hospital Universitario de Bellvitge
    • San Cugat Del Valles, Barcelona, Spain, 08195
      • Hospital General de Catalunya
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Universitario Puerta de Hierro
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Clinica Universitaria de Navarra
  • Principality of Asturias
    • Oviedo, Principality of Asturias, Spain, 33012
      • Instituto Oftalmologico Fernandez Vega
• Switzerland
  • Basel, Switzerland, 4056
    • Universitatsspital Basel Augenklinik Klinik
  • Bern, Switzerland, 3010
    • Inselspital Bern Ophthalmologische Klinik
  • Binningen, Switzerland, 4102
    • Vista Klinik Ophthalmologische Klinik
  • Lausanne, Switzerland
    • Fondation Asile Des Aveugles ? Jules Gonin Eye Hospital
  • Zurich, Switzerland, 8063
    • Stadtspital Triemli Ophthalmologische Klinik
• Taiwan
  • Changhua, Taiwan, 500
    • Changhua Christian Hospital
  • Kaohsiung City, Taiwan
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
  • Taoyuan, Taiwan, 333
    • Chang Gung Medical Foundation - Linkou
  • Zhongzheng Dist., Taiwan, 10002
    • National Taiwan University Hospital
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06490
    • Ankara Bilkent City Hospital
  • Ankara, Turkey (Türkiye), 06100
    • Hacettepe University Medical Faculty
  • Ankara, Turkey (Türkiye)
    • Ankara Etlik City Hospital
  • Istanbul, Turkey (Türkiye), 34421
    • Beyoglu Goz Training and Research Hospital
  • Kocaeli, Turkey (Türkiye), 41380
    • Kocaeli Universitesi T?p Fakultesi
• United Kingdom
  • Bristol, United Kingdom, BS1 2LX
    • Bristol Eye Hospital
  • Liverpool, United Kingdom, L7 8XP
    • Royal Liverpool University Hospital
  • London, United Kingdom, EC1V 2PD
    • Moorfields Eye Hospital NHS Foundation Trust
  • London, United Kingdom, SE5 9RS
    • Kings College Hospital
  • London, United Kingdom, NW10 7NS
    • Central Middlesex Hospital
  • Newcastle upon Tyne, United Kingdom, NE1 4LP
    • Royal Victoria Infirmary
  • Sunderland, United Kingdom, SR2 9HP
    • Sunderland Eye Infirmary
  • Wolverhampton, United Kingdom, WV10 0QP
    • New Cross Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 9 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
• Choroidal neovascularization (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 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A [Q36W] 36-weeks between refill-exchange procedures; Participants randomized to the Q36W arm will receive PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) on a Q36W fixed interval.	Drug: Ranibizumab; 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; Device: Port Delivery System with Ranibizumab; 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
Active Comparator: Arm B [Q24W] 24-weeks between refill-exchange procedures; Participants randomized to the Q24W arm will receive PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) on a Q24W fixed interval.	Drug: Ranibizumab; 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; Device: Port Delivery System with Ranibizumab; 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

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): July 14, 2021
• Primary Completion (Estimated): January 28, 2027
• Study Completion (Estimated): January 28, 2027

Study Registration Dates

• First Submitted: December 1, 2020
• First Submitted That Met QC Criteria: December 1, 2020
• First Posted (Actual): December 8, 2020

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: May 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Diseases; Retinal Degeneration; Macular Degeneration; Wet Macular Degeneration; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Ranibizumab
• Other Study ID Numbers: WR42221; 2020-001313-20 (EudraCT Number); CIV-21-02-035827 (Other Identifier: EUDAMED NUMBER); 2023-507130-24-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes