Extension Study for the Port Delivery System With Ranibizumab (Portal) (Portal)

A Multicenter, Open-Label Extension Study to Evaluate the Long-Term Safety and Tolerability of the Port Delivery System With Ranibizumab in Patients With Neovascular Age-Related Macular Degeneration (Portal)

This study will evaluate the long-term safety and tolerability of the Port Delivery System with ranibizumab (PDS) (100 mg/mL) in participants with neovascular age-related macular degeneration (nAMD) who have either completed Phase II Study GX28228 (Ladder), Phase III Study GR40548 (Archway), Phase IIIb Study WR42221 (Velodrome), or completed Week 24 visit in Study WR42221 but were not eligible to be randomized in WR42221.

Study Overview

• Status: Recruiting
• Conditions: Neovascular Age-Related Macular Degeneration
• Intervention / Treatment: Drug: PDS Implant with Ranibizumab 100 mg/mL

Detailed Description

The Transscleral Photocoagulation sub-study (sub-study 1) will evaluate the effectiveness of using transscleral photocoagulation (TPC) with the Iridex laser system to mitigate vitreous hemorrhages secondary to the Port Delivery System with ranibizumab (PDS) implantation procedure in participants with neovascular age-related macular degeneration (nAMD). The sub-study will enroll about 55 participants.

The Re-implantation sub-study (sub-study 2) will evaluate the safety of re-implantation with the updated PDS with ranibizumab . Up to 100 participants who previously participated in the main study in the United States will be enrolled and followed for a maximum of 72 weeks post-re-implantation in the substudy.

• Study Type: Interventional
• Enrollment (Estimated): 1000
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: GR40549 https://forpatients.roche.com/; Phone Number: 888-662-6728 (U.S. and Canada); Email: global-roche-genentech-trials@gene.com
• Study Contact Backup: Name: Fastest response: use the inquiry form. No email attachments. https://www.gene.com/contact-us/submit-medical-inquiry

Study Locations

• Argentina
  • Capital Federal, Argentina, C1120AAN
    • Recruiting
    • Oftalmos
  • Ciudad Autonoma Buenos Aires, Argentina, C1121ABB
    • Recruiting
    • Centro Oftalmologico Dr. Charles S.A.
  • Rosario, Argentina, S2000DLA
    • Recruiting
    • Grupo Laser Vision
• Australia
  • New South Wales
    • Albury, New South Wales, Australia, 2640
      • Active, not recruiting
      • Eyeclinic Albury Wodonga
    • Hurstville, New South Wales, Australia, 2220
      • Recruiting
      • Eye and Retina Consultants
• Austria
  • Graz, Austria, 8036
    • Recruiting
    • LKH-Univ.Klinikum Graz
  • Vienna, Austria, 1090
    • Recruiting
    • Medizinische Universitat Wien
• Belgium
  • Leuven, Belgium, 3000
    • Withdrawn
    • UZ Leuven Gasthuisberg
• Brazil
  • Santa Catarina
    • Blumenau, Santa Catarina, Brazil, 89052-504
      • Recruiting
      • Botelho Hospital da Visao
  • São Paulo
    • Sorocaba, São Paulo, Brazil, 18031-060
      • Recruiting
      • Hosp de Olhos de Sorocaba
    • São Paulo, São Paulo, Brazil, 01427-002
      • Recruiting
      • Retina Clinic
    • São Paulo, São Paulo, Brazil, 04038-032
      • Recruiting
      • Instituto da Visao IPEPO
    • São Paulo, São Paulo, Brazil, 04023-062
      • Recruiting
      • Universidade Federal de Sao Paulo - UNIFESPX
• France
  • Bordeaux, France, 33000
    • Recruiting
    • Centre Rétine Gallien
  • Lyon, France, 69317
    • Recruiting
    • Hopital de la croix rousse
  • Marseille, France, 13008
    • Recruiting
    • Centre Paradis Monticelli
  • Paris, France, 75010
    • Recruiting
    • Hôpital Lariboisière
  • Paris, France, 75940
    • Recruiting
    • Fondation Rothschild
• Germany
  • Bonn, Germany, 53127
    • Recruiting
    • Universitatsklinikum Bonn
  • Cologne, Germany, 50937
    • Recruiting
    • Universitatsklinikum Koln
  • Cottbus, Germany, 03048
    • Recruiting
    • Medizinische Universitat Lausitz ? Carl Thiem
  • Freiburg im Breisgau, Germany, 79106
    • Recruiting
    • Universitätsklinikum Freiburg, Klinik für Augenheilkunde
  • Hamburg, Germany, 20246
    • Recruiting
    • Universitätsklinikum Hamburg-Eppendorf
  • Ludwigshafen, Germany, 67063
    • Recruiting
    • Klinikum der Stadt Ludwigshafen am Rhein gGmbH
  • München, Germany, 80336
    • Recruiting
    • LMU Klinikum der Universitat, Augenklinik
  • Münster, Germany, 48149
    • Recruiting
    • Universitätsklinikum Münster
  • Münster, Germany, 48145
    • Recruiting
    • Augenabteilung am St. Franziskus-Hospital
  • Sulzbach, Germany, 66280
    • Recruiting
    • Knappschaftsklinikum Saar GmbH
  • Tübingen, Germany, 72076
    • Recruiting
    • Universitätsklinikum Tübingen
  • Ulm, Germany, 89075
    • Recruiting
    • Universitatsklinikum Ulm, Augenklinik und Poliklinik
• Israel
  • Haifa, Israel, 3109601
    • Recruiting
    • Rambam Medical Center
  • Jerusalem, Israel, 9112001
    • Recruiting
    • Hadassah MC
  • Kfar Saba, Israel, 4428164
    • Recruiting
    • Meir Medical Center
  • Petah Tikva, Israel, 4941492
    • Recruiting
    • Rabin MC
  • Rehovot, Israel, 7660101
    • Recruiting
    • Kaplan Medical Center
  • Tel Aviv, Israel, 6423906
    • Recruiting
    • Tel Aviv Sourasky MC
• Italy
  • Abruzzo
    • Chieti, Abruzzo, Italy, 66100
      • Recruiting
      • Ospedale Clinicizzato SS Annunziata
  • Apulia
    • Bari, Apulia, Italy, 70124
      • Recruiting
      • Policlinico di Bari
  • Friuli Venezia Giulia
    • Trieste, Friuli Venezia Giulia, Italy, 34129
      • Recruiting
      • Azienda Ospedaliero Universitaria "Ospedali Riuniti" Trieste-Ospedale Maggiore
  • Lazio
    • Rome, Lazio, Italy, 00168
      • Recruiting
      • Policlinico Universitario Agostino Gemelli
    • Rome, Lazio, Italy, 00198
      • Recruiting
      • Fondazione G.B. Bietti Per Lo Studio E La Ricerca in Oftalmologia-Presidio Ospedaliero Britannico
  • Lombardy
    • Milan, Lombardy, Italy, 20157
      • Recruiting
      • ASST Fatebenefratelli Sacco
    • Milan, Lombardy, Italy, 20132
      • Recruiting
      • IRCCS Ospedale San Raffaele
    • Milan, Lombardy, Italy, 20100
      • Recruiting
      • Fondazione Irccs Ca' Granda Ospedale Maggiore Policlinico-Clinica Regina Elena
  • The Marches
    • Torrette - Ancona, The Marches, Italy, 60126
      • Recruiting
      • Azienda Ospedaliero Universitaria Ospedali Riuniti
  • Tuscany
    • Florence, Tuscany, Italy, 50134
      • Recruiting
      • Azienda Ospedaliero-Universitaria Careggi
  • Umbria
    • Perugia, Umbria, Italy, 06129
      • Recruiting
      • Azienda Ospedaliera di Perugia Ospedale S. Maria Della Misericordia
  • Veneto
    • Negrar - Verona, Veneto, Italy, 37024
      • Recruiting
      • Ospedale Classificato Equiparato Sacro Cuore ? Don Calabria
    • Udine, Veneto, Italy, 33100
      • Recruiting
      • A.O. Universitaria S. Maria Della Misericordia Di Udine
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08022
    • Recruiting
    • Institut de la Macula i la retina
  • Barcelona, Spain, 08025
    • Completed
    • Hospital Dos de Maig
  • Barcelona, Spain, 08021
    • Recruiting
    • Centro de Oftalmologia Barraquer
  • Córdoba, Spain, 14012
    • Recruiting
    • Hospital de la Arruzafa. Servicio de Oftalmologia
  • Madrid, Spain, 28046
    • Recruiting
    • Clinica Baviera
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Recruiting
      • Hospital Universitario de Bellvitge
    • San Cugat Del Valles, Barcelona, Spain, 08195
      • Recruiting
      • Hospital General de Catalunya
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Recruiting
      • Hospital Universitario Puerta de Hierro
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Recruiting
      • Clinica Universitaria de Navarra
  • Principality of Asturias
    • Oviedo, Principality of Asturias, Spain, 33012
      • Recruiting
      • Instituto Oftalmologico Fernandez Vega
  • Valencia
    • Burjassot, Valencia, Spain, 46100
      • Recruiting
      • Oftalvist Valencia
• Switzerland
  • Basel, Switzerland, 4056
    • Recruiting
    • Universitatsspital Basel Augenklinik Klinik
  • Bern, Switzerland, 3010
    • Recruiting
    • Inselspital Bern Ophthalmologische Klinik
  • Binningen, Switzerland, 4102
    • Active, not recruiting
    • Vista Klinik Ophthalmologische Klinik
  • Lausanne, Switzerland
    • Recruiting
    • Fondation Asile Des Aveugles ? Jules Gonin Eye Hospital
  • Zurich, Switzerland, 8063
    • Active, not recruiting
    • Stadtspital Triemli Ophthalmologische Klinik
• Taiwan
  • Changhua, Taiwan, 500
    • Recruiting
    • Changhua Christian Hospital
  • Kaohsiung City, Taiwan
    • Recruiting
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Taipei, Taiwan, 11217
    • Recruiting
    • Taipei Veterans General Hospital
  • Taoyuan, Taiwan, 333
    • Recruiting
    • Chang Gung Medical Foundation - Linkou
  • Zhongzheng Dist., Taiwan, 10002
    • Recruiting
    • National Taiwan University Hospital
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06100
    • Recruiting
    • Hacettepe University Medical Faculty
  • Ankara, Turkey (Türkiye), 06490
    • Recruiting
    • Ankara Bilkent City Hospital
  • Ankara, Turkey (Türkiye), DUMMY_VALUE
    • Recruiting
    • Ankara Etlik City Hospital
  • Istanbul, Turkey (Türkiye), 34421
    • Recruiting
    • Beyoglu Goz Training and Research Hospital
  • Kocaeli, Turkey (Türkiye), 41380
    • Recruiting
    • Kocaeli University Medical Faculty
• United Kingdom
  • Bristol, United Kingdom, BS1 2LX
    • Recruiting
    • Bristol Eye Hospital
  • Liverpool, United Kingdom, L7 8XP
    • Active, not recruiting
    • Royal Liverpool University Hospital
  • London, United Kingdom, NW10 7NS
    • Recruiting
    • Central Middlesex Hospital
  • London, United Kingdom, EC1V 2PD
    • Active, not recruiting
    • Moorfields Eye Hospital NHS Foundation Trust
  • London, United Kingdom, SE5 9RS
    • Active, not recruiting
    • Kings College Hospital NHS Foundation Trust
  • Newcastle upon Tyne, United Kingdom, NE1 4LP
    • Recruiting
    • Royal Victoria Infirmary
  • Sunderland, United Kingdom, SR2 9HP
    • Recruiting
    • Sunderland Eye Infirmary
  • Wolverhampton, United Kingdom, WV10 0QP
    • Recruiting
    • Royal Wolverhampton hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85014
      • Completed
      • Retinal Research Institute, LLC
    • Phoenix, Arizona, United States, 85016
      • Active, not recruiting
      • Barnet Dulaney Perkins Eye Center
    • Phoenix, Arizona, United States, 85020
      • Completed
      • Associated Retina Consultants
    • Phoenix, Arizona, United States, 85053
      • Completed
      • Retinal Consultants of Arizona
    • Phoenix, Arizona, United States, 85016
      • Completed
      • Arizona Retina and Vitreous Consultants
  • California
    • Bakersfield, California, United States, 93309
      • Completed
      • California Retina Consultants
    • Beverly Hills, California, United States, 90211
      • Completed
      • Retina-Vitreous Associates Medical Group
    • Encino, California, United States, 91436
      • Active, not recruiting
      • The Retina Partners
    • La Jolla, California, United States, 92037
      • Completed
      • Jacobs Retina center at the Shiley eye Institute UCSD
    • Los Angeles, California, United States, 90095-7000
      • Completed
      • Jules Stein Eye Institute/ UCLA
    • Mountain View, California, United States, 94040
      • Completed
      • N CA Retina Vitreous Assoc
    • Poway, California, United States, 92064
      • Completed
      • Retina Consultants, San Diego
    • Sacramento, California, United States, 95841
      • Completed
      • Retinal Consultants Med Group
    • San Francisco, California, United States, 94109
      • Completed
      • West Coast Retina Medical Group
    • San Francisco, California, United States, 94158
      • Completed
      • UCSF
    • Santa Ana, California, United States, 92705
      • Completed
      • Orange County Retina Med Group
    • Santa Barbara, California, United States, 93103
      • Completed
      • California Retina Consultants
  • Colorado
    • Durango, Colorado, United States, 81303
      • Completed
      • Southwest Retina Consultants
    • Fort Collins, Colorado, United States, 80528
      • Completed
      • Eye Center of Northern CO
    • Lakewood, Colorado, United States, 80228
      • Completed
      • Colorado Retina Associates, PC
  • Connecticut
    • Waterford, Connecticut, United States, 06385
      • Completed
      • Retina Group of New England
  • Florida
    • Boynton Beach, Florida, United States, 33426
      • Completed
      • Florida Eye Microsurgical Inst
    • Fort Myers, Florida, United States, 33912
      • Completed
      • National Ophthalmic Research Institute
    • Melbourne, Florida, United States, 32901
      • Completed
      • Florida Eye Associates
    • Palm Beach Gardens, Florida, United States, 33410
      • Completed
      • Retina Care Specialists
    • Pensacola, Florida, United States, 32503
      • Completed
      • Retina Specialty Institute
    • Plantation, Florida, United States, 33324
      • Completed
      • Fort Lauderdale Eye Institute
    • St. Petersburg, Florida, United States, 33711
      • Active, not recruiting
      • Retina Vitreous Assoc of FL
    • Tallahassee, Florida, United States, 32308
      • Active, not recruiting
      • Southern Vitreoretinal Assoc
    • Tampa, Florida, United States, 33609
      • Completed
      • Retina Associates of Florida, LLC
  • Georgia
    • Augusta, Georgia, United States, 30909
      • Completed
      • Southeast Retina Center
    • Marietta, Georgia, United States, 30060
      • Withdrawn
      • Georgia Retina PC
  • Illinois
    • Joliet, Illinois, United States, 60435
      • Completed
      • Illinois Retina Associates
    • Oak Forest, Illinois, United States, 60452
      • Completed
      • University Retina and Macula Associates, PC
  • Iowa
    • West Des Moines, Iowa, United States, 50266
      • Completed
      • Wolfe Eye Clinic
  • Kansas
    • Lenexa, Kansas, United States, 66215
      • Completed
      • Retina Associates
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • Completed
      • Retina Associates of Kentucky
    • Paducah, Kentucky, United States, 42001
      • Withdrawn
      • Paducah Retinal Center
  • Maine
    • Portland, Maine, United States, 04101
      • Completed
      • Maine Eye Center
  • Maryland
    • Baltimore, Maryland, United States, 21209
      • Completed
      • The Retina Care Center
    • Baltimore, Maryland, United States, 21287
      • Active, not recruiting
      • Johns Hopkins Med
    • Chevy Chase, Maryland, United States, 20815
      • Completed
      • Retina Group of Washington
    • Towson, Maryland, United States, 21204
      • Completed
      • Retina Specialists
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Completed
      • Ophthalmic Consultants of Boston
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Completed
      • Foundation for Vision Research
    • Royal Oak, Michigan, United States, 48073
      • Completed
      • Associated Retinal Consultants
  • Minnesota
    • Minneapolis, Minnesota, United States, 55435
      • Completed
      • VitreoRetinal Surgery, PLLC.
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • Completed
      • Midwest Vision Research Foundation
    • St Louis, Missouri, United States, 63128
      • Completed
      • The Retina Institute - Chesterfield
  • Nevada
    • Reno, Nevada, United States, 89502
      • Completed
      • Sierra Eye Associates
  • New Jersey
    • Bloomfield, New Jersey, United States, 07003
      • Completed
      • Envision Ocular, LLC
    • Teaneck, New Jersey, United States, 07666
      • Completed
      • Retina Associates of NJ
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • Completed
      • University of New Mexico
  • New York
    • Great Neck, New York, United States, 11021
      • Completed
      • Long Is. Vitreoretinal Consult
    • Rochester, New York, United States, 14620
      • Completed
      • Retina Assoc of Western NY
    • Rockville Centre, New York, United States, 11570
      • Completed
      • Ophthalmic Consultants of Long Island
    • Syracuse, New York, United States, 13224
      • Completed
      • Retina Vit Surgeons/Central NY
  • North Carolina
    • Charlotte, North Carolina, United States, 28210
      • Completed
      • Char Eye Ear &Throat Assoc
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Active, not recruiting
      • Cincinnati Eye Institute
    • Cleveland, Ohio, United States, 44195
      • Completed
      • The Cleveland Clinic Foundation
    • Columbus, Ohio, United States, 43212
      • Active, not recruiting
      • OSU Eye Physicians & Surgeons
  • Oklahoma
    • Edmond, Oklahoma, United States, 73013
      • Completed
      • Retina Vitreous Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Completed
      • Oregon HSU
    • Portland, Oregon, United States, 97221
      • Completed
      • Retina Northwest
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Completed
      • Mid Atlantic Retina - Wills Eye Hospital
  • South Carolina
    • Florence, South Carolina, United States, 29501
      • Completed
      • Palmetto Retina Center
    • West Columbia, South Carolina, United States, 29169
      • Completed
      • Palmetto Retina Center, LLC
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Completed
      • Charles Retina Institute
    • Nashville, Tennessee, United States, 37203
      • Active, not recruiting
      • Tennessee Retina PC
  • Texas
    • Arlington, Texas, United States, 76012
      • Completed
      • Texas Retina Associates
    • Austin, Texas, United States, 78750
      • Active, not recruiting
      • Austin Clinical Research LLC
    • Austin, Texas, United States, 78705
      • Completed
      • Austin Retina Associates
    • Bellaire, Texas, United States, 77401
      • Completed
      • Retina Consultants of Texas
    • Fort Worth, Texas, United States, 76104
      • Completed
      • Texas Retina Associates
    • San Antonio, Texas, United States, 78240
      • Completed
      • Med Center Ophthalmology Assoc
    • The Woodlands, Texas, United States, 77384
      • Completed
      • Retina Consultants of Texas
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Completed
      • Rocky Mountain Retina
    • Salt Lake City, Utah, United States, 84107
      • Completed
      • Retina Associates of Utah, PLLC
  • Virginia
    • Virginia Beach, Virginia, United States, 23454
      • Completed
      • Wagner Kapoor Institute
  • Washington
    • Silverdale, Washington, United States, 98383
      • Completed
      • Pacific Northwest Retina
    • Spokane, Washington, United States, 99204
      • Completed
      • Spokane Eye Clinical Research

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Previous enrollment in and completion of Study GX28228 (Ladder) or Study GR40548 (Archway), without early treatment or study discontinuation in either study OR Previous enrollment in Study WR42221 (Velodrome) and either not eligible to be randomized in Study WR42221 at Week 24 or completed the study (from the Q24W or Q36W arm)
• Ability and willingness to undertake all scheduled visits and assessments
• For women of childbearing potential: agreement to remain abstinent or use contraceptive measures

Exclusion Criteria:

• Pregnant or breastfeeding, or intending to become pregnant during the treatment period and for at least 28 days after the last intravitreal injection of ranibizumab or 1 year after the last Implant refill-exchange of ranibizumab
• History of other ocular diseases that give reasonable suspicion of a disease or condition that contraindicates the use of ranibizumab, that might affect interpretation of the results of the study or that renders the participant at high risk for treatment complications
• History of other diseases, 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 that renders the participant at high risk of treatment complications
• Requirement for continuous use of any medications or treatments indicated in the "Prohibited Therapy"

Sub-study 1

Inclusion Criteria

- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures

Participants must meet the following ocular criteria for the study eye for substudy entry:

• Diagnosis of exudative nAMD within 2 years prior to the enrollment visit
• Previous treatment with at least two anti-VEGF ITV injections (e.g., ranibizumab, bevacizumab, or aflibercept) for nAMD per standard of care within 6 months prior to the enrollment visit
• Demonstrated response to prior anti-VEGF ITV treatment since diagnosis, as evidenced at enrollment by the following:

Overall decrease in nAMD disease activity detected on SD-OCT AND Stable or improved best-corrected visual acuity (BCVA)

• All subtypes of nAMD lesions are permissible (i.e., type I, type II, type III, or mixed forms per optical coherence tomography (OCT) classification) nAMD lesions at the time of diagnosis must involve the macula (6 mm diameter centered at the fovea).
• Sufficiently clear ocular media and adequate pupillary dilation to allow for analysis and grading by the central reading center of FP and SD-OCT images.

Exclusion Criteria Prior Ocular Treatments Study Eye

• History of vitrectomy surgery, submacular surgery, or other surgical intervention for AMD
• Prior treatment with Visudyne, external-beam radiation therapy, or transpupillary thermotherapy
• Previous treatment with corticosteroid ITV injection
• Previous intraocular device implantation
• Previous laser (any type) used for AMD treatment

Either Eye

• Treatment with anti-VEGF agents other than ranibizumab within 1 month prior to the enrollment visit
• Prior participation in a clinical trial involving anti-VEGF drugs within 6 months prior to the enrollment visit, other than ranibizumab

CNV Lesion Charateristics Study Eye

• Subretinal hemorrhage that involves the center of the fovea, if the hemorrhage is greater than 0.5 disc area (1.27 mm2 ) in size at screening
• Subfoveal fibrosis or subfoveal atrophy

Either Eye

- CNV due to other causes, such as ocular histoplasmosis, trauma, or pathologic myopia

Concurrent Ocular Conditions Study Eye

• Retinal pigment epithelial tear
• Any concurrent intraocular condition (e.g., cataract, glaucoma, diabetic retinopathy, or epiretinal membrane) 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
• Active intraocular inflammation (grade trace or above)
• History of vitreous hemorrhage
• History of rhegmatogenous retinal detachment
• History of rhegmatogenous retinal tears or peripheral retinal breaks within 3 months prior to the enrollment visit
• Aphakia or absence of the posterior capsule
• Previous violation of the posterior capsule is also an exclusion criterion unless it occurred as a result of yttrium-aluminum garnet (YAG) laser posterior capsulotomy in association with prior, posterior chamber intraocular lens implantation.
• Spherical equivalent of the refractive error demonstrating more than 8 diopters of myopia
• Preoperative refractive error that exceeds 8 diopters of myopia, for participants who have undergone prior refractive or cataract surgery in the study eye
• Intraocular surgery (including cataract surgery) within 3 months preceding the enrollment visit
• Uncontrolled ocular hypertension or glaucoma and any such condition the investigator determines may require a glaucoma-filtering surgery during a patient's participation in the study
• History of glaucoma-filtering surgery, tube shunts, or microinvasive glaucoma surgery
• History of corneal transplant
• History of prior vitrectomy surgery and absence of posterior capsule

Either Eye

• History of idiopathic or autoimmune-associated uveitis
• Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis

Concurrent Systemic Conditions

• Inability to comply with study schedule or procedures as described in the study protocol
• Uncontrolled blood pressure
• History of stroke within the last 3 months prior to informed consent
• Uncontrolled atrial fibrillation within 3 months of 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 patient at high risk of treatment complications in the opinion of the investigator
• Current systemic treatment for a confirmed active systemic infection
• Use of any systemic anti-VEGF agents
• Chronic use of oral corticosteroids
• Active cancer within 12 months of enrollment
• Previous participation in any non-ocular (systemic) disease studies of investigational drugs within 1 month preceding the informed consent (excluding vitamins and minerals)
• Use of antimitotic or antimetabolite therapy within 30 days or 5 elimination half-lives of the enrollment visit
• History of albinism
• Pregnant or breastfeeding, or intending to become pregnant during the treatment period and for at least 28 days after the last ITV injection of ranibizumab or 1 year after the last implant refill-exchange of ranibizumab

Sub-study 2

Inclusion Criteria:

• Having experienced septum dislodgement in the original implant while in the main study or after exiting the main study Ocular Inclusion Criteria for Study Eye
• Sufficiently clear ocular media and adequate pupillary dilation to allow for analysis and grading by central reading center

Exclusion Criteria (Cohort 1 only):

Concurrent Ocular Conditions-Study Eye

• Any ocular condition that may render the patient at high risk for surgical or treatment complications
• Intraocular surgery (including cataract surgery) within 1 month preceding the enrollment visit
• Any use of medicated intraocular implants (other than the PDS implant), at any time prior to enrollment
• History of rhegmatogenous retinal tears or peripheral retinal breaks within 3 months prior to the enrollment visit
• Any concurrent ocular condition that would require surgical intervention during the study to prevent or treat visual loss
• Concurrent conjunctival, Tenon's capsule, and/or scleral condition in the supero-temporal quadrant of the eye (e.g., scarring, thinning, mass) that may affect the refill-exchange procedure of the PDS implant
• Ongoing ocular complications that might affect participant safety

Concurrent Ocular Conditions-Either Eye

• Suspected or active ocular or periocular infection
• Any history of uveitis
• Active blepharitis

Concurrent Systemic Conditions

• Recent history (in the last 3 months prior to enrollment) of other disease, other non-diabetic metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a condition that contraindicates the use of ranibizumab or surgical placement of the PDS implant; that might affect interpretation of the results of the study; or that renders the participant at high risk for treatment complications
• Active cancer within the last 12 months, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or prostate cancer
• Current systemic treatment for a confirmed active systemic infection - Participation in an investigational trial that involves treatment with any drug or device (with the exception of vitamins and minerals or enrollment in the main study GR40549) within 6 months prior to enrollment.
• Use of antimitotic or antimetabolite therapy within 30 days or 5 elimination half-lives.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

11

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PDS Implant Cohort 1 (US only); Participants with PDS implant from Study GX28228 treated with refill-exchanges of 100 mg/mL ranibizumab Q24W. Participants will switch to an every 12 weeks (Q12W) visit schedule from Week 168 to Week 240. Eligible participants from Study GX28228 will be enrolled upon completion of their final visit.	Drug: PDS Implant with Ranibizumab 100 mg/mL; Will be administered as per the schedule described in individual arm
Experimental: PDS Implant Cohort 2 (US only); Participants with PDS implant from Study GR40548 treated with refill-exchanges of 100 mg/mL ranibizumab Q24W. Participants will switch to an every 12 weeks (Q12W) visit schedule from Week 144 to Week 240. Eligible participants from Study GR40548 will be enrolled upon completion of their final visit.	Drug: PDS Implant with Ranibizumab 100 mg/mL; Will be administered as per the schedule described in individual arm
Experimental: PDS Implant Cohort 3 (US only); Participants in the intravitreal ranibizumab arm of Study GX28228 who will receive the PDS implant upon study entry and refill-exchanges of 100 mg/mL ranibizumab Q24W. Participants will switch to an every 12 weeks (Q12W) visit schedule from Week 168 to Week 240. Eligible participants from Study GX28228 will be enrolled upon completion of their final visit.	Drug: PDS Implant with Ranibizumab 100 mg/mL; Will be administered as per the schedule described in individual arm
Experimental: PDS Implant Cohort 4 (US only); Participants in the intravitreal ranibizumab arm of Study GR40548 who will receive the PDS implant upon study entry and refill-exchanges of 100 mg/mL ranibizumab Q24W. Participants will switch to an every 12 weeks (Q12W) visit schedule from Week 144 to Week 240. Eligible participants from Study GR40548 will be enrolled upon completion of their final visit.	Drug: PDS Implant with Ranibizumab 100 mg/mL; Will be administered as per the schedule described in individual arm
Experimental: Sub-study 1: PDS Implant; Participants will receive PDS implant using TPC on Day 1 followed by refill-exchanges of ranibizumab 100 mg/mL via the PDS Q24W.	Drug: PDS Implant with Ranibizumab 100 mg/mL; Will be administered as per the schedule described in individual arm
Experimental: Sub-study 2: Cohort 2a; Participants who received an updated PDS implant, have < 24 weeks post-re-implantation follow-up and no refill exchange visit in the main study, will undergo two refill-exchange procedures with ranibizumab 100 mg/mL Q24W post main study re-implantation visit.	Drug: PDS Implant with Ranibizumab 100 mg/mL; Will be administered as per the schedule described in individual arm
Experimental: Sub-study 2: Cohort 2b; Participants who received an updated PDS implant, have < 48 weeks post-re-implantation follow-up and one refill exchange visit in the main study, will undergo one refill-exchange procedure with ranibizumab 100 mg/mL Q24W post main study re-implantation visit.	Drug: PDS Implant with Ranibizumab 100 mg/mL; Will be administered as per the schedule described in individual arm
Experimental: PDS Implant Cohort 5 (ex-US only); Participants from Study WR42221 who completed Week 24 but were not eligible to be randomized within WR42221 and who will be treated with refill-exchanges of ranibizumab 100 mg/mL Q24W. Participants will be in the study for a minimum of 144 weeks and may continue after Week 144 until the PDS has received Health Authority approval (or non-approval) in their respective country and/or until the decision to close the study has been made by the sponsor.	Drug: PDS Implant with Ranibizumab 100 mg/mL; Will be administered as per the schedule described in individual arm
Experimental: PDS Implant Cohort 6 (ex-US only); Participants from Study WR42221 randomized to the Q24W arm, who will continue to be treated with refill-exchanges of ranibizumab 100 mg/mL Q24W. Participants will be in the study for a minimum of 144 weeks and may continue after Week 144 until the PDS has received Health Authority approval (or non-approval) in their respective country and/or until the decision to close the study has been made by the sponsor.	Drug: PDS Implant with Ranibizumab 100 mg/mL; Will be administered as per the schedule described in individual arm
Experimental: PDS Implant Cohort 7 (ex-US only); Participants from Study WR42221 randomized to the Q36W arm, who will continue to be treated with refill-exchanges of ranibizumab 100 mg/mL Q36W. Participants will be in the study for a minimum of 144 weeks and may continue after Week 144 until the PDS has received Health Authority approval (or non-approval) in their respective country and/or until the decision to close the study has been made by the sponsor.	Drug: PDS Implant with Ranibizumab 100 mg/mL; Will be administered as per the schedule described in individual arm
Experimental: Sub-study 2: Cohort 1; Participants will undergo re-implantation with the updated PDS implant and receive 2 refill-exchanges of ranibizumab 100 mg/mL Q24W.	Drug: PDS Implant with Ranibizumab 100 mg/mL; Will be administered as per the schedule described in individual arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence and Severity of Ocular and Systemic (Non-Ocular) Adverse Events (AEs)	Baseline up to Week 240
Incidence, Severity, and Duration of Adverse Event of Special Interest (AESIs)	Baseline up to Week 240
Incidence, Severity, and Duration of PDS-Associated Ocular AESIs During the Postoperative Period (Up to 37 days of Initial Implantation) and Follow-Up Period (>37 days After Implantation Surgery) for Participants who Receive the PDS Implant in the Study	Baseline up to Week 240
Incidence and Severity of Adverse Device Effects	Baseline up to Week 240
Incidence, Causality, Severity, And Duration Of Anticipated Serious Adverse Device Effects	Baseline up to Week 240
Sub-study 1: Rate of Vitreous Hemorrhage Secondary to Choroidal Bleeding That Does not Resolve by the Week 4 Visit After Implant Insertion Surgery.	Baseline to Week 4
Sub-study 2: Number of Participants with Ocular and Systemic (Non-ocular) Adverse Events (AEs) and Severity of These AEs	Baseline to Week 72
Sub-study 2: Number of Participants with Adverse Events of Special Interests (AESIs) and Severity of AESIs	Baseline to Week 72
Sub-study 2: Duration of AESIs	Baseline to Week 72
Sub-study 2: Number of participants with Ocular AESIs and Severity of Ocular AESIs During the Post-operative Period	Up to Day 37 post re-implantation
Sub-study 2: Number of participants with Ocular AESIs and Severity of Ocular AESIs During the Follow-up Period	> 37 days post re-implantation (up to approximately Week 72)
Sub-study 2: Duration of Ocular AESIs During the Post-operative Period	Up to Day 37 post re-implantation
Sub-study 2: Duration of Ocular AESIs During the Follow-up Period	> 37 days post re-implantation (up to approximately Week 72)
Sub-study 2: Number of Participants with Adverse Device Effects (ADEs) and Severity of ADEs	Baseline to Week 72
Sub-study 2: Number of Participants with Anticipated Serious ADEs and Severity of Anticipated Serious ADEs	Baseline to Week 72
Sub-study 2: Duration of Anticipated Serious ADEs	Baseline to Week 72
Sub-study 2: Number of Device Deficiencies	Baseline to Week 72

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Best-Corrected Visual Acuity (BCVA) Score from Baseline Over Time, as Assessed using the ETDRS Visual Acuity Chart at a Starting Distance of 4 Meters	ETDRS = 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 up to Week 240
Percentage of Participants who Lose <15, <10, or <5 Letters in BCVA Score from Baseline Over Time		Baseline up to Week 240
Percentage of Participants with BCVA Score of 38 Letters (of 20/200 Approximate Snellen Equivalent) or Worse over Time		Baseline up to Week 240
Percentage of Participants with BCVA Score of 69 Letters (20/40 Approximate Snellen Equivalent) or Better over Time		Baseline up to Week 240
Percentage of Participants who Undergo Supplemental Treatment with Intravitreal Ranibizumab 0.5 mg During Each Refill-exchange Interval		Baseline up to Week 240
Sub-study 1: Incidence of Ocular Adverse Events (AEs) and Adverse Events of Special Interest (AESIs) in the Study eye		Baseline up to Week 104
Sub-study 1: Incidence of AEs Commonly Seen After Transscleral Cyclophotocoagulation (TS-CPC) for Treatment of Glaucoma in the Study eye		Baseline up to Week 104
Sub-study 1: Time From Surgery to Vitreous Hemorrhage Resolution in the Study eye		Baseline up to Week 104
Sub-study 1: Incidence of Vitreous Hemorrhage Grade 3 and Higher in the Study eye over time		Baseline up to Week 104
Sub-study 1: Distribution of Vitreous Hemorrhage Grade in the Study eye Over Time		Baseline up to Week 104
Sub-study 1: Rate of Vitrectomy in the Study eye		Baseline up to Week 104
Sub-study 1: Percentage of Participants who Lose <15, <10, or <5 Letters in BCVA Score From Baseline Over Time		Baseline up to Week 104
Sub-study 1: Change in BCVA Score From Baseline Over Time		Baseline up to Week 104
Sub-study 1: Change from Baseline in CPT Over Time		Baseline up to Week 104
Sub-study 1: Change From Baseline in Center Subfield Thickness (CST) Over Time		Baseline up to Week 104
Sub-study 2: Number of Participants with Ocular AESIs and Severity of AESIs Following Refill-exchange		Up to approximately Week 72
Sub-study 2: Duration of AESIs Following Refill-exchange		Up to approximately Week 72
Sub-study 2: Number of Participants With ADEs and Severity of ADEs Following Refill-exchange		Up to approximately Week 72
Sub-study 2: Number of Participants with Anticipated Serious ADEs and Severity of Anticipated Serious ADEs Following Refill-exchange		Up to approximately Week 72
Sub-study 2: Number of Device Deficiencies Following Refill-exchange		Up to approximately Week 72
Change from Baseline in Center Point Thickness (CPT) Over Time	CPT is defined as the retinal thickness in the center point of the fovea measured between the internal limiting membrane and the inner third of the retinal pigment epithelium layer. CPT is measured using optical coherence tomography (OCT).	Baseline up to Week 240

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Eichenbaum DA, Freeman WR, Chang MA, Brooks L, Chaudhry N, Dadgostar H, McCannel CA, Michels M, Mittra RA, Wolfe JD, Beindl VC, Jaycock P, Bobbala A, Gune S, Spicer G, Callaway N. Endophthalmitis in Eyes Treated with the Port Delivery System with Ranibizumab: Summary of Cases during Clinical Trial Development. Ophthalmol Retina. 2025 Feb;9(2):127-143. doi: 10.1016/j.oret.2024.08.005. Epub 2024 Aug 16.

Helpful Links

• Please use this form to submit your questions for a faster response: https://www.gene.com/contact-us/submit-medical-inquiry. Do not include or attach any medical records when emailing or completing the form. A nurse will respond within 24 business hours.

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2018
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: September 18, 2018
• First Submitted That Met QC Criteria: September 24, 2018
• First Posted (Actual): September 25, 2018

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: June 2, 2026
• Last Verified: June 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: GR40549; 2020-004427-16 (EudraCT Number); 2023-507131-38-00 (Ctis: EU CT Number)

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: No