A clinical trial to evaluate maintenance of vision after switching to treatment with an eye implant containing ranibizumab in participants with neovascular age-related macular degeneration

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

  • Eye Disorder
  • Neovascular Age-related Macular Degeneration
Please note that the recruitment status of the trial at your site may differ from the overall study status because some study sites may recruit earlier than others.
Trial Status:

Recruiting

This trial runs in
Country
  • United States
Trial Identifier:

NCT04853251 ML43000

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      The source of the below information is public registry websites such as ClinicalTrials.gov, EuClinicalTrials.eu, ISRCTN.com, etc.. It has been summarised and edited into simpler language. For more information about this clinical trial see the For Expert tab on the specific ForPatients page or follow these links to https://clinicaltrials.gov and/or https://euclinicaltrials.eu and/or https://www.isrctn.com.

      The below information is taken directly from public registry websites such as ClinicalTrials.gov, EuClinicalTrials.eu, ISRCTN.com, etc., and has not been edited.

      Results Disclaimer

      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)

      Genentech, Inc. Sponsor
      Phase 4 Phase
      NCT04853251,ML43000 Trial Identifier
      All Gender
      ≥50 Years Age
      No Healthy Volunteers

      1. Why is the Belvedere clinical trial needed?

      Age-related macular degeneration (AMD) is a condition that causes blurred or reduced central vision in one or both eyes. There are two forms of AMD depending on how the back of the eye (known as the macula) is damaged, ‘dry AMD’ and ‘neovascular AMD’ (also called wet AMD). In wet AMD, a chemical produced by the body called vascular endothelial growth factor (VEGF) causes abnormal blood vessels to be formed in the eye that can leak fluid onto the back of the eye and affect vision.

      Wet AMD can be treated by injecting a type of drug called anti-VEGF (e.g. ranibizumab), into the eye (also known as an intravitreal injection). However, many people find anti-VEGF intravitreal injections burdensome, as they are given as often as every 1‒2 months. To reduce this burden, a refillable eye implant was designed that continuously releases ranibizumab over time, with refills of ranibizumab approximately every 6 months. This is called the port delivery system with ranibizumab. After testing in previous trials, the port delivery system with ranibizumab is now approved for the treatment of wet AMD.

      In this trial, researchers will assess how well vision is maintained in people who switch from a previous anti-VEGF treatment (other than ranibizumab) to the eye implant that contains ranibizumab. 

       

      2. How does the Belvedere clinical trial work?

      This clinical trial is recruiting people who have a health condition called wet AMD. People can take part if they have previously received treatment with at least three anti-VEGF intravitreal injections other than ranibizumab, within 9 months prior to Day 1 of the clinical trial.

      One eye will be chosen as the ‘study eye’, and all participants in this trial will receive the eye implant pre-filled with ranibizumab, in the study eye using a surgical procedure. The eye implant will be refilled with ranibizumab during clinic visits on Weeks 24 and 48. Participants will have approximately 11 in-person clinic visits, and these may last 2‒4 hours. These visits are to see how the participant is responding to the treatment and any side effects they may be having. Participants will also have approximately five clinical trial assessments by telephone or video call. Participants’ total time in the clinical trial will be roughly 1 year. Participants are free to stop trial treatment and leave the clinical trial at any time.

       

      3. What are the main endpoints of the Belvedere clinical trial?

      The main clinical trial endpoint (the main results that are measured in the trial) is to evaluate the maintenance of vision after treatment in the study eye at Week 40, which is measured using an eye chart at a starting distance of 4 metres.

      The other clinical trial endpoints include an assessment of the maintenance of vision in the study eye at Week 40 according to previous intravitreal treatments received, measurement of visual maintenance up to Week 52, and the number and seriousness of any side effects experienced by the participant during the trial. 

       

      4. Who can take part in this clinical trial?

      People can take part in this trial if they are at least 50 years old, have been diagnosed with wet AMD within the past 6‒18 months, and have previously been treated with at least three anti-VEGF intravitreal injections other than ranibizumab. 

      People may not be able to take part in this trial if they have had previous eye surgery (except for cataract surgery if done more than 6 months ago), or received certain treatments, have a history of certain other medical conditions, are pregnant or are planning to soon become pregnant, or are breastfeeding.

       

      5. What treatment will participants be given in this clinical trial? 

      This is an open-label trial, which means everyone involved, including the participants and the doctors, know which clinical trial treatment is being used. Everyone who joins this clinical trial will receive the eye implant (pre-filled with the clinical trial drug, ranibizumab) in the study eye. This procedure takes around 30 minutes. The eye implant will then be refilled with ranibizumab at Week 24 and Week 48, during a procedure in the clinical trial doctor’s clinic that takes typically less than 15 minutes.  

      If the treatment is not having the desired effect, participants may receive an extra intravitreal injection of ranibizumab at the clinical trial specified visits (Week 16 and Week 40 or possibly at Week 20 and Week 44).

       

      6. Are there any risks or benefits in taking part in this clinical trial?

      The safety or effectiveness of the clinical trial treatment or use may not be fully known at the time of the trial. Most trials involve some risks to the participant, although it may not be greater than the risks related to routine medical care or the natural progression of the health condition. Potential participants will be told about any risks and benefits of taking part in the clinical trial, as well as any additional procedures, tests, or assessments they will be asked to undergo. These will all be described in an informed consent document (a document that provides people with the information they need to make a decision to volunteer for a clinical trial). A potential participant should also discuss these with members of the research team and with their usual healthcare provider. Anyone interested in taking part in a clinical trial should know as much as possible about the trial and feel comfortable asking the research team any questions about the trial.

      Risks associated with the clinical trial drug (1) and device (2)

      Participants may have side effects (an unwanted effect of a drug or medical treatment) from the drug or device used in this clinical trial. Side effects can be mild to severe and even life-threatening, and can vary from person to person. 

      Ranibizumab given via an eye implant

      1. Participants will be told about the known side effects of the clinical trial drug, ranibizumab, when given with an eye implant device.
      2. Potential participants will be told about the known side effects of the procedures involved in inserting, filling, refilling and removing (if needed) the eye implant device, and where relevant, also potential side effects based on human and laboratory studies or knowledge of similar devices.

       

      Potential benefits associated with the Belvedere clinical trial

      Participants' health may or may not continue to improve from participation in the clinical trial, but the information that is collected may help other people who have a similar medical condition in the future.

      For more information about this clinical trial see the For Expert tab on the specific ForPatients page or follow this link to ClinicalTrials.gov: https://clinicaltrials.gov/ct2/show/NCT04853251

       

      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)

      Genentech, Inc. Sponsor
      Phase 4 Phase
      NCT04853251,ML43000 Trial Identifier
      SUSVIMO (ranibizumab injection), LUCENTIS (ranibizumab injection) Treatments
      Neovascular Age-related Macular Degeneration Condition
      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)

      Eligibility criteria

      All Gender
      ≥50 Years Age
      No Healthy Volunteers
      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.

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