Study of Zifibancimig in Participants With Neovascular Age-related Macular Degeneration (BURGUNDY)

A Three-part, Phase I/II Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Efficacy of Zifibancimig Following Intravitreal Administration of Multiple Ascending Doses and Continuous Delivery From the Port Delivery in Patients With Neovascular Age-related Macular Degeneration

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Macular Degeneration
• Intervention / Treatment: Device: Port Delivery Platform; Drug: Ranibizumab; Drug: Zifibancimig

• Study Type: Interventional
• Enrollment (Actual): 177
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Puerto Rico
  • Arecibo, Puerto Rico, 00612
    • Emanuelli Research and Development Center LLC
• United States
  • Arizona
    • Mesa, Arizona, United States, 85206
      • Barnet Dulaney Perkins Eye Center
    • Phoenix, Arizona, United States, 85020
      • Associated Retina Consultants
  • California
    • Encino, California, United States, 91436
      • The Retina Partners
    • Sacramento, California, United States, 95841
      • Retinal Consultants Med Group
    • Santa Ana, California, United States, 92705
      • Orange County Retina Med Group
  • Colorado
    • Durango, Colorado, United States, 81303
      • Southwest Retina Consultants
  • Florida
    • St. Petersburg, Florida, United States, 33711
      • Retina Vitreous Assoc of FL
    • Tallahassee, Florida, United States, 32308
      • Southern Vitreoretinal Assoc
    • Tampa, Florida, United States, 33609
      • Retina Associates of Florida, LLC
  • Georgia
    • Augusta, Georgia, United States, 30909
      • Southeast Retina Center
  • Illinois
    • Oak Forest, Illinois, United States, 60452
      • University Retina and Macula Associates, PC
  • Maine
    • Portland, Maine, United States, 04101
      • Maine Eye Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Med
    • Chevy Chase, Maryland, United States, 20815
      • Retina Group of Washington
    • Hagerstown, Maryland, United States, 21740
      • Cumberland Valley Retina Consultants
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Foundation for Vision Research
    • Royal Oak, Michigan, United States, 48073
      • Associated Retinal Consultants
  • Minnesota
    • Saint Louis Park, Minnesota, United States, 55416
      • VitreoRetinal Surgery, PLLC.
  • Missouri
    • St Louis, Missouri, United States, 63128
      • The Retina Institute
  • Nevada
    • Reno, Nevada, United States, 89502
      • Sierra Eye Associates
  • New Jersey
    • Bloomfield, New Jersey, United States, 07003
      • Envision Ocular, LLC
  • New York
    • Liverpool, New York, United States, 13088
      • Retina Vit Surgeons/Central NY
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke Eye Center
    • Hickory, North Carolina, United States, 28602
      • Graystone Eye
  • Ohio
    • Columbus, Ohio, United States, 43212
      • OSU Eye Physicians & Surgeons
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Mid Atlantic Retina - Wills Eye Hospital
  • South Carolina
    • Mt. Pleasant, South Carolina, United States, 29464
      • Carolina Eyecare Physicians
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Charles Retina Institute
    • Knoxville, Tennessee, United States, 37922
      • Southeastern Retina Associates
    • Nashville, Tennessee, United States, 37203
      • Tennessee Retina PC.
  • Texas
    • Austin, Texas, United States, 78750
      • Austin Clinical Research LLC
    • Austin, Texas, United States, 78705
      • Austin Research Center for Retina
    • Bellaire, Texas, United States, 77401
      • Retina Consultants of Texas
    • Houston, Texas, United States, 77030
      • Retina Consultants of Texas
    • Southlake, Texas, United States, 76092
      • Retina Center of Texas
  • Virginia
    • Lynchburg, Virginia, United States, 24502
      • Piedmont Eye Center
    • Norfolk, Virginia, United States, 23502
      • Wagner Kapoor Institute
  • Washington
    • Spokane, Washington, United States, 99204
      • Spokane Eye Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Part 1, Part 2 and Part 3

Inclusion Criteria:

• 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 ratio >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 (GA) 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: IVT Injections; Zifibancimig administered in multiple ascending dose levels through IVT injections.	Drug: Zifibancimig; Part 1: multiple ascending doses by IVT injection. Each participant will receive zifibancimig at a constant volume of 50 microliter (µL) in the study eye. Part 2: participants will be randomized to one of two dose levels of zifibancimig in the PD implant. Part 3: Participants will receive one of the two dose levels of zifibancimig in the PD implant.; Other Names: RO7250284
Active Comparator: Part 3: PD With Ranibizumab; 100 mg/mL of ranibizumab administered through the PD implant.	Drug: Ranibizumab; Participants will receive ranibizumab 100 mg/mL through the PD implant
Experimental: Part 2: PD With High Dose; Zifibancimig administered at a high dose through the PD implant, followed by ranibizumab, 100 milligrams per milliliter (mg/mL), administered through the PD implant.	Device: Port Delivery Platform; Participants will receive intraocular refillable device that is surgically inserted into the eye for continuous delivery of drugs into the vitreous.; Drug: Ranibizumab; Participants will receive ranibizumab 100 mg/mL through the PD implant; Drug: Zifibancimig; Part 1: multiple ascending doses by IVT injection. Each participant will receive zifibancimig at a constant volume of 50 microliter (µL) in the study eye. Part 2: participants will be randomized to one of two dose levels of zifibancimig in the PD implant. Part 3: Participants will receive one of the two dose levels of zifibancimig in the PD implant.; Other Names: RO7250284
Experimental: Part 2: PD With Low Dose; Zifibancimig administered at a low dose through the PD implant, followed by ranibizumab, 100 mg/mL, administered through the PD implant.	Device: Port Delivery Platform; Participants will receive intraocular refillable device that is surgically inserted into the eye for continuous delivery of drugs into the vitreous.; Drug: Ranibizumab; Participants will receive ranibizumab 100 mg/mL through the PD implant; Drug: Zifibancimig; Part 1: multiple ascending doses by IVT injection. Each participant will receive zifibancimig at a constant volume of 50 microliter (µL) in the study eye. Part 2: participants will be randomized to one of two dose levels of zifibancimig in the PD implant. Part 3: Participants will receive one of the two dose levels of zifibancimig in the PD implant.; Other Names: RO7250284
Experimental: Part 3: PD With High Dose; Zifibancimig administered at a high dose through the PD implant, followed by ranibizumab, 100 mg/mL, administered through PD implant.	Device: Port Delivery Platform; Participants will receive intraocular refillable device that is surgically inserted into the eye for continuous delivery of drugs into the vitreous.; Drug: Ranibizumab; Participants will receive ranibizumab 100 mg/mL through the PD implant; Drug: Zifibancimig; Part 1: multiple ascending doses by IVT injection. Each participant will receive zifibancimig at a constant volume of 50 microliter (µL) in the study eye. Part 2: participants will be randomized to one of two dose levels of zifibancimig in the PD implant. Part 3: Participants will receive one of the two dose levels of zifibancimig in the PD implant.; Other Names: RO7250284
Experimental: Part 3: PD With Low Dose; Zifibancimig administered at a low dose through the PD implant, followed by ranibizumab, 100 mg/mL, administered through PD implant.	Device: Port Delivery Platform; Participants will receive intraocular refillable device that is surgically inserted into the eye for continuous delivery of drugs into the vitreous.; Drug: Ranibizumab; Participants will receive ranibizumab 100 mg/mL through the PD implant; Drug: Zifibancimig; Part 1: multiple ascending doses by IVT injection. Each participant will receive zifibancimig at a constant volume of 50 microliter (µL) in the study eye. Part 2: participants will be randomized to one of two dose levels of zifibancimig in the PD implant. Part 3: Participants will receive one of the two dose levels of zifibancimig in the PD implant.; Other Names: RO7250284

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Adverse Events of Special Interest (AESIs) Including Ocular AESIs		Part 1: Baseline up to Week 24; Parts 2 and 3: Baseline up to Week 48
Duration of Ocular AESIs		Part 1: Baseline up to Week 24; Parts 2 and 3: Baseline up to Week 48
Percentage of Participants With Adverse Device Effects (ADEs)		Parts 2 and 3: Baseline up to Week 48
Duration of ADEs		Parts 2 and 3: Baseline up to Week 48
Percentage of Participants With Anticipated Serious ADEs (ASADEs)		Parts 2 and 3: Baseline up to Week 48
Duration of ASADEs		Parts 2 and 3: Baseline up to Week 48
Percentage of Participants With Ocular and Systemic (Non-ocular) Adverse Events (AEs)		Part 1: Baseline up to Week 24; Parts 2 & 3: Baseline up to Week 48
Percentage of Participants With Ocular AEs During the Post-operative and Follow-up Periods		Parts 2 and 3: From Day 1 to Week 4 and during follow-up period (up to Week 48)
Percentage of Participants With Ocular AESIs During the Post-operative and Follow-up Periods		Parts 2 and 3: From Day 1 to Week 4 and during follow-up period (up to Week 48)
Duration of Ocular AESIs During the Post-operative and Follow-up Periods		Parts 2 and 3: From Day 1 to Week 4 and during follow-up period (up to Week 48)
Change From Baseline in Early Treatment Diabetic Retinopathy Study - Best Corrected Visual Acuity (ETDRS-BCVA) Score at 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.	Part 3: Baseline (baseline visit, before implant insertion), and Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Concentration (Cmax) of Zifibancimig in Blood and Aqueous Humor (AH)		Part 1: Baseline up to Week 24; Parts 2 and 3: Baseline up to Week 144
Time of Maximum Concentration Observed (Tmax) of Zifibancimig in Blood and AH		Part 1: Baseline up to Week 24; Parts 2 and 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; Parts 2 and 3: Baseline up to Week 144
Area Under the Curve (AUC) of Zifibancimig in Blood and AH		Part 1: Baseline up to Week 24; Parts 2 and 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 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.	Part 3: Baseline to Week 48
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) at Week 48		Part 3: Baseline, and Week 48
Change From Baseline Over Time in CST		Part 3: Baseline to end of follow-up period (up to Week 144)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): October 28, 2020
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: September 24, 2020
• First Submitted That Met QC Criteria: September 24, 2020
• First Posted (Actual): September 28, 2020

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Diseases; Retinal Degeneration; Macular Degeneration; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Ranibizumab
• Other Study ID Numbers: BP41670

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes