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NCT03683251PHASE3Recruiting

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

Hoffmann-La Roche

Start Date

9/20/2018

Completion Date

12/31/2029

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

Age Range: 50 years to No maximum

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.

Interventions

DRUG

PDS Implant with Ranibizumab 100 mg/mL

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Conditions

Neovascular Age-Related Macular Degeneration

Locations

Retinal Research Institute, LLC

Phoenix, Arizona 85014

United States

Arizona Retina and Vitreous Consultants

Phoenix, Arizona 85016

United States

Barnet Dulaney Perkins Eye Center

Phoenix, Arizona 85016

United States

Associated Retina Consultants

Phoenix, Arizona 85020

United States

Retinal Consultants of Arizona

Phoenix, Arizona 85053

United States

California Retina Consultants

Bakersfield, California 93309

United States

Retina-Vitreous Associates Medical Group

Beverly Hills, California 90211

United States

The Retina Partners

Encino, California 91436

United States

Jacobs Retina center at the Shiley eye Institute UCSD

La Jolla, California 92037

United States

Jules Stein Eye Institute/ UCLA

Los Angeles, California 90095-7000

United States

N CA Retina Vitreous Assoc

Mountain View, California 94040

United States

Retina Consultants, San Diego

Poway, California 92064

United States

Retinal Consultants Med Group

Sacramento, California 95841

United States

West Coast Retina Medical Group

San Francisco, California 94109

United States

UCSF

San Francisco, California 94158

United States

Orange County Retina Med Group

Santa Ana, California 92705

United States

California Retina Consultants

Santa Barbara, California 93103

United States

Southwest Retina Consultants

Durango, Colorado 81303

United States

Eye Center of Northern CO

Fort Collins, Colorado 80528

United States

Colorado Retina Associates, PC

Lakewood, Colorado 80228

United States

Retina Group of New England

Waterford, Connecticut 06385

United States

Florida Eye Microsurgical Inst

Boynton Beach, Florida 33426

United States

National Ophthalmic Research Institute

Fort Myers, Florida 33912

United States

Florida Eye Associates

Melbourne, Florida 32901

United States

Retina Care Specialists

Palm Beach Gardens, Florida 33410

United States

Retina Specialty Institute

Pensacola, Florida 32503

United States

Fort Lauderdale Eye Institute

Plantation, Florida 33324

United States

Retina Vitreous Assoc of FL

St. Petersburg, Florida 33711

United States

Southern Vitreoretinal Assoc

Tallahassee, Florida 32308

United States

Retina Associates of Florida, LLC

Tampa, Florida 33609

United States

Southeast Retina Center

Augusta, Georgia 30909

United States

Georgia Retina PC

Marietta, Georgia 30060

United States

Illinois Retina Associates

Joliet, Illinois 60435

United States

University Retina and Macula Associates, PC

Oak Forest, Illinois 60452

United States

Wolfe Eye Clinic

West Des Moines, Iowa 50266

United States

Retina Associates

Lenexa, Kansas 66215

United States

Retina Associates of Kentucky

Lexington, Kentucky 40509

United States

Paducah Retinal Center

Paducah, Kentucky 42001

United States

Maine Eye Center

Portland, Maine 04101

United States

The Retina Care Center

Baltimore, Maryland 21209

United States

Johns Hopkins Med

Baltimore, Maryland 21287

United States

Retina Group of Washington

Chevy Chase, Maryland 20815

United States

Retina Specialists

Towson, Maryland 21204

United States

Ophthalmic Consultants of Boston

Boston, Massachusetts 02114

United States

Foundation for Vision Research

Grand Rapids, Michigan 49546

United States

Associated Retinal Consultants

Royal Oak, Michigan 48073

United States

VitreoRetinal Surgery, PLLC.

Minneapolis, Minnesota 55435

United States

Midwest Vision Research Foundation

Chesterfield, Missouri 63017

United States

The Retina Institute - Chesterfield

St Louis, Missouri 63128

United States

Sierra Eye Associates

Reno, Nevada 89502

United States

Envision Ocular, LLC

Bloomfield, New Jersey 07003

United States

Retina Associates of NJ

Teaneck, New Jersey 07666

United States

University of New Mexico

Albuquerque, New Mexico 87131

United States

Long Is. Vitreoretinal Consult

Great Neck, New York 11021

United States

Retina Assoc of Western NY

Rochester, New York 14620

United States

Ophthalmic Consultants of Long Island

Rockville Centre, New York 11570

United States

Retina Vit Surgeons/Central NY

Syracuse, New York 13224

United States

Char Eye Ear &Throat Assoc

Charlotte, North Carolina 28210

United States

Cincinnati Eye Institute

Cincinnati, Ohio 45242

United States

The Cleveland Clinic Foundation

Cleveland, Ohio 44195

United States

OSU Eye Physicians & Surgeons

Columbus, Ohio 43212

United States

Retina Vitreous Center

Edmond, Oklahoma 73013

United States

Retina Northwest

Portland, Oregon 97221

United States

Oregon HSU

Portland, Oregon 97239

United States

Mid Atlantic Retina - Wills Eye Hospital

Philadelphia, Pennsylvania 19107

United States

Palmetto Retina Center

Florence, South Carolina 29501

United States

Palmetto Retina Center, LLC

West Columbia, South Carolina 29169

United States

Charles Retina Institute

Germantown, Tennessee 38138

United States

Tennessee Retina PC

Nashville, Tennessee 37203

United States

Texas Retina Associates

Arlington, Texas 76012

United States

Austin Retina Associates

Austin, Texas 78705

United States

Austin Clinical Research LLC

Austin, Texas 78750

United States

Retina Consultants of Texas

Bellaire, Texas 77401

United States

Texas Retina Associates

Fort Worth, Texas 76104

United States

Med Center Ophthalmology Assoc

San Antonio, Texas 78240

United States

Retina Consultants of Texas

The Woodlands, Texas 77384

United States

Retina Associates of Utah, PLLC

Salt Lake City, Utah 84107

United States

Rocky Mountain Retina

Salt Lake City, Utah 84107

United States

Wagner Kapoor Institute

Virginia Beach, Virginia 23454

United States

Pacific Northwest Retina

Silverdale, Washington 98383

United States

Spokane Eye Clinical Research

Spokane, Washington 99204

United States

Oftalmos

Capital Federal, C1120AAN

Argentina

Centro Oftalmologico Dr. Charles S.A.

Ciudad Autonoma Buenos Aires, C1121ABB

Argentina

Grupo Laser Vision

Rosario, S2000DLA

Argentina

Eyeclinic Albury Wodonga

Albury, New South Wales 2640

Australia

Eye and Retina Consultants

Hurstville, New South Wales 2220

Australia

LKH-Univ.Klinikum Graz

Graz, 8036

Austria

Medizinische Universitat Wien

Vienna, 1090

Austria

UZ Leuven Gasthuisberg

Leuven, 3000

Belgium

Botelho Hospital da Visao

Blumenau, Santa Catarina 89052-504

Brazil

Retina Clinic

São Paulo, São Paulo 01427-002

Brazil

Universidade Federal de Sao Paulo - UNIFESPX

São Paulo, São Paulo 04023-062

Brazil

Instituto da Visao IPEPO

São Paulo, São Paulo 04038-032

Brazil

Hosp de Olhos de Sorocaba

Sorocaba, São Paulo 18031-060

Brazil

Centre Retine Gallien

Bordeaux, 33000

France

Hopital de la croix rousse

Lyon, 69317

France

Centre Paradis Monticelli

Marseille, 13008

France

Hopital Lariboisiere

Paris, 75010

France

Fondation Rothschild

Paris, 75940

France

Universitatsklinikum Bonn

Bonn, 53127

Germany

Universitatsklinikum Koln

Cologne, 50937

Germany

Medizinische Universitat Lausitz ? Carl Thiem

Cottbus, 03048

Germany

Universitätsklinikum Freiburg, Klinik für Augenheilkunde

Freiburg im Breisgau, 79106

Germany

Universitatsklinikum Hamburg-Eppendorf

Hamburg, 20246

Germany

Klinikum der Stadt Ludwigshafen am Rhein gGmbH

Ludwigshafen, 67063

Germany

LMU Klinikum der Universitat, Augenklinik

München, 80336

Germany

Augenabteilung am St. Franziskus-Hospital

Münster, 48145

Germany

Universitatsklinikum Munster

Münster, 48149

Germany

Knappschaftsklinikum Saar GmbH

Sulzbach, 66280

Germany

Universitatsklinikum Tubingen

Tübingen, 72076

Germany

Universitatsklinikum Ulm, Augenklinik und Poliklinik

Ulm, 89075

Germany

Rambam Medical Center

Haifa, 3109601

Israel

Hadassah MC

Jerusalem, 9112001

Israel

Meir Medical Center

Kfar Saba, 4428164

Israel

Rabin MC

Petah Tikva, 4941492

Israel

Kaplan Medical Center

Rehovot, 7660101

Israel

Tel Aviv Sourasky MC

Tel Aviv, 6423906

Israel

Ospedale Clinicizzato SS Annunziata

Chieti, Abruzzo 66100

Italy

Policlinico di Bari

Bari, Apulia 70124

Italy

Azienda Ospedaliero Universitaria "Ospedali Riuniti" Trieste-Ospedale Maggiore

Trieste, Friuli Venezia Giulia 34129

Italy

Policlinico Universitario Agostino Gemelli

Rome, Lazio 00168

Italy

Fondazione G.B. Bietti Per Lo Studio E La Ricerca in Oftalmologia-Presidio Ospedaliero Britannico

