Clinical trial NCT04657289: 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)
Official title: 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 type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Neovascular Age-related Macular Degeneration (nAMD)
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2020-12-08
Enrollment: 442
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase 3b
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Baseline to Week 72
Secondary outcomes:
measure: Change from baseline in BCVA score over time
timeFrame: Baseline up to Week 72
measure: Percentage of participants with BCVA score of 69 letters (approximate 20/40 Snellen equivalent) or better averaged over Weeks 68 and 72
timeFrame: Baseline to Week 72
measure: Percentage of participants with BCVA score of 69 letters (approximate 20/40 Snellen equivalent) or better over time
timeFrame: Baseline up to Week 72
measure: Percentage of participants with BCVA score of 38 letters (approximate 20/200 Snellen equivalent) or worse averaged over Weeks 68 and 72
timeFrame: Baseline to Week 72
measure: Percentage of participants with BCVA score of 38 letters (approximate 20/200 Snellen equivalent) or worse over time
timeFrame: Baseline up to Week 72
measure: 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
timeFrame: At Weeks 24, 40, 72
measure: 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
timeFrame: At Weeks 24, 40, 72
measure: 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
timeFrame: At Week 40
measure: Percentage of participants who lose <10, <5, or gain >= 0 letters in BCVA score from baseline averaged over Weeks 68 and 72
timeFrame: Baseline to Week 72
measure: Percentage of participants who lose <10, <5, or gain >= 0 letters in BCVA score from baseline over time
timeFrame: Baseline up to Week 72
measure: Incidence and severity of ocular and systemic (non-ocular) adverse events in the Q36W and Q24W arms
timeFrame: Baseline up to Week 72
measure: Incidence, severity, and duration of adverse events of special interest, including ocular adverse events of special interest in the Q36W and Q24W arms
timeFrame: Baseline up to Week 72
measure: 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
timeFrame: Baseline up to Week 72
measure: Incidence and severity of adverse device effects in the Q36W and Q24W arms
timeFrame: Baseline up to Week 72
measure: Incidence, causality, severity, and duration of anticipated serious adverse device effects in the Q36W and Q24W arms
timeFrame: Baseline up to Week 72
measure: Change from baseline in center point thickness (CPT) up to and including Week 72
timeFrame: Baseline up to Week 72
measure: Percentage of participants who do not undergo supplemental treatment with intravitreal ranibizumab 0.5 mg before each refill-exchange procedure
timeFrame: Week 16 to Week 68
measure: Observed serum concentration of ranibizumab at specified timepoints
timeFrame: Baseline to Week 72
measure: Incidence of treatment-emergent ADAs during the study
timeFrame: Baseline to Week 72
Other outcomes:
Locations:
city: Capital Federal
country: Argentina
facility: Centro Oftalmológico Dr. Charles S.A.
city: Capital Federal
country: Argentina
facility: Oftalmos
city: Rosario
country: Argentina
facility: Grupo Laser Vision
city: Albury
country: Australia
facility: Eyeclinic Albury Wodonga
state: New South Wales
city: Hurstville
country: Australia
facility: Eye and Retina Consultants
state: New South Wales
city: Liverpool
country: Australia
facility: Retina Associates Liverpool
state: New South Wales
city: Miranda
country: Australia
facility: Retina and Macula Specialists
state: New South Wales
city: Sydney
country: Australia
facility: Sydney Eye Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Sydney Retina Clinic and Day Surgery
state: New South Wales
city: Woolloongabba
country: Australia
facility: Queensland Eye Institute
state: Queensland
city: East Melbourne
country: Australia
facility: Centre For Eye Research Australia
state: Victoria
city: Rowville
country: Australia
facility: Retina Specialists Victoria
state: Victoria
city: Nedlands
country: Australia
facility: The Lions Eye Institute
state: Western Australia
city: Graz
country: Austria
facility: LKH-Univ.Klinikum Graz
city: Wien
country: Austria
facility: Medizinische Universität Wien
city: Bruxelles
country: Belgium
facility: CHU Brugmann (Victor Horta)
city: Gent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg
city: Porto Alegre
country: Brazil
facility: Hospital das Clinicas - UFRGS
state: Rio Grande Do Sul
city: Blumenau
country: Brazil
facility: Botelho Hospital da Visao
state: Santa Catarina
city: Sao Paulo
country: Brazil
facility: Retina Clinic
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Universidade Federal de Sao Paulo - UNIFESP*X
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Instituto da Visão IPEPO
state: São Paulo
city: Sorocaba
country: Brazil
facility: Hosp de Olhos de Sorocaba
state: São Paulo
city: Bordeaux
country: France
facility: Centre Rétine Gallien
city: Creteil
country: France
facility: Chi De Creteil
city: Dijon
country: France
facility: CHU Bocage
city: Lyon cedex
country: France
facility: Hopital de la croix rousse
city: Marseille
country: France
facility: Centre Paradis Monticelli
city: Nantes
country: France
facility: CHU Nantes - Hôtel Dieu
city: Nice
country: France
facility: CHU de Nice Hopital Pasteur
city: Paris Cedex 19
country: France
facility: Fondation Rothschild
city: Paris
country: France
facility: Hopital Lariboisiere
city: Toulouse
country: France
facility: Hôpital PURPAN - CHU TOULOUSE
city: Bonn
country: Germany
facility: Universitatsklinikum Bonn
city: Cottbus
country: Germany
facility: Medizinische Universität Lausitz ? Carl Thiem
city: Frankfurt
country: Germany
facility: Augenzentrum Prof. Koch GmbH
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg, Klinik für Augenheilkunde
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Köln
country: Germany
facility: Universitätsklinikum Köln
city: Ludwigshafen
country: Germany
facility: Klinikum der Stadt Ludwigshafen am Rhein gGmbH
city: München
country: Germany
facility: LMU Klinikum der Universität, Augenklinik
city: Münster
country: Germany
facility: Augenabteilung am St. Franziskus-Hospital
city: Münster
country: Germany
facility: Universitätsklinikum Münster
city: Regensburg
country: Germany
facility: Universitätsklinikum Regensburg, Klinik & Poliklinik für Augenheilkunde
city: Sulzbach
country: Germany
facility: Knappschaftsklinikum Saar GmbH
city: Tuebingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm, Augenklinik und Poliklinik
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Jerusalem
country: Israel
facility: Hadassah MC
city: Kfar Saba
country: Israel
facility: Meir Medical Center
city: Petach Tikva
country: Israel
facility: Rabin MC
city: Rehovot
country: Israel
facility: Kaplan Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky MC
city: Chieti
country: Italy
facility: Ospedale Clinicizzato SS Annunziata
state: Abruzzo
city: Trieste
country: Italy
facility: Azienda Ospedaliero Universitaria "Ospedali Riuniti" Trieste-Ospedale Maggiore
state: Friuli-Venezia Giulia
city: Roma
country: Italy
facility: Policlinico Tor Vergata
state: Lazio
city: Roma
country: Italy
facility: Policlinico Universitario Agostino Gemelli
state: Lazio
city: Roma
country: Italy
facility: Fondazione G.B. Bietti Per Lo Studio E La Ricerca in Oftalmologia-Presidio Ospedaliero Britannico
state: Lazio
city: Milano
country: Italy
facility: Fondazione Irccs Ca' Granda Ospedale Maggiore Policlinico-Clinica Regina Elena
state: Lombardia
city: Milano
country: Italy
facility: Irccs Ospedale San Raffaele
state: Lombardia
city: Milano
country: Italy
facility: Asst Fatebenefratelli Sacco
state: Lombardia
city: Torrette - Ancona
country: Italy
facility: Azienda Ospedaliero Universitaria Ospedali Riuniti
state: Marche
city: Torino
country: Italy
facility: AOU Città della Salute e della Scienza di Torino
state: Piemonte
city: Bari
country: Italy
facility: Policlinico di Bari
state: Puglia
city: Firenze
country: Italy
facility: Azienda Ospedaliero-Universitaria Careggi
state: Toscana
city: Perugia
country: Italy
facility: Azienda Ospedaliera di Perugia Ospedale S. Maria Della Misericordia
state: Umbria
city: Negrar - Verona
country: Italy
facility: Ospedale Classificato Equiparato Sacro Cuore ? Don Calabria
state: Veneto
city: Udine
country: Italy
facility: A.O. Universitaria S. Maria Della Misericordia Di Udine
state: Veneto
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Daegu
country: Korea, Republic of
facility: Yeungnam University Medical Center
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Kyung Hee University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Kim's Eye Hospital
city: Singapore
country: Singapore
facility: National University Hospital
city: Singapore
country: Singapore
facility: Singapore Eye Research Institute
city: Singapore
country: Singapore
facility: Eye & Retina Surgeons
city: Singapore
country: Singapore
facility: Tan Tock Seng Hospital
city: Oviedo
country: Spain
facility: Instituto Oftalmologico Fernandez Vega
state: Asturias
city: Hospitalet de Llobregat
country: Spain
facility: Hospital Universitario de Bellvitge
state: Barcelona
city: San Cugat Del Valles
country: Spain
facility: Hospital General de Catalunya
state: Barcelona
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro
state: Madrid
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra
state: Navarra
city: Barcelona
country: Spain
facility: Centro de Oftalmologia Barraquer
city: Barcelona
country: Spain
facility: Institut de la Macula i la retina
city: Barcelona
country: Spain
facility: Hospital dos de maig
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Cordoba
country: Spain
facility: Hospital de la Arruzafa. Servicio de Oftalmologia
city: Madrid
country: Spain
facility: Clinica Universitaria de Navarra
city: Madrid
country: Spain
facility: Clinica Baviera
city: Valencia
country: Spain
facility: Oftalvist Valencia
city: Valladolid
country: Spain
facility: Hospital Universitario Rio Hortega
city: Basel
country: Switzerland
facility: Universitätsspital Basel Augenklinik Klinik
city: Bern
country: Switzerland
facility: Inselspital Bern Ophthalmologische Klinik
city: Binningen
country: Switzerland
facility: Vista Klinik Ophthalmologische Klinik
city: Lausanne
country: Switzerland
facility: Fondation Asile Des Aveugles ? Jules Gonin Eye Hospital
city: Luzern 16
country: Switzerland
facility: Luzerner Kantonsspital LUKS
city: Zürich
country: Switzerland
facility: Stadtspital Triemli Ophthalmologische Klinik
city: Changhua
country: Taiwan
facility: Changhua Christian Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Medical Foundation - Linkou
city: Zhongzheng Dist.
country: Taiwan
facility: National Taiwan University Hospital
city: Ankara
country: Turkey
facility: Hacettepe University Medical Faculty
city: Ankara
country: Turkey
facility: Ankara Bilkent City Hospital
city: Ankara
country: Turkey
facility: Ankara Etlik City Hospital
city: Istanbul
country: Turkey
facility: Beyoglu Goz Training and Research Hospital
city: Kocaeli
country: Turkey
facility: Kocaeli Üniversitesi T?p Fakültesi
city: Bristol
country: United Kingdom
facility: Bristol Eye Hospital
city: Hull
country: United Kingdom
facility: Hull University Teaching Hospitals NHS Trust
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital
city: London
country: United Kingdom
facility: Moorfields Eye Hospital NHS Foundation Trust
city: London
country: United Kingdom
facility: Central Middlesex Hospital
city: London
country: United Kingdom
facility: Kings College Hospital
city: Newcastle upon Tyne
country: United Kingdom
facility: Royal Victoria Infirmary
city: Southampton
country: United Kingdom
facility: University Hospital Southampton NHS Foundation Trust
city: Sunderland
country: United Kingdom
facility: Sunderland Eye Infirmary
city: Wolverhampton
country: United Kingdom
facility: New Cross Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: