Clinical trial NCT04853251: A Study Assessing Corneal Endothelial Cells in Participants With Neovascular Age-related Macular Degeneration(nAMD) Treated With the Port Delivery System With Ranibizumab (PDS)
Official title: A Phase IV, Multicenter, Open-Label Study to Assess Corneal Endothelial Cells in Patients With Neovascular Age-Related Macular Degeneration Treated With the Port Delivery System With Ranibizumab (PDS)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Neovascular Age-related Macular Degeneration
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2021-04-21
Enrollment: 188
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will assess corneal endothelial cells in participants with nAMD treated with PDS refilled every 24 weeks (Q24W).


Eligibility criteria: Inclusion Criteria

Ocular Inclusion Criteria:

* Initial diagnosis of nAMD within 18 months prior to screening
* Difference of \<10% in ECD at screening between the 2 eyes as measured by specular microscopy and determined by the independent reading center
* Availability of historical visual acuity (VA) data and spectral-domain optical coherence tomography (SD-OCT) imaging prior to the first anti-vascular endothelial growth factor (VEGF) intravitreal therapy (IVT) treatment for nAMD
* Availability of comprehensive historical anti-VEGF injection data including anti-VEGF agent administered and date of administration from the first anti-VEGF treatment for nAMD
* Demonstrated response to at least two anti-VEGF IVT injections since diagnosis, as evidenced by the following:

  * Overall decrease in nAMD disease activity detected on historical or screening OCT as assessed by the investigator and confirmed by the central reading center AND
  * Stable or improved BCVA
* Best-corrected visual acuity (BCVA) of 34 letters (approximate 20/200 Snellen equivalent) or better, using Early Treatment of Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters at screening and enrollment
* All subtypes of nAMD lesions are permissible
* nAMD lesions at the time of diagnosis must involve the macula (6 millimetres (mm) diameter centered at the fovea)
* Sufficiently clear ocular media and adequate pupillary dilation to allow for clinical examination and analysis and grading by the central reading center of SD-OCT images

Exclusion Criteria

Prior Ocular Treatment

Study Eye:

* Prior treatment with verteporfin for injection, external-beam radiation therapy, or transpupillary thermotherapy
* Previous treatment with corticosteroid IVT injection
* Previous laser (any type) used for age related macular degeneration (AMD) treatment
* History of vitreous hemorrhage
* History of rhegmatogenous retinal detachment
* History of corneal transplant
* History of conjunctival surgery in the superotemporal quadrant

Either Eye:

* Previous PDS implantation
* Previous intraocular surgery (including cataract surgery) within 6 months of study enrollment
* Prior pars plana vitrectomy surgery
* Previous intraocular device implantation excluding intraocular lenses
* History of glaucoma-filtering surgery, tube shunts, or microinvasive glaucoma surgery
* Intraocular laser therapy including selective laser trabeculoplasty, yttrium-aluminum garnet (YAG), prophylactic peripheral iridotomy within 1 year of screening, or YAG capsulotomy within 3 months of screening
* Contact lens wear in either eye within 2 months of screening
* Any prior ocular trauma (blunt or penetrating)
* History of corneal transplantation, including partial-thickness corneal grafts
* Prior treatment with brolucizumab
* Prior treatment with any anti-VEGF biosimilar agents within 2 months of screening
* Prior treatment with faricimab within 2 months of screening
* Prior treatment with aflibercept 8 mg within 2 months of screening
* Prior treatment with external-beam radiation therapy or brachytherapy

Macular Neovascularization Lesion (MNV) Characteristics

Study Eye:

* Subretinal hemorrhage that involves the center of the fovea, if the hemorrhage is greater than 0.5-disc area (1.27 square millimitres (mm\^2)) in size at screening
* Subfoveal fibrosis or subfoveal atrophy

Concurrent Ocular Conditions

Study Eye:

* Retinal pigment epithelial tear
* Retinal tears or peripheral retinal breaks on depressed fundus exam that are untreated, or treated within the 3 months prior to study enrollment
* Previous violation of the posterior capsule is also an exclusion criterion unless it occurred as a result of 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 or evidence of pathologic myopia on depressed fundus exam
* Preoperative refractive error that exceeds 8 diopters of myopia, for participants who have undergone prior refractive or cataract surgery
* Spherical equivalent of the refractive error demonstrating more than 5 diopters of hyperopia
* Preoperative refractive error that exceeds 5 diopters of hyperopia, for participants who have undergone prior refractive or cataract surgery
* Uncontrolled ocular hypertension or glaucoma
* Scleral pathology in the superotemporal quadrant (e.g., scleral thinning or calcification)
* Conjunctival pathologies in the superotemporal quadrant
* History or presence of severe posterior blepharitis, recurrent chalazia or hordeolum, severe dry eye syndrome, or severe allergic conjunctivitis
* Ectropion, entropion or other impairment of the upper or lower eyelid impacting lid functionality needed to protect the ocular surface from exposure
* Trichiasis
* Corneal neuropathy
* Lagophthalmos or incomplete blink • Active or history of facial nerve palsy/paresis

Fellow (Non-Study) Eye:

• Concurrent PDS implantation

Either Eye:

* Aphakia or absence of the posterior capsule
* Any concurrent intraocular condition 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
* Corneal ECD ≤1500 cells/mm2 in either eye at screening as determined by the independent reading center
* Fuchs endothelial corneal dystrophy Grade ≥ 2
* Previous corneal endothelial cell damage, including from blunt or surgical trauma
* Any ocular condition that precludes obtaining an analyzable specular microscopy image
* Active or history of corneal edema
* Active or history of corneal dystrophies
* Active or history of iridocorneal endothelial syndrome
* Active or history of pseudoexfoliation syndrome
* Active or history of herpetic keratitis or kerato-uveitis
* Any active or history of uveitis
* Active or history of keratitis, scleritis, or endophthalmitis
* Active ocular or periocular infection
* Active or history of Sjogren's syndrome or keratoconjunctivitis sicca
* Active or history of floppy eyelid syndrome
* Active or history of chronic eye rubbing
* Active thyroid eye disease

Concurrent Systemic Conditions:

* Uncontrolled blood pressure
* Active or history of autoimmune diseases such as rheumatoid arthritis, lupus, granulomatosis with polyangiitis (Wegner's), etc.
* History of stroke within the last 3 months prior to screening
* Uncontrolled atrial fibrillation within 3 months of screening
* History of myocardial infarction within the last 3 months prior to screening
* 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 active systemic infection
* Use of any systemic anti-VEGF agents
* Chronic use of oral corticosteroids
* Active cancer within 12 months of enrollment except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, and prostate cancer with a Gleason score of ≤ 6 and a stable prostate-specific antigen for \> 12 months
* Previous participation in any non-ocular (systemic) disease studies of investigational drugs within 1 month prior to screening (excluding vitamins and minerals)
* Use of antimitotic or antimetabolite therapy within 30 days or 5 elimination half-lives of the screening visit
* Pregnant or breastfeeding, or intention to become pregnant during the study
* Women of childbearing potential, must have a negative urine pregnancy test result within 28 days prior to initiation of study treatment. If the urine pregnancy test is positive, it must be confirmed by a serum pregnancy test.

Primary outcomes:
measure: Percent Change in Corneal Endothelial Cell Density (ECD) From Baseline at Week 48 in the Study Eye as Compared With the Fellow Eye, as Assessed by Specular Microscopy
timeFrame: Baseline, Week 48
Secondary outcomes:
measure: Percent Change in Corneal ECD From Baseline at Week 24 in the Study Eye as Compared With the Fellow Eye
timeFrame: Baseline, Week 24
measure: Percent Change in the Coefficient of Variation (CV) of Corneal Endothelial Cell Area From Baseline at Weeks 24 and 48 in the Study Eye as Compared With the Fellow Eye
timeFrame: Baseline, Week 24, Week 48
measure: Percent Change in Hexagonal Cells (HEX) From Baseline at Weeks 24 and 48 in the Study Eye as Compared With the Fellow Eye
timeFrame: Baseline, Week 24, Week 48
measure: Percentage of Participants With Ocular Serious Adverse Events (SAEs) and Severity of SAEs
timeFrame: Day 1 up to approximately Week 52
measure: Percentage of Participants With Ocular Adverse Events of Special Interests (AESIs) and Severity of Ocular AESIs
timeFrame: Day 1 to Week 52
measure: Duration of Ocular AESIs
timeFrame: Day 1 to Week 52
measure: Percentage of Participants With Ocular AESIs During the Postoperative Period
timeFrame: Baseline up to 37 days of initial implantation
measure: Percentage of Participants With Ocular AESIs During the Intermediate Postoperative Period
timeFrame: 38 to 93 days after implantation
measure: Percentage of Participants With Ocular AESIs During the Follow-up Period
timeFrame: Week 52
measure: Percentage of Participants With Adverse Device Effects (ADEs)
timeFrame: Day 1 to Week 52
measure: Number of Participants with Anticipated Serious Adverse Device Effects (ASADEs) and Severity of ASADEs
timeFrame: Day 1 to Week 52
measure: Duration of ASADEs
timeFrame: Day 1 to Week 52
Other outcomes:
Locations:
city: Mesa
country: United States
facility: Barnet Dulaney Perkins Eye Center
state: Arizona
city: Bakersfield
country: United States
facility: California Retina Consultants
state: California
city: Huntington Beach
country: United States
facility: Retina Associates of Southern California
state: California
city: Pasadena
country: United States
facility: California Eye Specialists Medical group Inc.
state: California
city: Sacramento
country: United States
facility: Retinal Consultants Med Group
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Santa Ana
country: United States
facility: Orange County Retina Med Group
state: California
city: Torrance
country: United States
facility: Macula Retina Vitreous Research Institute
state: California
city: Durango
country: United States
facility: Southwest Retina Consultants
state: Colorado
city: Longmont
country: United States
facility: Advanced Vision Research Institute
state: Colorado
city: Waterford
country: United States
facility: Retina Group of New England
state: Connecticut
city: Pensacola
country: United States
facility: Retina Specialty Institute
state: Florida
city: Plantation
country: United States
facility: Ft Lauderdale Eye Institute
state: Florida
city: Saint Petersburg
country: United States
facility: Retina Vitreous Associates of Florida
state: Florida
city: Augusta
country: United States
facility: Southeast Retina Center
state: Georgia
city: Lemont
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: Lexington
country: United States
facility: Retina Associates of Kentucky
state: Kentucky
city: Portland
country: United States
facility: Maine Eye Center
state: Maine
city: Baltimore
country: United States
facility: The Retina Care Center
state: Maryland
city: Baltimore
country: United States
facility: Wilmer Eye Institute Johns Hopkins University
state: Maryland
city: Chevy Chase
country: United States
facility: Retina Group of Washington
state: Maryland
city: Hagerstown
country: United States
facility: Cumberland Valley Retina Consultants PC
state: Maryland
city: Royal Oak
country: United States
facility: Associated Retinal Consultants PC
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: Reno
country: United States
facility: Sierra Eye Associates
state: Nevada
city: Bloomfield
country: United States
facility: Envision Ocular, LLC
state: New Jersey
city: Poughkeepsie
country: United States
facility: Seeta Eye Centers
state: New York
city: Asheville
country: United States
facility: Western Carolina Retinal Associate PA
state: North Carolina
city: Durham
country: United States
facility: Duke Eye Center
state: North Carolina
city: Fargo
country: United States
facility: Fargo Retina Consultants
state: North Dakota
city: Blue Ash
country: United States
facility: Cincinnati Eye Institute
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Tulsa
country: United States
facility: Tulsa Retina Consultants
state: Oklahoma
city: Erie
country: United States
facility: Erie Retina Research
state: Pennsylvania
city: Philadelphia
country: United States
facility: Mid Atlantic Retina
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: Amarillo
country: United States
facility: Panhandle Eye Group LLP Southwest Retina Specialists
state: Texas
city: Austin
country: United States
facility: Austin Retina Associates
state: Texas
city: Bellaire
country: United States
facility: Retina Consultants of Texas
state: Texas
city: Schertz
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: Lynchburg
country: United States
facility: Piedmont Eye Center
state: Virginia
city: Norfolk
country: United States
facility: Wagner Kapoor Institute
state: Virginia
city: Richmond
country: United States
facility: Retina Institute of Virginia
state: Virginia
city: Spokane
country: United States
facility: Spokane Eye Clinical Research
state: Washington
Study officials:
affiliation: Genetech
name: Clinical Trials
role: STUDY_DIRECTOR
References: