Clinical trial NCT03683251: Extension Study for the Port Delivery System With Ranibizumab (Portal)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Neovascular Age-Related Macular Degeneration
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2018-09-25
Enrollment: 1000
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence and Severity of Ocular and Systemic (Non-Ocular) Adverse Events (AEs)
timeFrame: Baseline up to Week 240
measure: Incidence, Severity, and Duration of Adverse Event of Special Interest (AESIs)
timeFrame: Baseline up to Week 240
measure: 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
timeFrame: Baseline up to Week 240
measure: Incidence and Severity of Adverse Device Effects
timeFrame: Baseline up to Week 240
measure: Incidence, Causality, Severity, And Duration Of Anticipated Serious Adverse Device Effects
timeFrame: Baseline up to Week 240
measure: Sub-study 1: Rate of Vitreous Hemorrhage Secondary to Choroidal Bleeding That Does not Resolve by the Week 4 Visit After Implant Insertion Surgery.
timeFrame: Baseline to Week 4
measure: Sub-study 2: Number of Participants with Ocular and Systemic (Non-ocular) Adverse Events (AEs) and Severity of These AEs
timeFrame: Baseline to Week 72
measure: Sub-study 2: Number of Participants with Adverse Events of Special Interests (AESIs) and Severity of AESIs
timeFrame: Baseline to Week 72
measure: Sub-study 2: Duration of AESIs
timeFrame: Baseline to Week 72
measure: Sub-study 2: Number of participants with Ocular AESIs and Severity of Ocular AESIs During the Post-operative Period
timeFrame: Up to Day 37 post re-implantation
measure: Sub-study 2: Number of participants with Ocular AESIs and Severity of Ocular AESIs During the Follow-up Period
timeFrame: > 37 days post re-implantation (up to approximately Week 72)
measure: Sub-study 2: Duration of Ocular AESIs During the Post-operative Period
timeFrame: Up to Day 37 post re-implantation
measure: Sub-study 2: Duration of Ocular AESIs During the Follow-up Period
timeFrame: > 37 days post re-implantation (up to approximately Week 72)
measure: Sub-study 2: Number of Participants with Adverse Device Effects (ADEs) and Severity of ADEs
timeFrame: Baseline to Week 72
measure: Sub-study 2: Number of Participants with Anticipated Serious ADEs and Severity of Anticipated Serious ADEs
timeFrame: Baseline to Week 72
measure: Sub-study 2: Duration of Anticipated Serious ADEs
timeFrame: Baseline to Week 72
measure: Sub-study 2: Number of Device Deficiencies
timeFrame: Baseline to Week 72
Secondary outcomes:
measure: 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
timeFrame: Baseline up to Week 240
measure: Percentage of Participants who Lose <15, <10, or <5 Letters in BCVA Score from Baseline Over Time
timeFrame: Baseline up to Week 240
measure: Percentage of Participants with BCVA Score of 38 Letters (of 20/200 Approximate Snellen Equivalent) or Worse over Time
timeFrame: Baseline up to Week 240
measure: Percentage of Participants with BCVA Score of 69 Letters (20/40 Approximate Snellen Equivalent) or Better over Time
timeFrame: Baseline up to Week 240
measure: Change from Baseline in Center Point Thickness (CPT) Over Time
timeFrame: Baseline up to Week 240
measure: Percentage of Participants who Undergo Supplemental Treatment with Intravitreal Ranibizumab 0.5 mg During Each Refill-exchange Interval
timeFrame: Baseline up to Week 240
measure: Sub-study 1: Incidence of Ocular Adverse Events (AEs) and Adverse Events of Special Interest (AESIs) in the Study eye
timeFrame: Baseline up to Week 104
measure: Sub-study 1: Incidence of AEs Commonly Seen After Transscleral Cyclophotocoagulation (TS-CPC) for Treatment of Glaucoma in the Study eye
timeFrame: Baseline up to Week 104
measure: Sub-study 1: Time From Surgery to Vitreous Hemorrhage Resolution in the Study eye
timeFrame: Baseline up to Week 104
measure: Sub-study 1: Incidence of Vitreous Hemorrhage Grade 3 and Higher in the Study eye over time
timeFrame: Baseline up to Week 104
measure: Sub-study 1: Distribution of Vitreous Hemorrhage Grade in the Study eye Over Time
timeFrame: Baseline up to Week 104
measure: Sub-study 1: Rate of Vitrectomy in the Study eye
timeFrame: Baseline up to Week 104
measure: Sub-study 1: Percentage of Participants who Lose <15, <10, or <5 Letters in BCVA Score From Baseline Over Time
timeFrame: Baseline up to Week 104
measure: Sub-study 1: Change in BCVA Score From Baseline Over Time
timeFrame: Baseline up to Week 104
measure: Sub-study 1: Change from Baseline in CPT Over Time
timeFrame: Baseline up to Week 104
measure: Sub-study 1: Change From Baseline in Center Subfield Thickness (CST) Over Time
timeFrame: Baseline up to Week 104
measure: Sub-study 2: Number of Participants with Ocular AESIs and Severity of AESIs Following Refill-exchange
timeFrame: Up to approximately Week 72
measure: Sub-study 2: Duration of AESIs Following Refill-exchange
timeFrame: Up to approximately Week 72
measure: Sub-study 2: Number of Participants With ADEs and Severity of ADEs Following Refill-exchange
timeFrame: Up to approximately Week 72
measure: Sub-study 2: Number of Participants with Anticipated Serious ADEs and Severity of Anticipated Serious ADEs Following Refill-exchange
timeFrame: Up to approximately Week 72
measure: Sub-study 2: Number of Device Deficiencies Following Refill-exchange
timeFrame: Up to approximately Week 72
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Retinal Research Institute, LLC
state: Arizona
city: Phoenix
country: United States
facility: Arizona Retina and Vitreous Consultants
state: Arizona
city: Phoenix
country: United States
facility: Barnet Dulaney Perkins Eye Center
state: Arizona
city: Phoenix
country: United States
facility: Associated Retina Consultants
state: Arizona
city: Phoenix
country: United States
facility: Retinal Consultants of Arizona
state: Arizona
city: Bakersfield
country: United States
facility: California Retina Consultants
state: California
city: Beverly Hills
country: United States
facility: Retina-Vitreous Associates Medical Group
state: California
city: Encino
country: United States
facility: The Retina Partners
state: California
city: La Jolla
country: United States
facility: Jacobs Retina center at the Shiley eye Institute UCSD
state: California
city: Los Angeles
country: United States
facility: Jules Stein Eye Institute/ UCLA
state: California
city: Mountain View
country: United States
facility: N CA Retina Vitreous Assoc
state: California
city: Poway
country: United States
facility: Retina Consultants, San Diego
state: California
city: Sacramento
country: United States
facility: Retinal Consultants Med Group
state: California
city: San Francisco
country: United States
facility: West Coast Retina Medical Group
state: California
city: San Francisco
country: United States
facility: UCSF
state: California
city: Santa Ana
country: United States
facility: Orange County Retina Med Group
state: California
city: Santa Barbara
country: United States
facility: California Retina Consultants
state: California
city: Durango
country: United States
facility: Southwest Retina Consultants
state: Colorado
city: Fort Collins
country: United States
facility: Eye Center of Northern CO
state: Colorado
city: Lakewood
country: United States
facility: Colorado Retina Associates, PC
state: Colorado
city: Waterford
country: United States
facility: Retina Group of New England
state: Connecticut
city: Boynton Beach
country: United States
facility: Florida Eye Microsurgical Inst
state: Florida
city: Fort Myers
country: United States
facility: National Ophthalmic Research Institute
state: Florida
city: Melbourne
country: United States
facility: Florida Eye Associates
state: Florida
city: Palm Beach Gardens
country: United States
facility: Retina Care Specialists
state: Florida
city: Pensacola
country: United States
facility: Retina Specialty Institute
state: Florida
city: Plantation
country: United States
facility: Fort Lauderdale Eye Institute
state: Florida
city: Saint Petersburg
country: United States
facility: Retina Vitreous Assoc of FL
state: Florida
city: Tallahassee
country: United States
facility: Southern Vitreoretinal Assoc
state: Florida
city: Tampa
country: United States
facility: Retina Associates of Florida, LLC
state: Florida
city: Augusta
country: United States
facility: Southeast Retina Center
state: Georgia
city: Marietta
country: United States
facility: Georgia Retina PC
state: Georgia
city: Joliet
country: United States
facility: Illinois Retina Associates
state: Illinois
city: Oak Forest
country: United States
facility: University Retina and Macula Associates, PC
state: Illinois
city: West Des Moines
country: United States
facility: Wolfe Eye Clinic
state: Iowa
city: Lenexa
country: United States
facility: Retina Associates
state: Kansas
city: Lexington
country: United States
facility: Retina Associates of Kentucky
state: Kentucky
city: Paducah
country: United States
facility: Paducah Retinal Center
state: Kentucky
city: Portland
country: United States
facility: Maine Eye Center
state: Maine
city: Baltimore
country: United States
facility: Retina Specialists
state: Maryland
city: Baltimore
country: United States
facility: The Retina Care Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Med
state: Maryland
city: Chevy Chase
country: United States
facility: Retina Group of Washington
state: Maryland
city: Boston
country: United States
facility: Ophthalmic Consultants of Boston
state: Massachusetts
city: Grand Rapids
country: United States
facility: Foundation for Vision Research
state: Michigan
city: Royal Oak
country: United States
facility: Associated Retinal Consultants
state: Michigan
city: Minneapolis
country: United States
facility: VitreoRetinal Surgery, PLLC.
state: Minnesota
city: Chesterfield
country: United States
facility: Midwest Vision Research Foundation
state: Missouri
city: Chesterfield
country: United States
facility: The Retina Institute - Chesterfield
state: Missouri
city: Reno
country: United States
facility: Sierra Eye Associates
state: Nevada
city: Bloomfield
country: United States
facility: Envision Ocular, LLC
state: New Jersey
city: Teaneck
country: United States
facility: Retina Associates of NJ
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Great Neck
country: United States
facility: Long Is. Vitreoretinal Consult
state: New York
city: Rochester
country: United States
facility: Retina Assoc of Western NY
state: New York
city: Rockville Centre
country: United States
facility: Ophthalmic Consultants of Long Island
state: New York
city: Syracuse
country: United States
facility: Retina Vit Surgeons/Central NY
state: New York
city: Charlotte
country: United States
facility: Char Eye Ear &Throat Assoc
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Eye Institute
state: Ohio
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: OSU Eye Physicians & Surgeons
state: Ohio
city: Edmond
country: United States
facility: Retina Vitreous Center
state: Oklahoma
city: Portland
country: United States
facility: Retina Northwest
state: Oregon
city: Portland
country: United States
facility: Oregon HSU
state: Oregon
city: Philadelphia
country: United States
facility: Mid Atlantic Retina - Wills Eye Hospital
state: Pennsylvania
city: Florence
country: United States
facility: Palmetto Retina Center
state: South Carolina
city: West Columbia
country: United States
facility: Palmetto Retina Center, LLC
state: South Carolina
city: Germantown
country: United States
facility: Charles Retina Institute
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Retina PC
state: Tennessee
city: Arlington
country: United States
facility: Texas Retina Associates
state: Texas
city: Austin
country: United States
facility: Austin Retina Associates
state: Texas
city: Austin
country: United States
facility: Austin Clinical Research LLC
state: Texas
city: Fort Worth
country: United States
facility: Texas Retina Associates
state: Texas
city: Houston
country: United States
facility: Retina Consultants of Texas
state: Texas
city: San Antonio
country: United States
facility: Med Center Ophthalmology Assoc
state: Texas
city: The Woodlands
country: United States
facility: Retina Consultants of Texas
state: Texas
city: Salt Lake City
country: United States
facility: Retina Associates of Utah, PLLC
state: Utah
city: Salt Lake City
country: United States
facility: Rocky Mountain Retina
state: Utah
city: Virginia Beach
country: United States
facility: Wagner Kapoor Institute
state: Virginia
city: Silverdale
country: United States
facility: Pacific Northwest Retina
state: Washington
city: Spokane
country: United States
facility: Spokane Eye Clinical Research
state: Washington
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: Graz
country: Austria
facility: LKH-Univ.Klinikum Graz
city: Wien
country: Austria
facility: Medizinische Universität Wien
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg
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: Lyon cedex
country: France
facility: Hopital de la croix rousse
city: Marseille
country: France
facility: Centre Paradis Monticelli
city: Paris
country: France
facility: Hopital Lariboisiere
city: Bonn
country: Germany
facility: Universitatsklinikum Bonn
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg, Klinik für Augenheilkunde
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: München
country: Germany
facility: LMU Klinikum der Universität, Augenklinik
city: Münster
country: Germany
facility: Universitätsklinikum Münster
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: Roma
country: Italy
facility: Policlinico Universitario Agostino Gemelli
state: Lazio
city: Torrette - Ancona
country: Italy
facility: Azienda Ospedaliero Universitaria Ospedali Riuniti
state: Marche
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: Burjassot
country: Spain
facility: Oftalvist Valencia
state: Valencia
city: Barcelona
country: Spain
facility: Centro de Oftalmologia Barraquer
city: Barcelona
country: Spain
facility: Hospital dos de maig
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: 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 University Medical Faculty
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: Kings College Hospital NHS Foundation Trust
city: Newcastle upon Tyne
country: United Kingdom
facility: Royal Victoria Infirmary
city: Sunderland
country: United Kingdom
facility: Sunderland Eye Infirmary
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: