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)

Neovascular Age-related Macular Degeneration (nAMD) Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04657289
• Other study ID #: WR42221
• Secondary ID: 2020-001313-20CI
• Status: Recruiting
• Phase: Phase 3
• Start date: July 14, 2021
• Est. completion date: December 31, 2026

Study information

• Verified date: May 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID Number: WR42221 https://forpatients.roche.com
• Phone: 888-662-6728 (U.S. and Canada)
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 442
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Macular Degeneration
• Neovascular Age-related Macular Degeneration (nAMD)
• Wet Macular Degeneration

Intervention

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

Locations

Country	Name	City	State
Argentina	Centro Oftalmológico Dr. Charles S.A.	Capital Federal
Argentina	Oftalmos	Capital Federal
Argentina	Grupo Laser Vision	Rosario
Australia	Eyeclinic Albury Wodonga	Albury	New South Wales
Australia	Centre For Eye Research Australia	East Melbourne	Victoria
Australia	Eye and Retina Consultants	Hurstville	New South Wales
Australia	Retina and Macula Specialists	Hurstville	New South Wales
Australia	Retina Associates Liverpool	Liverpool	New South Wales
Australia	The Lions Eye Institute	Nedlands	Western Australia
Australia	Retina Specialists Victoria	Rowville	Victoria
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
Austria	LKH-Univ.Klinikum Graz; Universitäts-Augenklinik	Graz
Austria	Medizinische Universität Wien; Universitätsklinik für Augenheilkunde und Optometrie	Wien
Belgium	CHU Brugmann (Victor Horta)	Bruxelles
Belgium	UZ Gent	Gent
Belgium	UZ Leuven Gasthuisberg	Leuven
Brazil	Instituto da Visão	Belo Horizonte	MG
Brazil	Botelho Hospital da Visao	Blumenau	SC
Brazil	Centro Brasileiro de Cirurgia	Goiania	GO
Brazil	Hospital da Gamboa - Instituto de Oftalmologia do Rio de Janeiro	Rio de Janeiro	RJ
Brazil	Clinica de Olhos Dr Abujamra	Sao Paulo	SP
Brazil	Instituto da Visão IPEPO	Sao Paulo	SP
Brazil	Retina Clinic	Sao Paulo	SP
Brazil	Universidade Federal de Sao Paulo - UNIFESP*X; Oftalmologia	Sao Paulo	SP
Brazil	Hosp de Olhos de Sorocaba	Sorocaba	SP
France	Hopital Pellegrin; Ophtalmologie	Bordeaux
France	Chi De Creteil; Ophtalmologie	Creteil
France	Hopital de la croix rousse; Ophtalmologie	Lyon cedex
France	CHNO des Quinze Vingts; Ophtalmologie	Paris
France	Hopital Lariboisiere; Ophtalmologie	Paris
France	Fondation Rothschild; Ophtalmologie	Paris Cedex 19
Germany	Städtisches Klinikum Dresden; Augenklinik	Dresden
Germany	Universitätsklinikum Freiburg, Klinik für Augenheilkunde	Freiburg
Germany	Universitätsklinikum Köln; Augenklinik	Köln
Germany	Klinikum der Stadt Ludwigshafen am Rhein gGmbH; Augenklinik	Ludwigshafen
Germany	LMU Klinikum der Universität, Augenklinik	München
Germany	Universitätsklinikum Münster; Augenheilkunde	Münster
Germany	Universitätsklinikum Regensburg, Klinik & Poliklinik für Augenheilkunde	Regensburg
Germany	Knappschaftsklinikum Saar GmbH; Augenklinik Sulzbach	Sulzbach
Germany	Universitätsklinikum Tübingen	Tübingen
Germany	Universitätsklinikum Ulm, Augenklinik und Poliklinik	Ulm
Israel	Rambam Medical Center; Opthalmology	Haifa
Israel	Hadassah MC; Ophtalmology	Jerusalem
Israel	Meir Medical Center; Ophtalmology	Kfar Saba
Israel	Rabin MC; Ophtalmology	Petach Tikva
Israel	Kaplan Medical Center; Ophtalmology	Rehovot
Israel	Tel Aviv Sourasky MC; Ophtalmology	Tel Aviv
Italy	Ospedale Clinicizzato SS Annunziata; Clinica Oftalmologica	Chieti	Abruzzo
Italy	Fondazione Irccs Ca' Granda Ospedale Maggiore Policlinico-Clinica Regina Elena;U.O.C Oculistica	Milano	Lombardia
Italy	Irccs Ospedale San Raffaele;U.O. Oculistica	Milano	Lombardia
Italy	Ospedale Classificato Equiparato Sacro Cuore ? Don Calabria; Dipartimento Oculistica	Negrar - Verona	Veneto
Italy	Policlinico Tor Vergata	Roma	Lazio
Italy	Policlinico Universitario Agostino Gemelli	Roma	Lazio
Italy	A.O. Universitaria S. Maria Della Misericordia Di Udine; Clinica Oculistica	Udine	Veneto
Korea, Republic of	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	Asan Medical Center	Seoul
Korea, Republic of	Kyung Hee University Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Singapore	Eye & Retina Surgeons	Singapore
Spain	Centro de Oftalmologia Barraquer; Servicio Oftalmologia	Barcelona
Spain	Hospital Clinic de Barcelona; Consultas Externas Oftalmologia	Barcelona
Spain	Hospital dos de maig; servicio de oftalmologia	Barcelona
Spain	Institut de la Macula i la retina	Barcelona
Spain	Oftalvist Valencia	Burjassot	Valencia
Spain	Hospital Universitario de Bellvitge	Hospitalet de Llobregat	Barcelona
Spain	Clinica Baviera; Servicio Oftalmologia	Madrid
Spain	Clinica Universitaria de Navarra; Servicio de Oftalmologia	Madrid
Spain	Hospital Universitario Puerta de Hierro	Majadahonda	Madrid
Spain	Clinica Universitaria de Navarra; Servicio de Oftalmologia	Pamplona	Navarra
Spain	Hospital General de Catalunya	San Cugat Del Valles	Barcelona
Spain	Hospital Universitario Rio Hortega; Servicio de Oftalmologia	Valladolid
Switzerland	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	Stadtspital Triemli Ophthalmologische Klinik	Zürich
Taiwan	Changhua Christian Hospital; Department of Ophthalmology	Changhua
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital; Ophthalmology	Kaohsiung
Taiwan	Taipei Veterans General Hospital; Ophthalmology	Taipei
Taiwan	Chang Gung Medical Foundation - Linkou; Ophthalmology	Taoyuan
Taiwan	National Taiwan University Hospital; Ophthalmology	Zhongzheng Dist.
Turkey	Ankara Ulucanlar Eye Research and Application Hospital; Ophthalmology	Ankara
Turkey	Kocaeli Üniversitesi T?p Fakültesi; Department of Ophthalmology	Kocaeli
United Kingdom	Bristol Eye Hospital;Retinal Treatment and Research Unit	Bristol
United Kingdom	Hull University Teaching Hospitals NHS Trust	Hull
United Kingdom	Royal Liverpool University Hospital	Liverpool
United Kingdom	Kings College Hospital	London
United Kingdom	Moorfields Eye Hospital NHS Foundation Trust	London
United Kingdom	Manchester University NHS Foundation Trust (MFT)	Manchester
United Kingdom	Royal Victoria Infirmary	Newcastle upon Tyne
United Kingdom	Sunderland Eye Infirmary	Sunderland
United Kingdom	New Cross Hospital	Wolverhampton

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

Argentina,  Australia,  Austria,  Belgium,  Brazil,  France,  Germany,  Israel,  Italy,  Korea, Republic of,  Singapore,  Spain,  Switzerland,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change from baseline in BCVA score over time		Baseline up to Week 72
Secondary	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
Secondary	Percentage of participants with BCVA score of 69 letters (approximate 20/40 Snellen equivalent) or better over time		Baseline up to Week 72
Secondary	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
Secondary	Percentage of participants with BCVA score of 38 letters (approximate 20/200 Snellen equivalent) or worse over time		Baseline up to Week 72
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Percentage of participants who lose <10, <5, or gain >= 0 letters in BCVA score from baseline over time		Baseline up to Week 72
Secondary	Incidence and severity of ocular and systemic (non-ocular) adverse events in the Q36W and Q24W arms		Baseline up to Week 72
Secondary	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
Secondary	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
Secondary	Incidence and severity of adverse device effects in the Q36W and Q24W arms		Baseline up to Week 72
Secondary	Incidence, causality, severity, and duration of anticipated serious adverse device effects in the Q36W and Q24W arms		Baseline up to Week 72
Secondary	Change from baseline in center point thickness (CPT) up to and including Week 72		Baseline up to Week 72
Secondary	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
Secondary	Observed serum concentration of ranibizumab at specified timepoints		Baseline to Week 72
Secondary	Incidence of treatment-emergent ADAs during the study		Baseline to Week 72