Neovascular Age-related Macular DegenerationPhase 4BelvedereNCT04853251
A Study Assessing Corneal Endothelial Cells in Participants With Neovascular Age-related Macular Degeneration (nAMD) Treated With the Port Delivery System With Ranibizumab (PDS)
A Phase 4 study testing PDS Implant With Ranibizumab 100 mg/ml and LUCENTIS (Ranibizumab Injection) in people with Neovascular Age-related Macular Degeneration, run by Genentech, Inc. at 52 sites in United States.
Trial summary
This study will assess corneal endothelial cells in participants with nAMD treated with PDS refilled every 24 weeks (Q24W). Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Neovascular Age-related Macular Degeneration
- What is being tested?
- PDS Implant With Ranibizumab 100 mg/ml and LUCENTIS (Ranibizumab Injection)
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 188 participants
- Where
- 52 sitesUnited States
- Study dates
- 14 Dec 2021to 31 Aug 2027
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ocular Inclusion Criteria:
- Diagnosis of nAMD prior to screening as determined by the investigator
- 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). Additionally, fluorescein angiography or color fundus photography can both be used to support participant eligibility per protocol at investigator discretion
- Availability of comprehensive historical anti-vascular endothelial growth factor (VEGF) injection data, including agent administered and date of administration from the time of diagnosis, or for at least 2 years prior to screening if diagnosis was made more than 2 years before screening
- Response to at least two prior anti-VEGF IVT injections as determined by the investigator based on the following:
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- Overall decrease in nAMD disease activity detected on historical or screening OCT
- Stable or improved best-corrected visual acuity (BCVA)
- 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
- 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
Who cannot join
- Prior Ocular Treatment
- Study Eye:
- Prior treatment with external-beam radiation therapy or transpupillary thermotherapy
- Previous treatment with verteporfin injection (PDT) or corticosteroid IVT injection within 2 years of screening
- Previous laser (except PDT as stated above) used for age related macular degeneration (AMD) treatment
- History of corneal transplant
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- History of conjunctival surgery in the superotemporal quadrant
- History of intraocular inflammation following anti-VEGF injection
- Either Eye:
- Previous PDS implantation
- Previous intraocular surgery (including cataract surgery) within 6 months of study enrollment
- Prior vitrectomy surgery, submacular surgery, or other surgical intervention for age-related macular degeneration (AMD)
- Prior pars plana vitrectomy surgery
- Previous intraocular device implantation, excluding intraocular lenses
- History of glaucoma-filtering surgery, tube shunts, or microinvasive glaucoma surgery
- Prior participation in a clinical trial involving any intravitreal agents that are not approved at time of screening
- 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 penetrating ocular trauma
- Any prior ocular blunt trauma affecting corneal or retinal health in the opinion of the investigator, or any ocular blunt trauma within 6 months of screening
- History of corneal transplantation, including partial-thickness corneal grafts
- Prior treatment with brolucizumab
- Prior treatment with external-beam radiation therapy or brachytherapy
- History of hypersensitivity to ranibizumab or any excipients of Susvimo
- 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 millimeters (mm^2)] in size
- Subfoveal fibrosis or subfoveal atrophy
- Either Eye:
- MNV due to other causes, such as ocular histoplasmosis, trauma, or pathologic myopia
- MNV masquerading lesions (e.g., cone dystrophy, adult vitelliform dystrophy, pattern dystrophy)
- Current or Historical 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
- Current vitreous hemorrhage
- Current or history of retinal detachment
- 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 examination
- 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 and any such condition the investigator determines may require a glaucoma-filtering surgery during a patient's participation in the study
- 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 or history of 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 intraocular inflammation
- 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:
- History of uncontrolled blood pressure
- Active or history of autoimmune diseases such as rheumatoid arthritis, lupus, granulomatosis with polyangiitis (Wegener's)
- 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
