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)
- Conditions
- Neovascular Age-related Macular Degeneration (nAMD)
- Interventions
- Device: Port Delivery System with Ranibizumab
- Registration Number
- NCT04657289
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 442
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A [Q36W] 36-weeks between refill-exchange procedures Ranibizumab Participants randomized to the Q36W arm will receive PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) on a Q36W fixed interval. Arm A [Q36W] 36-weeks between refill-exchange procedures Port Delivery System with Ranibizumab Participants randomized to the Q36W arm will receive PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) on a Q36W fixed interval. Arm B [Q24W] 24-weeks between refill-exchange procedures Ranibizumab Participants randomized to the Q24W arm will receive PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) on a Q24W fixed interval. Arm B [Q24W] 24-weeks between refill-exchange procedures Port Delivery System with Ranibizumab Participants randomized to the Q24W arm will receive PDS implant refill-exchange procedures (ranibizumab 100 mg/mL) on a Q24W fixed interval.
- Primary Outcome Measures
Name Time Method 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 Baseline to Week 72 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.
- Secondary Outcome Measures
Name Time Method Change from baseline in center point thickness (CPT) up to and including Week 72 Baseline up to Week 72 Change from baseline in BCVA score over time 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, causality, severity, and duration of anticipated serious adverse device effects in the Q36W and Q24W arms 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 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 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 Incidence and severity of ocular and systemic (non-ocular) adverse events in the Q36W and Q24W arms 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 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 who lose <10, <5, or gain >= 0 letters in BCVA score from baseline over time Baseline up 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 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 Incidence and severity of adverse device effects in the Q36W and Q24W arms Baseline up to Week 72
Trial Locations
- Locations (122)
Rabin MC
🇮🇱Petach Tikva, Israel
Kaplan Medical Center
🇮🇱Rehovot, Israel
Tel Aviv Sourasky MC
🇮🇱Tel Aviv, Israel
Centre Rétine Gallien
🇫🇷Bordeaux, France
Chi De Creteil
🇫🇷Creteil, France
CHU Bocage
🇫🇷Dijon, France
Centro Oftalmológico Dr. Charles S.A.
🇦🇷Capital Federal, Argentina
Oftalmos
🇦🇷Capital Federal, Argentina
Grupo Laser Vision
🇦🇷Rosario, Argentina
Eyeclinic Albury Wodonga
🇦🇺Albury, New South Wales, Australia
Eye and Retina Consultants
🇦🇺Hurstville, New South Wales, Australia
Retina Associates Liverpool
🇦🇺Liverpool, New South Wales, Australia
Retina and Macula Specialists
🇦🇺Miranda, New South Wales, Australia
Sydney Eye Hospital
🇦🇺Sydney, New South Wales, Australia
Sydney Retina Clinic and Day Surgery
🇦🇺Sydney, New South Wales, Australia
Queensland Eye Institute
🇦🇺Woolloongabba, Queensland, Australia
Centre For Eye Research Australia
🇦🇺East Melbourne, Victoria, Australia
Retina Specialists Victoria
🇦🇺Rowville, Victoria, Australia
The Lions Eye Institute
🇦🇺Nedlands, Western Australia, Australia
LKH-Univ.Klinikum Graz
🇦🇹Graz, Austria
Medizinische Universität Wien
🇦🇹Wien, Austria
CHU Brugmann (Victor Horta)
🇧🇪Bruxelles, Belgium
UZ Gent
🇧🇪Gent, Belgium
UZ Leuven Gasthuisberg
🇧🇪Leuven, Belgium
Hospital das Clinicas - UFRGS
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Botelho Hospital da Visao
🇧🇷Blumenau, Santa Catarina, Brazil
Retina Clinic
🇧🇷Sao Paulo, São Paulo, Brazil
Universidade Federal de Sao Paulo - UNIFESP*X
🇧🇷Sao Paulo, São Paulo, Brazil
Instituto da Visão IPEPO
🇧🇷Sao Paulo, São Paulo, Brazil
Hosp de Olhos de Sorocaba
🇧🇷Sorocaba, São Paulo, Brazil
Hopital de la croix rousse
🇫🇷Lyon cedex, France
Centre Paradis Monticelli
🇫🇷Marseille, France
CHU Nantes - Hôtel Dieu
🇫🇷Nantes, France
CHU de Nice Hopital Pasteur
🇫🇷Nice, France
Fondation Rothschild
🇫🇷Paris Cedex 19, France
Hopital Lariboisiere
🇫🇷Paris, France
Hôpital PURPAN - CHU TOULOUSE
🇫🇷Toulouse, France
Universitatsklinikum Bonn
🇩🇪Bonn, Germany
Medizinische Universität Lausitz ? Carl Thiem
🇩🇪Cottbus, Germany
Augenzentrum Prof. Koch GmbH
🇩🇪Frankfurt, Germany
Universitätsklinikum Freiburg, Klinik für Augenheilkunde
🇩🇪Freiburg, Germany
Universitätsklinikum Hamburg-Eppendorf
🇩🇪Hamburg, Germany
Universitätsklinikum Köln
🇩🇪Köln, Germany
Klinikum der Stadt Ludwigshafen am Rhein gGmbH
🇩🇪Ludwigshafen, Germany
LMU Klinikum der Universität, Augenklinik
🇩🇪München, Germany
Augenabteilung am St. Franziskus-Hospital
🇩🇪Münster, Germany
Universitätsklinikum Münster
🇩🇪Münster, Germany
Universitätsklinikum Regensburg, Klinik & Poliklinik für Augenheilkunde
🇩🇪Regensburg, Germany
Knappschaftsklinikum Saar GmbH
🇩🇪Sulzbach, Germany
Universitätsklinikum Tübingen
🇩🇪Tuebingen, Germany
Universitätsklinikum Ulm, Augenklinik und Poliklinik
🇩🇪Ulm, Germany
Rambam Medical Center
🇮🇱Haifa, Israel
Hadassah MC
🇮🇱Jerusalem, Israel
Meir Medical Center
🇮🇱Kfar Saba, Israel
Ospedale Clinicizzato SS Annunziata
🇮🇹Chieti, Abruzzo, Italy
Azienda Ospedaliero Universitaria "Ospedali Riuniti" Trieste-Ospedale Maggiore
🇮🇹Trieste, Friuli-Venezia Giulia, Italy
Policlinico Tor Vergata
🇮🇹Roma, Lazio, Italy
Policlinico Universitario Agostino Gemelli
🇮🇹Roma, Lazio, Italy
Fondazione G.B. Bietti Per Lo Studio E La Ricerca in Oftalmologia-Presidio Ospedaliero Britannico
🇮🇹Roma, Lazio, Italy
Fondazione Irccs Ca' Granda Ospedale Maggiore Policlinico-Clinica Regina Elena
🇮🇹Milano, Lombardia, Italy
Irccs Ospedale San Raffaele
🇮🇹Milano, Lombardia, Italy
Asst Fatebenefratelli Sacco
🇮🇹Milano, Lombardia, Italy
Azienda Ospedaliero Universitaria Ospedali Riuniti
🇮🇹Torrette - Ancona, Marche, Italy
AOU Città della Salute e della Scienza di Torino
🇮🇹Torino, Piemonte, Italy
Policlinico di Bari
🇮🇹Bari, Puglia, Italy
Azienda Ospedaliero-Universitaria Careggi
🇮🇹Firenze, Toscana, Italy
Azienda Ospedaliera di Perugia Ospedale S. Maria Della Misericordia
🇮🇹Perugia, Umbria, Italy
Ospedale Classificato Equiparato Sacro Cuore ? Don Calabria
🇮🇹Negrar - Verona, Veneto, Italy
A.O. Universitaria S. Maria Della Misericordia Di Udine
🇮🇹Udine, Veneto, Italy
Pusan National University Hospital
🇰🇷Busan, Korea, Republic of
Yeungnam University Medical Center
🇰🇷Daegu, Korea, Republic of
Gachon University Gil Medical Center
🇰🇷Incheon, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Korea, Republic of
Kyung Hee University Hospital
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Kim's Eye Hospital
🇰🇷Seoul, Korea, Republic of
National University Hospital
🇸🇬Singapore, Singapore
Singapore Eye Research Institute
🇸🇬Singapore, Singapore
Eye & Retina Surgeons
🇸🇬Singapore, Singapore
Tan Tock Seng Hospital
🇸🇬Singapore, Singapore
Instituto Oftalmologico Fernandez Vega
🇪🇸Oviedo, Asturias, Spain
Hospital Universitario de Bellvitge
🇪🇸Hospitalet de Llobregat, Barcelona, Spain
Hospital General de Catalunya
🇪🇸San Cugat Del Valles, Barcelona, Spain
Hospital Universitario Puerta de Hierro
🇪🇸Majadahonda, Madrid, Spain
Clinica Universitaria de Navarra
🇪🇸Madrid, Spain
Centro de Oftalmologia Barraquer
🇪🇸Barcelona, Spain
Institut de la Macula i la retina
🇪🇸Barcelona, Spain
Hospital dos de maig
🇪🇸Barcelona, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital de la Arruzafa. Servicio de Oftalmologia
🇪🇸Cordoba, Spain
Clinica Baviera
🇪🇸Madrid, Spain
Oftalvist Valencia
🇪🇸Valencia, Spain
Hospital Universitario Rio Hortega
🇪🇸Valladolid, Spain
Universitätsspital Basel Augenklinik Klinik
🇨🇭Basel, Switzerland
Inselspital Bern Ophthalmologische Klinik
🇨🇭Bern, Switzerland
Vista Klinik Ophthalmologische Klinik
🇨🇭Binningen, Switzerland
Fondation Asile Des Aveugles ? Jules Gonin Eye Hospital
🇨🇭Lausanne, Switzerland
Luzerner Kantonsspital LUKS
🇨🇭Luzern 16, Switzerland
Stadtspital Triemli Ophthalmologische Klinik
🇨🇭Zürich, Switzerland
Changhua Christian Hospital
🇨🇳Changhua, Taiwan
Kaohsiung Medical University Chung-Ho Memorial Hospital
🇨🇳Kaohsiung, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Chang Gung Medical Foundation - Linkou
🇨🇳Taoyuan, Taiwan
National Taiwan University Hospital
🇨🇳Zhongzheng Dist., Taiwan
Hacettepe University Medical Faculty
🇹🇷Ankara, Turkey
Ankara Bilkent City Hospital
🇹🇷Ankara, Turkey
Ankara Etlik City Hospital
🇹🇷Ankara, Turkey
Beyoglu Goz Training and Research Hospital
🇹🇷Istanbul, Turkey
Kocaeli Üniversitesi T?p Fakültesi
🇹🇷Kocaeli, Turkey
Bristol Eye Hospital
🇬🇧Bristol, United Kingdom
Hull University Teaching Hospitals NHS Trust
🇬🇧Hull, United Kingdom
Royal Liverpool University Hospital
🇬🇧Liverpool, United Kingdom
Moorfields Eye Hospital NHS Foundation Trust
🇬🇧London, United Kingdom
Central Middlesex Hospital
🇬🇧London, United Kingdom
Kings College Hospital
🇬🇧London, United Kingdom
Royal Victoria Infirmary
🇬🇧Newcastle upon Tyne, United Kingdom
University Hospital Southampton NHS Foundation Trust
🇬🇧Southampton, United Kingdom
Sunderland Eye Infirmary
🇬🇧Sunderland, United Kingdom
New Cross Hospital
🇬🇧Wolverhampton, United Kingdom