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

NCT04567303 | Active Not Recruiting Phase 1 FDA Drug FDA Device

• 1 other identifier: BP41670
• Study Type: interventional
• Target: 177
• Locations: 2 countries
• Sites: 48

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

Outcome Measures

Primary Outcomes (11)

• 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 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

• 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

  Part 1: Baseline up to Week 24; Parts 2 and 3: Baseline 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)

• 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

• 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 Outcomes (8)

• 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 did not Meet Supplemental Treatment Criteria for the PD Implant With Zifibancimig

  Part 3: Week 36, Week 40, and Week 44

Study Arms (6)

Part 1: IVT Injections

EXPERIMENTAL

Zifibancimig administered in multiple ascending dose levels through IVT injections.

Drug: Zifibancimig

Part 2: PD With High Dose

EXPERIMENTAL

Zifibancimig administered at a high dose through the PD implant, followed by ranibizumab, 100 milligrams per milliliter (mg/mL), administered through the PD implant.

Drug: Zifibancimig; Drug: Ranibizumab; Device: Port Delivery Platform

Part 2: PD With Low Dose

EXPERIMENTAL

Zifibancimig administered at a low dose through the PD implant, followed by ranibizumab, 100 mg/mL, administered through the PD implant.

Drug: Zifibancimig; Drug: Ranibizumab; Device: Port Delivery Platform

Part 3: PD With High Dose

EXPERIMENTAL

Zifibancimig administered at a high dose through the PD implant, followed by ranibizumab, 100 mg/mL, administered through PD implant.

Drug: Zifibancimig; Drug: Ranibizumab; Device: Port Delivery Platform

Part 3: PD With Low Dose

EXPERIMENTAL

Zifibancimig administered at a low dose through the PD implant, followed by ranibizumab, 100 mg/mL, administered through PD implant.

Drug: Zifibancimig; Drug: Ranibizumab; Device: Port Delivery Platform

Part 3: PD With Ranibizumab

ACTIVE COMPARATOR

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

Drug: Ranibizumab

Interventions

Zifibancimig 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.

Also known as: RO7250284

Part 1: IVT Injections; Part 2: PD With High Dose; Part 2: PD With Low Dose; Part 3: PD With High Dose; Part 3: PD With Low Dose

Ranibizumab DRUG

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

Part 2: PD With High Dose; Part 2: PD With Low Dose; Part 3: PD With High Dose; Part 3: PD With Low Dose; Part 3: PD With Ranibizumab

Port Delivery Platform 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 High Dose; Part 2: PD With Low Dose; Part 3: PD With High Dose; Part 3: PD With Low Dose

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (48)

Barnet Dulaney Perkins Eye Center

Mesa, Arizona, 85206, United States

Location

Associated Retina Consultants

Phoenix, Arizona, 85020, United States

Location

The Retina Partners

Encino, California, 91436, United States

Location

Retinal Consultants Med Group

Sacramento, California, 95841, United States

Location

Orange County Retina Med Group

Santa Ana, California, 92705, United States

Location

Macula Retina Vitreous Research Institute

Torrance, California, 90503-3270, United States

Location

Southwest Retina Consultants

Durango, Colorado, 81303, United States

Location

Retina Specialty Institute

Pensacola, Florida, 32503, United States

Location

Retina Vitreous Assoc of FL

St. Petersburg, Florida, 33711, United States

Location

Southern Vitreoretinal Assoc

Tallahassee, Florida, 32308, United States

Location

Retina Associates of Florida, LLC

Tampa, Florida, 33609, United States

Location

Southeast Retina Center

Augusta, Georgia, 30909, United States

Location

University Retina and Macula Associates, PC

Oak Forest, Illinois, 60452, United States

Location

Maine Eye Center

Portland, Maine, 04101, United States

Location

The Retina Care Center

Baltimore, Maryland, 21209, United States

Location

Johns Hopkins Med

Baltimore, Maryland, 21287, United States

Location

Retina Group of Washington

Chevy Chase, Maryland, 20815, United States

Location

Cumberland Valley Retina Consultants

Hagerstown, Maryland, 21740, United States

Location

Foundation for Vision Research

Grand Rapids, Michigan, 49546, United States

Location

Associated Retinal Consultants

Royal Oak, Michigan, 48073, United States

Location

VitreoRetinal Surgery, PLLC.

Saint Louis Park, Minnesota, 55416, United States

Location

Midwest Vision Research Foundation

Chesterfield, Missouri, 63017, United States

Location

The Retina Institute

St Louis, Missouri, 63128, United States

Location

Sierra Eye Associates

Reno, Nevada, 89502, United States

Location

Envision Ocular, LLC

Bloomfield, New Jersey, 07003, United States

Location

NJ Retina - Teaneck

Teaneck, New Jersey, 07666-1704, United States

Location

Retina Vit Surgeons/Central NY

Liverpool, New York, 13088, United States

Location

Long Is. Vitreoretinal Consult

Westbury, New York, 11590, United States

Location

Duke Eye Center

Durham, North Carolina, 27705, United States

Location

Graystone Eye

Hickory, North Carolina, 28602, United States

Location

OSU Eye Physicians & Surgeons

Columbus, Ohio, 43212, United States

Location

Mid Atlantic Retina - Wills Eye Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Charleston Neuroscience Inst

Ladson, South Carolina, 39456, United States

Location

Carolina Eyecare Physicians

Mt. Pleasant, South Carolina, 29464, United States

Location

Charles Retina Institute

Germantown, Tennessee, 38138, United States

Location

Southeastern Retina Associates

Knoxville, Tennessee, 37922, United States

Location

Tennessee Retina PC.

Nashville, Tennessee, 37203, United States

Location

Austin Research Center for Retina

Austin, Texas, 78705, United States

Location

Austin Clinical Research LLC

Austin, Texas, 78750, United States

Location

Retina Consultants of Texas

Bellaire, Texas, 77401, United States

Location

Texas Retina Associates

Dallas, Texas, 75231, United States

Location

Retina Consultants of Texas

Houston, Texas, 77030, United States

Location

Brown Retina Institute

San Antonio, Texas, 78251-4551, United States

Location

Retina Center of Texas

Southlake, Texas, 76092, United States

Location

Piedmont Eye Center

Lynchburg, Virginia, 24502, United States

Location

Wagner Kapoor Institute

Norfolk, Virginia, 23502, United States

Location

Spokane Eye Clinical Research

Spokane, Washington, 99204, United States

Location

Emanuelli Research and Development Center LLC

Arecibo, 00612, Puerto Rico

Location

MeSH Terms

Conditions

Macular Degeneration

Interventions

Ranibizumab

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Part 1: Visual Acuity (VA) examiner; Part 2: Participant, Investigator, VA examiner and Sponsor; Part 3: Participant, Investigator, VA examiner and Sponsor. The sponsor and its agents have been unblinded to treatment assignment in Parts 2 and 3, as of protocol amendment version 12.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part 1 of the study will be an open-label multiple ascending dose (MAD) study, followed by subsequent assignment to 2 groups in Part 2. Part 3 will enroll new participants to compare the efficacy of zifibancimig PD implant versus ranibizumab released via the PD implant.

Study Record Dates

• First Submitted: September 24, 2020
• First Posted: September 28, 2020
• Study Start: October 28, 2020
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: February 4, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

US (47); PR (1)