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

Neovascular Age-Related Macular Degeneration Clinical Trial

— 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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03683251
• Other study ID #: GR40549
• Secondary ID: 2020-004427-16
• Status: Recruiting
• Phase: Phase 3
• Start date: September 20, 2018
• Est. completion date: December 31, 2026

Study information

• Verified date: June 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID Number: GR40549 https://forpatients.roche.com
• Phone: 888-662-6728 (U.S. and Canada)
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

Inclusion Criteria:

• 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

Related Conditions & MeSH terms

• Macular Degeneration
• Neovascular Age-Related Macular Degeneration
• Wet Macular Degeneration

Intervention

Drug:
• PDS Implant with Ranibizumab 100 mg/mL
Will be administered as per the schedule described in individual arm

Locations

Country	Name	City	State
Argentina	Centro Oftalmológico Dr. Charles S.A.	Capital Federal
Argentina	Oftalmos	Capital Federal
Argentina	Grupo Laser Vision	Rosario
Australia	Eyeclinic Albury Wodonga	Albury	New South Wales
Australia	Eye and Retina Consultants	Hurstville	New South Wales
Austria	LKH-Univ.Klinikum Graz; Universitäts-Augenklinik	Graz
Austria	Medizinische Universität Wien; Universitätsklinik für Augenheilkunde und Optometrie	Wien
Belgium	UZ Leuven Gasthuisberg	Leuven
Brazil	Instituto da Visão	Belo Horizonte	MG
Brazil	Botelho Hospital da Visao	Blumenau	SC
Brazil	Centro Brasileiro de Cirurgia	Goiania	GO
Brazil	Hospital da Gamboa - Instituto de Oftalmologia do Rio de Janeiro	Rio de Janeiro	RJ
Brazil	Clinica de Olhos Dr Abujamra	Sao Paulo	SP
Brazil	Instituto da Visão IPEPO	Sao Paulo	SP
Brazil	Retina Clinic	Sao Paulo	SP
Brazil	Universidade Federal de Sao Paulo - UNIFESP*X; Oftalmologia	Sao Paulo	SP
France	Hopital Pellegrin; Ophtalmologie	Bordeaux
France	CHNO des Quinze Vingts; Ophtalmologie	Paris
Germany	Universitätsklinikum Ulm, Augenklinik und Poliklinik	Ulm
Israel	Rambam Medical Center; Opthalmology	Haifa
Israel	Hadassah MC; Ophtalmology	Jerusalem
Israel	Meir Medical Center; Ophtalmology	Kfar Saba
Israel	Rabin MC; Ophtalmology	Petach Tikva
Israel	Tel Aviv Sourasky MC; Ophtalmology	Tel Aviv
Italy	Policlinico Universitario Agostino Gemelli	Roma	Lazio
Spain	Hospital dos de maig; servicio de oftalmologia	Barcelona
Spain	Oftalvist Valencia	Burjassot	Valencia
Spain	Hospital Universitario Puerta de Hierro; Servicio de oftalmologia	Majadahonda	Madrid
Switzerland	Universitätsspital Basel Augenklinik Klinik	Basel
Switzerland	Inselspital Bern Ophthalmologische Klinik	Bern
Switzerland	Vista Klinik Ophthalmologische Klinik	Binningen
Switzerland	Fondation Asile Des Aveugles ? Jules Gonin Eye Hospital	Lausanne
Switzerland	Stadtspital Triemli Ophthalmologische Klinik	Zürich
Taiwan	Changhua Christian Hospital; Department of Ophthalmology	Changhua
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital; Ophthalmology	Kaohsiung
Taiwan	Taipei Veterans General Hospital; Ophthalmology	Taipei
Taiwan	Chang Gung Medical Foundation - Linkou; Ophthalmology	Taoyuan
Taiwan	National Taiwan University Hospital; Ophthalmology	Zhongzheng Dist.
United Kingdom	Royal Liverpool University Hospital; St Paul's Clinical Eye Research Centre	Liverpool
United Kingdom	Kings College Hospital NHS Foundation Trust	London
United Kingdom	Moorfields Eye Hospital NHS Foundation Trust	London
United Kingdom	Royal Victoria Infirmary	Newcastle upon Tyne
United Kingdom	Sunderland Eye Infirmary	Sunderland
United States	University of New Mexico; School of Med	Albuquerque	New Mexico
United States	Texas Retina Associates	Arlington	Texas
United States	Southeast Retina Center	Augusta	Georgia
United States	Austin Clinical Research LLC	Austin	Texas
United States	Austin Retina Associates	Austin	Texas
United States	California Retina Consultants	Bakersfield	California
United States	Johns Hopkins Med; Wilmer Eye Inst	Baltimore	Maryland
United States	The Retina Care Center	Baltimore	Maryland
United States	Retina-Vitreous Associates Medical Group	Beverly Hills	California
United States	Envision Ocular, LLC	Bloomfield	New Jersey
United States	Ophthalmic Consultants of Boston	Boston	Massachusetts
United States	Florida Eye Microsurgical Inst	Boynton Beach	Florida
United States	Char Eye Ear &Throat Assoc	Charlotte	North Carolina
United States	Midwest Vision Research Foundation	Chesterfield	Missouri
United States	The Retina Institute - Chesterfield	Chesterfield	Missouri
United States	Retina Group of Washington	Chevy Chase	Maryland
United States	Cincinnati Eye Institute	Cincinnati	Ohio
United States	The Cleveland Clinic Foundation	Cleveland	Ohio
United States	OSU Eye Physicians & Surgeons	Columbus	Ohio
United States	Southwest Retina Consultants	Durango	Colorado
United States	VitreoRetinal Surgery, PLLC.; DBA Retina Consultants of Minnesota	Edina	Minnesota
United States	Retina Vitreous Center	Edmond	Oklahoma
United States	The Retina Partners	Encino	California
United States	Eye Center of Northern CO	Fort Collins	Colorado
United States	National Ophthalmic Research Institute	Fort Myers	Florida
United States	Texas Retina Associates	Fort Worth	Texas
United States	Charles Retina Institute	Germantown	Tennessee
United States	Associated Retinal Consultants	Grand Rapids	Michigan
United States	Foundation for Vision Research	Grand Rapids	Michigan
United States	Long Is. Vitreoretinal Consult	Hauppauge	New York
United States	Illinois Retina Associates	Joliet	Illinois
United States	Jacobs Retina center at the Shiley eye Institute UCSD	La Jolla	California
United States	Colorado Retina Associates, PC	Lakewood	Colorado
United States	Retina Associates	Lenexa	Kansas
United States	Retina Associates of Kentucky	Lexington	Kentucky
United States	Retina Vit Surgeons/Central NY	Liverpool	New York
United States	Jules Stein Eye Institute/ UCLA	Los Angeles	California
United States	Georgia Retina PC	Marietta	Georgia
United States	Florida Eye Associates	Melbourne	Florida
United States	Barnet Dulaney Perkins Eye Center	Mesa	Arizona
United States	N CA Retina Vitreous Assoc	Mountain View	California
United States	Tennessee Retina PC	Nashville	Tennessee
United States	Wagner Kapoor Institute	Norfolk	Virginia
United States	University Retina and Macula Associates, PC	Oak Forest	Illinois
United States	Ophthalmic Consultants of Long Island	Oceanside	New York
United States	Paducah Retinal Center	Paducah	Kentucky
United States	Retina Care Specialists	Palm Beach Gardens	Florida
United States	Retina Specialty Institute	Pensacola	Florida
United States	Mid Atlantic Retina - Wills Eye Hospital	Philadelphia	Pennsylvania
United States	Arizona Retina and Vitreous Consultants	Phoenix	Arizona
United States	Associated Retina Consultants	Phoenix	Arizona
United States	Retinal Consultants of Arizona	Phoenix	Arizona
United States	Retinal Research Institute, LLC	Phoenix	Arizona
United States	Fort Lauderdale Eye Institute	Plantation	Florida
United States	Maine Eye Center	Portland	Maine
United States	Oregon HSU; Casey Eye Institute	Portland	Oregon
United States	Retina Northwest	Portland	Oregon
United States	Retina Consultants, San Diego	Poway	California
United States	Sierra Eye Associates	Reno	Nevada
United States	Retina Assoc of Western NY	Rochester	New York
United States	Retinal Consultants Med Group	Sacramento	California
United States	Retina Vitreous Assoc of FL	Saint Petersburg	Florida
United States	Retina Associates of Utah, PLLC	Salt Lake City	Utah
United States	Rocky Mountain Retina	Salt Lake City	Utah
United States	Med Center Ophthalmology Assoc	San Antonio	Texas
United States	UCSF; Ophthalmology	San Francisco	California
United States	West Coast Retina Medical Group	San Francisco	California
United States	Orange County Retina Med Group	Santa Ana	California
United States	California Retina Consultants	Santa Barbara	California
United States	Retina Center Northwest	Silverdale	Washington
United States	Spokane Eye Clinical Research	Spokane	Washington
United States	Southern Vitreoretinal Assoc	Tallahassee	Florida
United States	Retina Associates of Florida, LLC	Tampa	Florida
United States	Retina Associates of NJ	Teaneck	New Jersey
United States	Retina Consultants of Texas	The Woodlands	Texas
United States	Retina Specialists	Towson	Maryland
United States	Retina Group of New England	Waterford	Connecticut
United States	Palmetto Retina Center	West Columbia	South Carolina
United States	Palmetto Retina Center, LLC	West Columbia	South Carolina
United States	Wolfe Eye Clinic	West Des Moines	Iowa

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  France,  Germany,  Israel,  Italy,  Spain,  Switzerland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and Severity of Ocular and Systemic (Non-Ocular) Adverse Events (AEs)		Baseline up to Week 240
Primary	Incidence, Severity, and Duration of Adverse Event of Special Interest (AESIs)		Baseline up to Week 240
Primary	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
Primary	Incidence and Severity of Adverse Device Effects		Baseline up to Week 240
Primary	Incidence, Causality, Severity, And Duration Of Anticipated Serious Adverse Device Effects		Baseline up to Week 240
Primary	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	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
Secondary	Percentage of Participants who Lose <15, <10, or <5 Letters in BCVA Score from Baseline Over Time		Baseline up to Week 240
Secondary	Percentage of Participants with BCVA Score of 38 Letters (of 20/200 Approximate Snellen Equivalent) or Worse over Time		Baseline up to Week 240
Secondary	Percentage of Participants with BCVA Score of 69 Letters (20/40 Approximate Snellen Equivalent) or Better over Time		Baseline up to Week 240
Secondary	Change from Baseline in Center Point Thickness Over Time		Baseline up to Week 240
Secondary	Percentage of Participants who Undergo Supplemental Treatment with Intravitreal Ranibizumab 0.5 mg During Each Refill-exchange Interval		Baseline up to Week 240
Secondary	Substudy: Incidence of ocular adverse events and adverse events of special interest in the study eye		Baseline up to Week 240
Secondary	Substudy: Incidence of adverse events commonly seen after TS-CPC for treatment of glaucoma in the study eye		Baseline up to Week 240
Secondary	Substudy: Time from surgery to vitreous hemorrhage resolution in the study eye		Baseline up to Week 240
Secondary	Substudy: Incidence of vitreous hemorrhage Grade 3 and higher in the study eye over time		Baseline up to Week 240
Secondary	Substudy: Distribution of vitreous hemorrhage grade in the study eye over time		Baseline up to Week 240
Secondary	Substudy: Rate of vitrectomy in the study eye		Baseline up to Week 240
Secondary	Substudy: Percentage of Participants who Lose <15, <10, or <5 Letters in BCVA Score from Baseline Over Time		Baseline up to Week 240
Secondary	Substudy: Change in BCVA score from baseline over time		Baseline up to Week 240
Secondary	Substudy: Change from baseline in CPT over time		Baseline up to Week 240
Secondary	Substudy: Change from baseline in CST over time		Baseline up to Week 240