A Study Assessing Corneal Endothelial Cells in Patients With Neovascular Age-related Macular Degeneration Treated With the Port Delivery System With Ranibizumab (PDS)

Neovascular Age-related Macular Degeneration Clinical Trial

— Belvedere  

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04853251
• Other study ID #: ML43000
• Status: Recruiting
• Phase: Phase 4
• Start date: December 14, 2021
• Est. completion date: April 30, 2027

Study information

• Verified date: January 2024
• Source: Genentech, Inc.
• Contact: Reference Study ID Number: ML43000 https://forpatients.roche.com
• Phone: 888-662-6728 (U.S.)
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will assess corneal endothelial cells in patients with neovascular age-related macular degeneration (nAMD) treated with Port Delivery System with ranibizumab (PDS) refilled every 24 weeks (Q24W)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 185
• Est. completion date: April 30, 2027
• Est. primary completion date: April 30, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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 data and SD-OCT imaging prior to the first anti-VEGF 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 intravitreal injections since diagnosis

• BCVA of 34 letters (approximate 20/200 Snellen equivalent) or better, using 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 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 intravitreal injection

• Previous laser (any type) used for AMD treatment

• History of vitreous hemorrhage

• History of rhegmatogenous retinal detachment

• History of corneal transplant

• History of conjunctival surgery in the superotemporal quadrant

• History of conjunctival surgery in the superotemporal quadrant

• Prior participation in a clinical trial involving any intravitreal anti-VEGF agents

• Prior participation in a clinical trial involving any intravitreal anti-VEGF agents

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

• 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 Characteristics

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

• 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 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

• Retinal tears or peripheral retinal breaks on depressed fundus exam that are untreated, or treated within the 3 months prior to study enrollment

• 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 or evidence of pathologic myopia on depressed fundus exam

• Preoperative refractive error that exceeds 8 diopters of myopia, for patients 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 patients 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

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.

Related Conditions & MeSH terms

• Macular Degeneration
• Neovascular Age-related Macular Degeneration
• Wet Macular Degeneration

Intervention

Device:
• SUSVIMO Port Delivery System with ranibizumab (PDS)
The ranibizumab 100 mg/mL will be delivered via the Port Delivery System

Drug:
• LUCENTIS (ranibizumab injection)
Ranibizumab (intravitreal 0.5-mg intravitreal injections of 10 mg/mL formulation) will be used in the study eye as supplemental treatment. If a study patient discontinues study treatment, he/she may start receiving intravitreal ranibizumab injections in the study eye, per investigator's discretion.

Locations

Country	Name	City	State
United States	Western Carolina Retinal Associate PA	Asheville	North Carolina
United States	Southeast Retina Center	Augusta	Georgia
United States	Austin Retina Associates	Austin	Texas
United States	California Retina Consultants	Bakersfield	California
United States	The Retina Care Center	Baltimore	Maryland
United States	Wilmer Eye Institute Johns Hopkins University	Baltimore	Maryland
United States	Mid Atlantic Retina	Cherry Hill	New Jersey
United States	Midwest Vision Research Foundation	Chesterfield	Missouri
United States	Retina Group of Washington	Chevy Chase	Maryland
United States	Cincinnati Eye Institute	Cincinnati	Ohio
United States	Southwest Retina Consultants	Durango	Colorado
United States	VitreoRetinal Surgery, PLLC.; DBA Retina Consultants of Minnesota	Edina	Minnesota
United States	Cumberland Valley Retina Consultants	Hagerstown	Maryland
United States	Retina Associates of Kentucky	Lexington	Kentucky
United States	Piedmont Eye Center	Lynchburg	Virginia
United States	Barnet Dulaney Perkins Eye Center	Mesa	Arizona
United States	Ft Lauderdale Eye Institute	Miami Lakes	Florida
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	California Eye Specialists Medical group Inc.	Pasadena	California
United States	Retina Specialty Institute	Pensacola	Florida
United States	Sierra Eye Associates	Reno	Nevada
United States	Retina Institute of Virginia	Richmond	Virginia
United States	Associated Retinal Consultants PC	Royal Oak	Michigan
United States	Retinal Consultants Med Group	Sacramento	California
United States	Retina Vitreous Associates of Florida	Saint Petersburg	Florida
United States	Retina Associates of Utah, PLLC	Salt Lake City	Utah
United States	Orange County Retina Med Group	Santa Ana	California
United States	Retina Consultants of Texas	The Woodlands	Texas
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
Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent change in corneal ECD from baseline at Week 48 in the study eye as compared with the fellow eye, as assessed by specular microscopy		Baseline up to Week 48
Secondary	Percent change in corneal ECD from baseline at Week 24 in the study eye as compared with the fellow eye		Baseline up to Week 24
Secondary	Percent change in the CV of corneal endothelial cell area (standard deviation of the cell area/mean cell area) from baseline at Weeks 24 and 48 in the study eye as compared with the fellow eye		Baseline, Week 24, Week 48
Secondary	Percent change in HEX from baseline at Weeks 24 and 48 in the study eye as compared with the fellow eye		Baseline, Week 24, Week 48
Secondary	Percentage of participants with ocular serious adverse events (SAEs)		Day 1 up to approximately Week 52
Secondary	Percentage of participants with ocular adverse events of special interest (AESIs)		Day 1 to Week 52
Secondary	Percentage of participants with adverse device effects (ADEs) in the course of the study		Day 1 to Week 52
Secondary	Percentage of participants with ocular AESIs during the postoperative period		Baseline up to 37 days of initial implantation
Secondary	Percentage of participants with ocular AESIs during the intermediate postoperative period		38 to 93 days after implantation
Secondary	Percentage of participants with ocular AESIs during the follow-up period	The investigator will follow each adverse event until the event has resolved to baseline grade or better, the event is assessed as stable by the investigator, the patient is lost to follow-up, or the patient withdraws consent.	Week 52