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

NCT ID: NCT04567303

Last Updated: 2026-01-12

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 177 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-28
• Study Completion Date: 2026-08-01

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).

Conditions

Macular Degeneration

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Part 1: IVT Injections

Zifibancimig administered in multiple ascending dose levels through IVT injections.

Group Type: EXPERIMENTAL

Zifibancimig

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

Zifibancimig

Intervention Type: DRUG

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.

Ranibizumab

Intervention Type: DRUG

Participants will receive ranibizumab 100 mg/mL through the PD implant

Port Delivery Platform

Intervention Type: DEVICE

Participants will receive intraocular refillable device that is surgically inserted into the eye for continuous delivery of drugs into the vitreous.

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.

Group Type: EXPERIMENTAL

Zifibancimig

Intervention Type: DRUG

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.

Ranibizumab

Intervention Type: DRUG

Participants will receive ranibizumab 100 mg/mL through the PD implant

Port Delivery Platform

Intervention Type: DEVICE

Participants will receive intraocular refillable device that is surgically inserted into the eye for continuous delivery of drugs into the vitreous.

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.

Group Type: EXPERIMENTAL

Zifibancimig

Intervention Type: DRUG

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.

Ranibizumab

Intervention Type: DRUG

Participants will receive ranibizumab 100 mg/mL through the PD implant

Port Delivery Platform

Intervention Type: DEVICE

Participants will receive intraocular refillable device that is surgically inserted into the eye for continuous delivery of drugs into the vitreous.

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.

Group Type: EXPERIMENTAL

Zifibancimig

Intervention Type: DRUG

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.

Ranibizumab

Intervention Type: DRUG

Participants will receive ranibizumab 100 mg/mL through the PD implant

Port Delivery Platform

Intervention Type: DEVICE

Participants will receive intraocular refillable device that is surgically inserted into the eye for continuous delivery of drugs into the vitreous.

Part 3: PD With Ranibizumab

100 mg/mL of ranibizumab administered through the PD implant.

Group Type: ACTIVE_COMPARATOR

Ranibizumab

Intervention Type: DRUG

Participants will receive ranibizumab 100 mg/mL through the PD implant

Interventions

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.

Intervention Type: DRUG

Ranibizumab

Participants will receive ranibizumab 100 mg/mL through the PD implant

Intervention Type: DRUG

Port Delivery Platform

Participants will receive intraocular refillable device that is surgically inserted into the eye for continuous delivery of drugs into the vitreous.

Intervention Type: DEVICE

Other Intervention Names

RO7250284

Eligibility Criteria

Inclusion Criteria

• Willing to allow AH collection

Part 1 and Part 2

• 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

• 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

Exclusion Criteria

• 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

• 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)

• 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

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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

Macula Retina Vitreous Research Institute

Torrance, California, United States

Southwest Retina Consultants

Durango, Colorado, United States

Retina Specialty Institute

Pensacola, Florida, United States

Retina Vitreous Assoc of FL

St. Petersburg, Florida, United States

Southern Vitreoretinal Assoc

Tallahassee, Florida, United States

Retina Associates of Florida, LLC

Tampa, Florida, United States

Southeast Retina Center

Augusta, Georgia, United States

University Retina and Macula Associates, PC

Oak Forest, Illinois, United States

Maine Eye Center

Portland, Maine, United States

The Retina Care Center

Baltimore, Maryland, 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.

Saint Louis Park, Minnesota, United States

Midwest Vision Research Foundation

Chesterfield, Missouri, United States

The Retina Institute

St Louis, Missouri, United States

Sierra Eye Associates

Reno, Nevada, United States

Envision Ocular, LLC

Bloomfield, New Jersey, United States

NJ Retina - Teaneck

Teaneck, New Jersey, United States

Retina Vit Surgeons/Central NY

Liverpool, New York, United States

Long Is. Vitreoretinal Consult

Westbury, New York, United States

Duke Eye Center

Durham, North Carolina, 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

Carolina Eyecare Physicians

Mt. Pleasant, 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

Bellaire, Texas, United States

Texas Retina Associates

Dallas, 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

Retina Associates of Utah, PLLC

Salt Lake City, Utah, 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

Countries

United States; Puerto Rico

Other Identifiers

BP41670

Identifier Type: -

Identifier Source: org_study_id