Rome, Lazio 00198

Italy

Fondazione Irccs Ca' Granda Ospedale Maggiore Policlinico-Clinica Regina Elena

Milan, Lombardy 20100

Italy

Irccs Ospedale San Raffaele

Milan, Lombardy 20132

Italy

Asst Fatebenefratelli Sacco

Milan, Lombardy 20157

Italy

Azienda Ospedaliero Universitaria Ospedali Riuniti

Torrette - Ancona, The Marches 60126

Italy

Azienda Ospedaliero-Universitaria Careggi

Florence, Tuscany 50134

Italy

Azienda Ospedaliera di Perugia Ospedale S. Maria Della Misericordia

Perugia, Umbria 06129

Italy

Ospedale Classificato Equiparato Sacro Cuore ? Don Calabria

Negrar - Verona, Veneto 37024

Italy

A.O. Universitaria S. Maria Della Misericordia Di Udine

Udine, Veneto 33100

Italy

Hospital Universitario de Bellvitge

L'Hospitalet de Llobregat, Barcelona 08907

Spain

Hospital General de Catalunya

San Cugat Del Valles, Barcelona 08195

Spain

Hospital Universitario Puerta de Hierro

Majadahonda, Madrid 28222

Spain

Clinica Universitaria de Navarra

Pamplona, Navarre 31008

Spain

Instituto Oftalmologico Fernandez Vega

Oviedo, Principality of Asturias 33012

Spain

Oftalvist Valencia

Burjassot, Valencia 46100

Spain

Centro de Oftalmologia Barraquer

Barcelona, 08021

Spain

Institut de la Macula i la retina

Barcelona, 08022

Spain

Hospital dos de maig

Barcelona, 08025

Spain

Hospital Universitari Vall d'Hebron

Barcelona, 08035

Spain

Hospital de la Arruzafa. Servicio de Oftalmologia

Córdoba, 14012

Spain

Clinica Baviera

Madrid, 28046

Spain

Universitatsspital Basel Augenklinik Klinik

Basel, 4056

Switzerland

Inselspital Bern Ophthalmologische Klinik

Bern, 3010

Switzerland

Vista Klinik Ophthalmologische Klinik

Binningen, 4102

Switzerland

Fondation Asile Des Aveugles ? Jules Gonin Eye Hospital

Lausanne,

Switzerland

Stadtspital Triemli Ophthalmologische Klinik

Zurich, 8063

Switzerland

Changhua Christian Hospital

Changhua, 500

Taiwan

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City,

Taiwan

Taipei Veterans General Hospital

Taipei, 11217

Taiwan

Chang Gung Medical Foundation - Linkou

Taoyuan, 333

Taiwan

National Taiwan University Hospital

Zhongzheng Dist., 10002

Taiwan

Hacettepe University Medical Faculty

Ankara, 06100

Turkey (Türkiye)

Ankara Bilkent City Hospital

Ankara, 06490

Turkey (Türkiye)

Ankara Etlik City Hospital

Ankara, DUMMY_VALUE

Turkey (Türkiye)

Beyoglu Goz Training and Research Hospital

Istanbul, 34421

Turkey (Türkiye)

Kocaeli University Medical Faculty

Kocaeli, 41380

Turkey (Türkiye)

Bristol Eye Hospital

Bristol, BS1 2LX

United Kingdom

Royal Liverpool University Hospital

Liverpool, L7 8XP

United Kingdom

Moorfields Eye Hospital NHS Foundation Trust

London, EC1V 2PD

United Kingdom

Central Middlesex Hospital

London, NW10 7NS

United Kingdom

Kings College Hospital NHS Foundation Trust

London, SE5 9RS

United Kingdom

Royal Victoria Infirmary

Newcastle upon Tyne, NE1 4LP

United Kingdom

Sunderland Eye Infirmary

Sunderland, SR2 9HP

United Kingdom

Royal Wolverhampton hospital

Wolverhampton, WV10 0QP

United Kingdom