- Requirement for continuous use of any medications or treatments indicated as prohibited therapy
- 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
Trial locations and contacts
52 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Reference Study ID Number: ML43000 https://forpatients.roche.com/ No attachments to email below. contact
Fastest response: use the inquiry form. No email attachments. https://www.gene.com/contact-us/submit-medical-inquiry contact
52 sites in 1 country
United States52 sites, 2 recruiting
- Completed
Panhandle Eye Group LLP Southwest Retina Specialists
Amarillo, Texas, 79106-1835
- Withdrawn
Western Carolina Retinal Associate PA
Asheville, North Carolina, 28803-2493
- Active, not recruiting
Southeast Retina Center
Augusta, Georgia, 30909-6440
- Withdrawn
Austin Retina Associates
Austin, Texas, 78705-1169
- Recruiting
Austin Clinical Research, LLC
Austin, Texas, 78750-2298
- Completed
California Retina Consultants
Bakersfield, California, 93309
- Active, not recruiting
The Retina Care Center
Baltimore, Maryland, 21209-2219
- Active, not recruiting
Wilmer Eye Institute Johns Hopkins University
Baltimore, Maryland, 21287-0005
- Active, not recruiting
Retina Consultants of Texas
Bellaire, Texas, 77401
- Active, not recruiting
Envision Ocular, LLC
Bloomfield, New Jersey, 07003
- Active, not recruiting
Cincinnati Eye Institute
Blue Ash, Ohio, 45242-5537
- Completed
Midwest Vision Research Foundation
Chesterfield, Missouri, 63017-5065
- Withdrawn
Retina Group of Washington
Chevy Chase, Maryland, 20815-6956
- Active, not recruiting
Cleveland Clinic
Cleveland, Ohio, 44195
- Completed
Southwest Retina Consultants
Durango, Colorado, 81303
- Active, not recruiting
Duke Eye Center
Durham, North Carolina, 27705-4699
- Completed
Erie Retina Research
Erie, Pennsylvania, 16505
- Active, not recruiting
Fargo Retina Consultants
Fargo, North Dakota, 58047
- Withdrawn
Palmetto Retina Center
Florence, South Carolina, 29501
- Active, not recruiting
Charles Retina Institute
Germantown, Tennessee, 38138-2405
- Completed
Cumberland Valley Retina Consultants PC
Hagerstown, Maryland, 21740
- Recruiting
Graystone Eye-Hickory - 2415 Century Pl
Hickory, North Carolina, 28602
- Active, not recruiting
Retina Associates of Southern California
Huntington Beach, California, 92647
- Active, not recruiting
University Retina and Macula Associates, PC
Lemont, Illinois, 60439-7421
- Withdrawn
Retina Associates of Kentucky
Lexington, Kentucky, 40509-1827
- Active, not recruiting
Advanced Vision Research Institute
Longmont, Colorado, 80503-6499
- Active, not recruiting
Piedmont Eye Center
Lynchburg, Virginia, 24502-4271
- Active, not recruiting
Barnet Dulaney Perkins Eye Center
Mesa, Arizona, 85206-2747
- Active, not recruiting
VitreoRetinal Surgery, PLLC.
Minneapolis, Minnesota, 55435-3004
- Active, not recruiting
Tennessee Retina PC
Nashville, Tennessee, 37203-1596
- Active, not recruiting
Wagner Kapoor Institute
Norfolk, Virginia, 23502-3933
- Completed
California Eye Specialists Medical group Inc.
Pasadena, California, 91107-3747
- Active, not recruiting
Retina Specialty Institute
Pensacola, Florida, 32503-2030
- Withdrawn
Mid Atlantic Retina
Philadelphia, Pennsylvania, 19107-5109
- Withdrawn
Ft Lauderdale Eye Institute
Plantation, Florida, 33324-3118
- Active, not recruiting
Maine Eye Center
Portland, Maine, 04101
- Active, not recruiting
Seeta Eye Centers
Poughkeepsie, New York, 12603-2416
- Active, not recruiting
Sierra Eye Associates
Reno, Nevada, 89502-1605
- Withdrawn
Retina Institute of Virginia
Richmond, Virginia, 23235-1962
- Active, not recruiting
Associated Retinal Consultants PC
Royal Oak, Michigan, 48073
- Active, not recruiting
Retinal Consultants Med Group
Sacramento, California, 95841-2013
- Active, not recruiting
Retina Associates of Utah, PLLC
Salt Lake City, Utah, 84107-6767
- Active, not recruiting
University of California San Francisco
San Francisco, California, 94158-2510
- Active, not recruiting
Orange County Retina Med Group
Santa Ana, California, 92705-6504
- Active, not recruiting
Retina Consultants of Texas
Schertz, Texas, 78154
- Active, not recruiting
Spokane Eye Clinical Research
Spokane, Washington, 99204-2509
- Active, not recruiting
Retina Vitreous Associates of Florida
St. Petersburg, Florida, 33711-1141
- Active, not recruiting
Macula Retina Vitreous Research Institute
Torrance, California, 90503-3270
- Withdrawn
Tulsa Retina Consultants
Tulsa, Oklahoma, 74114
- Withdrawn
Retina Group of New England
Waterford, Connecticut, 06385-1215
- Withdrawn
Palmetto Retina Center, LLC
West Columbia, South Carolina, 29169-2429
- Withdrawn
Wolfe Eye Clinic
West Des Moines, Iowa, 50266
About this study
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)
This study will assess corneal endothelial cells in participants with nAMD treated with PDS refilled every 24 weeks (Q24W).
- Being tested
- PDS Implant With Ranibizumab 100 mg/ml, LUCENTIS (Ranibizumab Injection)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PDS Implant With Ranibizumab 100 mg/mlDevice
Ranibizumab 100 mg/mL will be delivered via PDS
LUCENTIS (Ranibizumab Injection)Drug
Ranibizumab (0.5 mg intravitreal [IVT] injections of 10 mg/mL formulation) will be used in the study eye as supplemental treatment. If a participant discontinues study treatment, he/she may start receiving IVT ranibizumab injections in the study eye, per investigator's discretion.
| Study group | Role | What they receive |
|---|---|---|
| SUSVIMO | Experimental | Participants will have the PDS implant (filled prior to implantation with approximately 20 microlitres [uL] of the 100 milligrams/millilitres [mg/ml] formulation of ranibizumab [approximately 2 milligrams (mg) dose of ranibizumab]) surgically inserted in the study eye at the Day 1 visit following their enrollment visit. After the initial fill of the implant with ranibizumab, participants will receive implant refill-exchanges at fixed Q24W intervals. Receives: Device: PDS Implant With Ranibizumab 100 mg/ml; Drug: LUCENTIS (Ranibizumab Injection) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Baseline, Week 48
Secondary outcomes (12)
Percent Change in Corneal ECD From Baseline at Week 24 in the Study Eye as Compared With the Fellow Eye
Measured: Baseline, Week 24
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
Measured: Baseline, Week 24, Week 48
Percent Change in Hexagonal Cells (HEX) From Baseline at Weeks 24 and 48 in the Study Eye as Compared With the Fellow Eye
Measured: Baseline, Week 24, Week 48
Percentage of Participants With Ocular Serious Adverse Events (SAEs) and Severity of SAEs
Measured: Day 1 up to approximately Week 52
Percentage of Participants With Ocular Adverse Events of Special Interests (AESIs) and Severity of Ocular AESIs
Measured: Day 1 to Week 52
Duration of Ocular AESIs
Measured: Day 1 to Week 52
Percentage of Participants With Ocular AESIs During the Postoperative Period
Measured: Baseline up to 37 days of initial implantation
Percentage of Participants With Ocular AESIs During the Intermediate Postoperative Period
Measured: 38 to 93 days after implantation
Percentage of Participants With Ocular AESIs During the Follow-up Period
The investigator will follow each adverse event (AE) until the event has resolved to baseline grade or better, the event is assessed as stable by the investigator, the participant is lost to follow-up, or the participant withdraws consent.
Measured: Week 52
Percentage of Participants With Adverse Device Effects (ADEs)
Measured: Day 1 to Week 52
Number of Participants with Anticipated Serious Adverse Device Effects (ASADEs) and Severity of ASADEs
Measured: Day 1 to Week 52
Duration of ASADEs
Measured: Day 1 to Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2021
- Study start14 Dec 2021
- Primary completion30 Jul 2027 (estimated)
- Study completion31 Aug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neovascular Age-related Macular DegenerationStudies of the same condition, open and under way.
- More trials run by Genentech, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 188 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Genentech, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Genentech, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04853251
- Sponsor's protocol ID
- ML43000
- Acronym
- Belvedere
- Status last verified
- Oct 2026
- First submitted
- 16 Apr 2021
- Last updated
- 2 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data\_sharing