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 patients 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

• 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 Locations

• Argentina
  • Capital Federal, Argentina, C1015ABO
    • Recruiting
    • Centro Oftalmológico Dr. Charles S.A.
  • Capital Federal, Argentina, C1120AAN
    • Recruiting
    • Oftalmos
  • Rosario, Argentina, S2000DLA
    • Active, not recruiting
    • Grupo Laser Vision
• Australia
  • New South Wales
    • Albury, New South Wales, Australia, 2640
      • Recruiting
      • Eyeclinic Albury Wodonga
    • Hurstville, New South Wales, Australia, 2220
      • Recruiting
      • Eye and Retina Consultants
• Austria
  • Graz, Austria, 8036
    • Active, not recruiting
    • LKH-Univ.Klinikum Graz; Universitäts-Augenklinik
  • Wien, Austria, 1090
    • Recruiting
    • Medizinische Universität Wien; Universitätsklinik für Augenheilkunde und Optometrie
• Belgium
  • Leuven, Belgium, 3000
    • Recruiting
    • UZ Leuven Gasthuisberg
• Brazil
  • GO
    • Goiania, GO, Brazil, 74210-010
      • Withdrawn
      • Centro Brasileiro de Cirurgia
  • MG
    • Belo Horizonte, MG, Brazil, 30330-000
      • Withdrawn
      • Instituto da Visão
  • RJ
    • Rio de Janeiro, RJ, Brazil, 20220-324
      • Withdrawn
      • Hospital da Gamboa - Instituto de Oftalmologia do Rio de Janeiro
  • SC
    • Blumenau, SC, Brazil, 89052-504
      • Recruiting
      • Botelho Hospital da Visao
  • SP
    • Sao Paulo, SP, Brazil, 01427-002
      • Recruiting
      • Retina Clinic
    • Sao Paulo, SP, Brazil, 04023-062
      • Recruiting
      • Universidade Federal de Sao Paulo - UNIFESP*X; Oftalmologia
    • Sao Paulo, SP, Brazil, 04038-032
      • Recruiting
      • Instituto da Visão IPEPO
    • Sao Paulo, SP, Brazil, 01525-001
      • Withdrawn
      • Clinica de Olhos Dr Abujamra
• France
  • Bordeaux, France, 33000
    • Withdrawn
    • Hopital Pellegrin; Ophtalmologie
  • Paris, France, 75012
    • Withdrawn
    • CHNO des Quinze Vingts; Ophtalmologie
• Germany
  • Ulm, Germany, 89075
    • Recruiting
    • Universitätsklinikum Ulm, Augenklinik und Poliklinik
• Israel
  • Haifa, Israel, 3109601
    • Recruiting
    • Rambam Medical Center; Opthalmology
  • Jerusalem, Israel, 9112001
    • Recruiting
    • Hadassah MC; Ophtalmology
  • Kfar Saba, Israel, 4428164
    • Recruiting
    • Meir Medical Center; Ophtalmology
  • Petach Tikva, Israel, 4941492
    • Recruiting
    • Rabin MC; Ophtalmology
  • Tel Aviv, Israel, 6423906
    • Recruiting
    • Tel Aviv Sourasky MC; Ophtalmology
• Italy
  • Lazio
    • Roma, Lazio, Italy, 00168
      • Recruiting
      • Policlinico Universitario Agostino Gemelli
• Spain
  • Barcelona, Spain, 08025
    • Recruiting
    • Hospital dos de maig; servicio de oftalmologia
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Recruiting
      • Hospital Universitario Puerta de Hierro; Servicio de oftalmologia
  • Valencia
    • Burjassot, Valencia, Spain, 46100
      • Active, not recruiting
      • Oftalvist Valencia
• Switzerland
  • Basel, Switzerland, CH-4031
    • Recruiting
    • Universitätsspital Basel Augenklinik Klinik
  • Bern, Switzerland, 3010
    • Recruiting
    • Inselspital Bern Ophthalmologische Klinik
  • Binningen, Switzerland, 4102
    • Active, not recruiting
    • Vista Klinik Ophthalmologische Klinik
  • Lausanne, Switzerland, 1002
    • Recruiting
    • Fondation Asile Des Aveugles ? Jules Gonin Eye Hospital
  • Zürich, Switzerland, 8063
    • Active, not recruiting
    • Stadtspital Triemli Ophthalmologische Klinik
• Taiwan
  • Changhua, Taiwan, 500
    • Recruiting
    • Changhua Christian Hospital; Department of Ophthalmology
  • Kaohsiung, Taiwan
    • Recruiting
    • Kaohsiung Medical University Chung-Ho Memorial Hospital; Ophthalmology
  • Taipei, Taiwan, 11217
    • Recruiting
    • Taipei Veterans General Hospital; Ophthalmology
  • Taoyuan, Taiwan, 333
    • Recruiting
    • Chang Gung Medical Foundation - Linkou; Ophthalmology
  • Zhongzheng Dist., Taiwan, 10002
    • Recruiting
    • National Taiwan University Hospital; Ophthalmology
• United Kingdom
  • Liverpool, United Kingdom, L7 8YE
    • Recruiting
    • Royal Liverpool University Hospital; St Paul's Clinical Eye Research Centre
  • London, United Kingdom, SE5 9RS
    • Recruiting
    • Kings College Hospital NHS Foundation Trust
  • London, United Kingdom, EC1V 2PD
    • Active, not recruiting
    • Moorfields Eye Hospital NHS Foundation Trust
  • Newcastle upon Tyne, United Kingdom, NE1 4LP
    • Recruiting
    • Royal Victoria Infirmary
  • Sunderland, United Kingdom, SR2 9HP
    • Recruiting
    • Sunderland Eye Infirmary
• United States
  • Arizona
    • Mesa, Arizona, United States, 85206
      • Active, not recruiting
      • Barnet Dulaney Perkins Eye Center
    • Phoenix, Arizona, United States, 85020
      • Active, not recruiting
      • Associated Retina Consultants
    • Phoenix, Arizona, United States, 85053
      • Active, not recruiting
      • Retinal Consultants of Arizona
    • Phoenix, Arizona, United States, 85014
      • Completed
      • Retinal Research Institute, LLC
    • Phoenix, Arizona, United States, 85016
      • Active, not recruiting
      • Arizona Retina and Vitreous Consultants
  • California
    • Bakersfield, California, United States, 93309
      • Active, not recruiting
      • California Retina Consultants
    • Beverly Hills, California, United States, 90211
      • Active, not recruiting
      • 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
      • Active, not recruiting
      • N CA Retina Vitreous Assoc
    • Poway, California, United States, 92064
      • Completed
      • Retina Consultants, San Diego
    • Sacramento, California, United States, 95825
      • Active, not recruiting
      • Retinal Consultants Med Group
    • San Francisco, California, United States, 94143
      • Active, not recruiting
      • UCSF; Ophthalmology
    • San Francisco, California, United States, 94109
      • Completed
      • West Coast Retina Medical Group
    • Santa Ana, California, United States, 92705
      • Active, not recruiting
      • Orange County Retina Med Group
    • Santa Barbara, California, United States, 93103
      • Terminated
      • California Retina Consultants
  • Colorado
    • Durango, Colorado, United States, 81303
      • Active, not recruiting
      • Southwest Retina Consultants
    • Fort Collins, Colorado, United States, 80528
      • Active, not recruiting
      • Eye Center of Northern CO
    • Lakewood, Colorado, United States, 80228
      • Active, not recruiting
      • Colorado Retina Associates, PC
  • Connecticut
    • Waterford, Connecticut, United States, 06385
      • Active, not recruiting
      • Retina Group of New England
  • Florida
    • Boynton Beach, Florida, United States, 33426
      • Terminated
      • Florida Eye Microsurgical Inst
    • Fort Myers, Florida, United States, 33912
      • Active, not recruiting
      • National Ophthalmic Research Institute
    • Melbourne, Florida, United States, 32901
      • Active, not recruiting
      • Florida Eye Associates
    • Palm Beach Gardens, Florida, United States, 33410
      • Active, not recruiting
      • Retina Care Specialists
    • Pensacola, Florida, United States, 32503
      • Active, not recruiting
      • Retina Specialty Institute
    • Plantation, Florida, United States, 33324
      • Active, not recruiting
      • Fort Lauderdale Eye Institute
    • Saint 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
      • Active, not recruiting
      • Retina Associates of Florida, LLC
  • Georgia
    • Augusta, Georgia, United States, 30909
      • Active, not recruiting
      • Southeast Retina Center
    • Marietta, Georgia, United States, 30060-1137
      • Active, not recruiting
      • Georgia Retina PC
  • Illinois
    • Joliet, Illinois, United States, 60435
      • Active, not recruiting
      • Illinois Retina Associates
    • Oak Forest, Illinois, United States, 60452
      • Active, not recruiting
      • University Retina and Macula Associates, PC
  • Iowa
    • West Des Moines, Iowa, United States, 50266
      • Active, not recruiting
      • Wolfe Eye Clinic
  • Kansas
    • Lenexa, Kansas, United States, 66215
      • Active, not recruiting
      • Retina Associates
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • Active, not recruiting
      • Retina Associates of Kentucky
    • Paducah, Kentucky, United States, 42001
      • Completed
      • Paducah Retinal Center
  • Maine
    • Portland, Maine, United States, 04101
      • Active, not recruiting
      • Maine Eye Center
  • Maryland
    • Baltimore, Maryland, United States, 21209
      • Active, not recruiting
      • The Retina Care Center
    • Baltimore, Maryland, United States, 21287
      • Active, not recruiting
      • Johns Hopkins Med; Wilmer Eye Inst
    • Chevy Chase, Maryland, United States, 20815
      • Active, not recruiting
      • Retina Group of Washington
    • Towson, Maryland, United States, 21204
      • Active, not recruiting
      • Retina Specialists
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Active, not recruiting
      • Ophthalmic Consultants of Boston
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Active, not recruiting
      • Associated Retinal Consultants
    • Grand Rapids, Michigan, United States, 49546
      • Active, not recruiting
      • Foundation for Vision Research
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Active, not recruiting
      • VitreoRetinal Surgery, PLLC.; DBA Retina Consultants of Minnesota
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • Active, not recruiting
      • Midwest Vision Research Foundation
    • Chesterfield, Missouri, United States, 63017
      • Active, not recruiting
      • The Retina Institute - Chesterfield
  • Nevada
    • Reno, Nevada, United States, 89502
      • Active, not recruiting
      • Sierra Eye Associates
  • New Jersey
    • Bloomfield, New Jersey, United States, 07003
      • Active, not recruiting
      • Envision Ocular, LLC
    • Teaneck, New Jersey, United States, 07666
      • Active, not recruiting
      • Retina Associates of NJ
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • Completed
      • University of New Mexico; School of Med
  • New York
    • Hauppauge, New York, United States, 11788
      • Active, not recruiting
      • Long Is. Vitreoretinal Consult
    • Liverpool, New York, United States, 13088
      • Active, not recruiting
      • Retina Vit Surgeons/Central NY
    • Oceanside, New York, United States, 11572
      • Active, not recruiting
      • Ophthalmic Consultants of Long Island
    • Rochester, New York, United States, 14620
      • Completed
      • Retina Assoc of Western NY
  • North Carolina
    • Charlotte, North Carolina, United States, 28210
      • Terminated
      • Char Eye Ear &Throat Assoc
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Active, not recruiting
      • Cincinnati Eye Institute
    • Cleveland, Ohio, United States, 44195
      • Active, not recruiting
      • The Cleveland Clinic Foundation
    • Columbus, Ohio, United States, 43212
      • Active, not recruiting
      • OSU Eye Physicians & Surgeons
  • Oklahoma
    • Edmond, Oklahoma, United States, 73013
      • Recruiting
      • Retina Vitreous Center
  • Oregon
    • Portland, Oregon, United States, 97221
      • Active, not recruiting
      • Retina Northwest
    • Portland, Oregon, United States, 97239
      • Completed
      • Oregon HSU; Casey Eye Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Active, not recruiting
      • Mid Atlantic Retina - Wills Eye Hospital
  • South Carolina
    • West Columbia, South Carolina, United States, 29169
      • Active, not recruiting
      • Palmetto Retina Center, LLC
    • West Columbia, South Carolina, United States, 29169
      • Active, not recruiting
      • Palmetto Retina Center
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Active, not recruiting
      • Charles Retina Institute
    • Nashville, Tennessee, United States, 37203
      • Active, not recruiting
      • Tennessee Retina PC
  • Texas
    • Arlington, Texas, United States, 76012
      • Active, not recruiting
      • Texas Retina Associates
    • Austin, Texas, United States, 78750
      • Active, not recruiting
      • Austin Clinical Research LLC
    • Austin, Texas, United States, 78705-1169
      • Active, not recruiting
      • Austin Retina Associates
    • Fort Worth, Texas, United States, 76104
      • Active, not recruiting
      • Texas Retina Associates
    • San Antonio, Texas, United States, 78240
      • Active, not recruiting
      • Med Center Ophthalmology Assoc
    • The Woodlands, Texas, United States, 77384-4167
      • Active, not recruiting
      • Retina Consultants of Texas
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Active, not recruiting
      • Rocky Mountain Retina
    • Salt Lake City, Utah, United States, 84107
      • Active, not recruiting
      • Retina Associates of Utah, PLLC
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Active, not recruiting
      • Wagner Kapoor Institute
  • Washington
    • Silverdale, Washington, United States, 98383
      • Active, not recruiting
      • Retina Center Northwest
    • Spokane, Washington, United States, 99204
      • Active, not recruiting
      • 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"

Substudy

Inclusion Criteria

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

Patients 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 patients 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

7

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: 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	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	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	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
Substudy: 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

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
Change from Baseline in Center Point Thickness 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
Substudy: Incidence of ocular adverse events and adverse events of special interest in the study eye		Baseline up to Week 240
Substudy: Incidence of adverse events commonly seen after TS-CPC for treatment of glaucoma in the study eye		Baseline up to Week 240
Substudy: Time from surgery to vitreous hemorrhage resolution in the study eye		Baseline up to Week 240
Substudy: Incidence of vitreous hemorrhage Grade 3 and higher in the study eye over time		Baseline up to Week 240
Substudy: Distribution of vitreous hemorrhage grade in the study eye over time		Baseline up to Week 240
Substudy: Rate of vitrectomy in the study eye		Baseline up to Week 240
Substudy: Percentage of Participants who Lose <15, <10, or <5 Letters in BCVA Score from Baseline Over Time		Baseline up to Week 240
Substudy: Change in BCVA score from baseline over time		Baseline up to Week 240
Substudy: Change from baseline in CPT over time		Baseline up to Week 240
Substudy: Change from baseline in CST over time		Baseline up to Week 240

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2018
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

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 (Estimated): May 13, 2024
• Last Update Submitted That Met QC Criteria: May 10, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Wet Macular Degeneration; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Ranibizumab
• Other Study ID Numbers: GR40549; 2020-004427-16 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No