Study of Zifibancimig in Participants With Neovascular Age-Related Macular Degeneration
- Conditions
- Macular Degeneration
- Interventions
- Registration Number
- NCT04567303
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This is a first in-human study to investigate the safety, tolerability and efficacy of zifibancimig administered through intravitreal (IVT) injections and via the Port Delivery (PD) implant in participants with neovascular age-related macular degeneration (nAMD)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 251
- Willing to allow AH collection.
Part 1 and Part 2 Ocular Inclusion Criteria for Study Eye:
- Choroidal neovascularization (CNV) exclusively due to age-related macular degeneration (AMD).
- Anti-vascular endothelial growth factor (VEGF) or anti-VEGF/Angiopoietin-2 (Ang-2) IVT treatment-naïve, or pre-treated with anti-VEGF or anti-VEGF/Ang-2 no less than two months prior to Day 1.
- Sufficiently clear ocular media and adequate pupillary dilatation to allow for analysis and grading by the central reading center of fundus photography (FP), fluorescein angiography (FA), fundus autofluorescence (FAF), and spectral domain optical coherence tomography (SD-OCT) images.
- Decreased BCVA attributable primarily to nAMD, with BCVA letter score of 78 to 34 letters (inclusive) on ETDRS-like charts at screening. In case both eyes of a participant are eligible, the eye with the lower BCVA score should become the study eye.
Part 3 Ocular Inclusion Criteria for Study Eye:
- CNV exclusively due to AMD.
- Diagnosis of nAMD within 36-months prior to the screening visit.
- Previous treatment with at least one IVT anti-VEGF or anti-VEGF/Ang-2 administrations IVT for nAMD. The last IVT administration must have occurred at least 21 days prior to the screening visit.
- Demonstrated response to prior IVT anti-VEGF or anti-VEGF/Ang-2 treatment since diagnosis.
- Availability of historical VA data prior to the first anti-VEGF or anti-VEGF/Ang-2 treatment for nAMD.
- Sufficiently clear ocular media and adequate pupillary dilatation to allow for analysis and grading.
- Decreased BCVA attributable primarily to nAMD with letter score of 78 to 34 letters (inclusive) or better on ETDRS-like charts.
Ocular Exclusion Criteria for Study Eye:
- History of vitrectomy surgery, submacular surgery, other intraocular surgery, or any planned surgical intervention during the study period.
- Cataract surgery without complications within three months preceding the screening visit or planned during the study period.
- 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 laser posterior capsulotomy in association with prior, posterior chamber intraocular lens implantation.
- Prior macular treatment with verteporfin, external beam radiation therapy, transpupillary thermotherapy, or any type of laser photocoagulation.
- Prior treatment with IVT corticosteroids or implant (e.g., triamcinolone, ozurdex, iluvien).
- Subretinal hemorrhage >50% of the total lesion area and/or involving the fovea.
- Subfoveal fibrosis or subfoveal atrophy.
- Retinal pigment epithelial tear involving the macula.
- History of vitreous hemorrhage, rhegmatogenous retinal detachment, glaucoma-filtering surgery, tube shunts, or microinvasive glaucoma surgery, and corneal transplant.
- History of rhegmatogenous retinal tears or peripheral retinal breaks within three months prior to the screening visit.
- Actual or history of myopia >-8 diopters.
- Uncontrolled ocular hypertension or glaucoma (defined as intraocular pressure (IOP) >25 millimeters of mercury (mm Hg) or a cup to disc ration >0.8, despite treatment with antiglaucoma medication) and any such condition the Investigator determines may require a glaucoma-filtering surgery during a participant's participation in the study.
- Concurrent intraocular conditions (e.g., cataract, diabetic retinopathy, epiretinal membrane with traction, macular hole) that, in the opinion of the Investigator, could either:
- Require medical or surgical intervention during the study period to prevent or treat visual loss that might result from that condition; or
- Likely contribute to loss of BCVA over the study period if allowed to progress untreated; or
- Preclude any visual improvement due to substantial structural damage.
- Concurrent conjunctival, Tenon's capsule, and/or scleral condition in the supero-temporal quadrant of the eye (e.g., scarring, thinning, mass) that may affect the implantation, subsequent tissue coverage, and refill-exchange procedure of the PD implant.
- Prior treatment with any medication for geographic atrophy during the last 3 months prior to screening.
- Prior treatment with any anti-VEGF-C or anti-VEGF-D inhibitors.
Exclusion Criteria for Fellow Eye
- BCVA letter score using ETDRS charts of < 34 letters.
- Treatment with IVT anti-VEGF or anti-VEGF/Ang-2 agents within one week prior to Day 1 (concurrent treatment with SUSVIMO^TM in the fellow eye is not exclusionary).
Exclusion Criteria for Either Eye
- CNV due to causes other than nAMD, such as ocular histoplasmosis, trauma, pathological myopia, angioid streaks, choroidal rupture, uveitis or central serous chorioretinopathy.
- Prior participation in a clinical trial involving anti-VEGF drugs within six months prior to the screening visit, other than ranibizumab, aflibercept, or faricimab including approved biosimilars.
- Active intraocular inflammation (grade trace or above), infectious conjunctivitis, keratitis, scleritis, or endophthalmitis.
- History of uveitis, including history of any intraocular inflammation following intravitreal therapy.
- Prior treatment with brolucizumab.
- Prior gene therapy for nAMD
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 3: Port Delivery with Low Dose Zifibancimig Zifibancimig administered at a low dose through the PD implant. Part 2: Port Delivery with High Dose Port Delivery Platform Zifibancimig administered at a high dose through the PD implant. Part 2: Port Delivery with Low Dose Port Delivery Platform Zifibancimig administered at a low dose through the PD implant. Part 3: Port Delivery with High Dose Port Delivery Platform Zifibancimig administered at a high dose through the PD implant. Part 3: Port Delivery with Low Dose Port Delivery Platform Zifibancimig administered at a low dose through the PD implant. Part 3: Port Delivery with Ranibizumab Ranibizumab 100 milligrams/milliliter (mg/mL) of ranibizumab administered through the PD implant. Part 3: Port Delivery with Ranibizumab Port Delivery Platform 100 milligrams/milliliter (mg/mL) of ranibizumab administered through the PD implant. Part 1: Intravitreal Injections Zifibancimig Zifibancimig administered in ascending dose levels through IVT injections. Part 2: Port Delivery with High Dose Zifibancimig Zifibancimig administered at a high dose through the PD implant. Part 2: Port Delivery with Low Dose Zifibancimig Zifibancimig administered at a low dose through the PD implant. Part 3: Port Delivery with High Dose Zifibancimig Zifibancimig administered at a high dose through the PD implant.
- Primary Outcome Measures
Name Time Method Duration of ASADEs Part 2: Baseline up to Week 48; Part 3: Baseline up to Week 48 Change from Baseline in Early Treatment Diabetic Retinopathy Study - Best Corrected Visual Acuity (ETDRS-BCVA) Score Part 3: Baseline (baseline visit, before implant insertion) to Week 48 ETDRS-BCVA will be used to quantify visual acuity. BCVA is measured using an eye chart and is reported as the number of letters read correctly using the ETDRS Scale (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved.
Percentage of Participants with Ocular and Systemic (Nonocular) Adverse Events (AEs) Part 1: Baseline up to Week 24; Part 2: Baseline up to Week 48; Part 3: Baseline up to Week 48 Percentage of Participants with Ocular and Systemic (Nonocular) AEs during Post-operative and Follow-up Periods Part 2 and 3: From Day 1 to Week 4 and during follow up period (up to Week 48) Percentage of Participants with Adverse Events of Special Interest (AESIs) including Ocular AESIs Part 1: Baseline up to Week 24; Part 2: Baseline up to Week 48; Part 3: Baseline up to Week 48 Percentage of Participants with AESIs including Ocular AESIs during the Postoperative and Follow-up periods Part 2 and 3: From Day 1 to Week 4 and during follow up period (up to Week 48) Duration of AESIs including Ocular AESIs Part 1: Baseline up to Week 24; Part 2: Baseline up to Week 48; Part 3: Baseline up to Week 48 Duration of AESIs including Ocular AESIs during the Postoperative and Follow-up periods Part 2 and 3: From Day 1 to Week 4 and during follow up period (up to Week 48) Percentage of Participants with Adverse Device Effects (ADEs) Part 2: Baseline up to Week 48; Part 3: Baseline up to Week 48 Duration of ADEs Part 2: Baseline up to Week 48; Part 3: Baseline up to Week 48 Percentage of Participants with Anticipated Serious ADEs (ASADEs) Part 2: Baseline up to Week 48; Part 3: Baseline up to Week 48
- Secondary Outcome Measures
Name Time Method Time of Maximum Concentration Observed (Tmax) of Zifibancimig in Blood and AH Part 1: Baseline up to Week 24; Part 2: Baseline up to Week 144; Part 3: Baseline up to Week 144 Percentage of Participants who did not meet Supplemental Treatment Criteria for the PD implant with Zifibancimig Part 3: Week 36, Week 40, and Week 44 Change from Baseline in Central Subfield Thickness (CST) Part 3: Baseline to Week 48 Area Under the Curve (AUC) of Zifibancimig in Blood and AH Part 1: Baseline up to Week 24; Part 2: Baseline up to Week 144; Part 3: Baseline up to Week 144 Maximum Observed Concentration (Cmax) of Zifibancimig in Blood and Aqueous Humor (AH) Part 1: Baseline up to Week 24; Part 2: Baseline up to Week 144; Part 3: Baseline up to Week 144 Concentration at the End of a Dosing Interval before the Next Dose Administration (Ctrough) of Zifibancimig in Blood and AH Part 1: Baseline up to Week 24; Part 2: Baseline up to Week 144; Part 3: Baseline up to Week 144 Percentage of Participants who Gained or Lost ≥15, ≥10 ≥5 or ≥0 letters in ETDRS-BCVA score from Baseline Part 3: Baseline to Week 48 ETDRS-BCVA will be used to quantify visual acuity. BCVA is measured using an eye chart and is reported as the number of letters read correctly using the ETDRS Scale (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved.
Change from Baseline Over Time in CST Part 3: Baseline to end of follow up period (up to Week 144)
Trial Locations
- Locations (46)
Barnet Dulaney Perkins Eye Center
🇺🇸Mesa, Arizona, United States
Associated Retina Consultants
🇺🇸Phoenix, Arizona, United States
The Retina Partners
🇺🇸Encino, California, United States
Retinal Consultants Med Group
🇺🇸Sacramento, California, United States
Orange County Retina Med Group
🇺🇸Santa Ana, California, United States
Southern Vitreoretinal Assoc
🇺🇸Tallahassee, Florida, United States
Southeast Retina Center
🇺🇸Augusta, Georgia, United States
University Retina and Macula Associates, PC
🇺🇸Oak Forest, Illinois, United States
West Coast Retina Medical Group
🇺🇸San Francisco, California, United States
Retina Specialty Institute
🇺🇸Pensacola, Florida, United States
Southwest Retina Consultants
🇺🇸Durango, Colorado, United States
The Retina Care Center
🇺🇸Baltimore, Maryland, United States
Retina Vitreous Assoc of FL
🇺🇸Saint Petersburg, Florida, United States
Retina Associates of Florida, LLC
🇺🇸Tampa, Florida, United States
Maine Eye Center
🇺🇸Portland, Maine, United States
Johns Hopkins Med
🇺🇸Baltimore, Maryland, United States
Retina Group of Washington
🇺🇸Chevy Chase, Maryland, United States
Cumberland Valley Retina Consultants
🇺🇸Hagerstown, Maryland, United States
Foundation for Vision Research
🇺🇸Grand Rapids, Michigan, United States
Associated Retinal Consultants
🇺🇸Royal Oak, Michigan, United States
VitreoRetinal Surgery, PLLC.
🇺🇸Edina, Minnesota, United States
Midwest Vision Research Foundation
🇺🇸Chesterfield, Missouri, United States
The Retina Institute
🇺🇸Saint Louis, Missouri, United States
Sierra Eye Associates
🇺🇸Reno, Nevada, United States
Envision Ocular, LLC
🇺🇸Bloomfield, New Jersey, United States
Long Is. Vitreoretinal Consult
🇺🇸Hauppauge, New York, United States
Retina Vit Surgeons/Central NY
🇺🇸Liverpool, New York, United States
Graystone Eye
🇺🇸Hickory, North Carolina, United States
The Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
OSU Eye Physicians & Surgeons
🇺🇸Columbus, Ohio, United States
Mid Atlantic Retina - Wills Eye Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Charleston Neuroscience Inst
🇺🇸Ladson, South Carolina, United States
Charles Retina Institute
🇺🇸Germantown, Tennessee, United States
Southeastern Retina Associates
🇺🇸Knoxville, Tennessee, United States
Tennessee Retina PC.
🇺🇸Nashville, Tennessee, United States
Retina Res Institute of Texas
🇺🇸Abilene, Texas, United States
Austin Research Center for Retina
🇺🇸Austin, Texas, United States
Austin Clinical Research LLC
🇺🇸Austin, Texas, United States
Retina & Vitreous of Texas
🇺🇸Bellaire, Texas, United States
Retina Consultants of Texas
🇺🇸Houston, Texas, United States
Brown Retina Institute
🇺🇸San Antonio, Texas, United States
Retina Center of Texas
🇺🇸Southlake, Texas, United States
Piedmont Eye Center
🇺🇸Lynchburg, Virginia, United States
Wagner Kapoor Institute
🇺🇸Norfolk, Virginia, United States
Spokane Eye Clinical Research
🇺🇸Spokane, Washington, United States
Emanuelli Research and Development Center LLC
🇵🇷Arecibo, Puerto Rico