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

Macular Degeneration Clinical Trial

— BURGUNDY  

Official title:

A Three-Part, Phase I 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04567303
• Other study ID #: BP41670
• Status: Recruiting
• Phase: Phase 1
• Start date: October 28, 2020
• Est. completion date: December 29, 2027

Study information

• Verified date: June 2024
• Source: Hoffmann-La Roche
• Contact: BP41670 https://forpatients.roche.com/
• Phone: 888-662-6728 (U.S. Only)
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 251
• Est. completion date: December 29, 2027
• Est. primary completion date: February 9, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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 nine months prior to the screening visit.

• Previous treatment with at least two 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 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.

• 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 anti-VEGF or anti-VEGF/Ang-2 agents within one month prior to Day 1 (for Part 1) or prior to the randomization visit (Part 3).

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.

• Active intraocular inflammation (grade trace or above), infectious conjunctivitis, keratitis, scleritis, or endophthalmitis.

• History of uveitis, including history of any intraocular inflammation following intravitreal anti-VEGFor anti-VEGF/Ang-2 injections.

• Prior treatment with brolucizumab.

• Prior gene therapy for nAMD

Related Conditions & MeSH terms

• Macular Degeneration

Intervention

Drug:
• Zifibancimig
Part 1: multiple ascending doses by IVT injection. Each participant will receive zifibancimig at a constant volume of 50 microliter 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
Participants will receive ranibizumab 100 mg/mL 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.

Locations

Country	Name	City	State
United States	Southeast Retina Center	Augusta	Georgia
United States	Austin Clinical Research LLC	Austin	Texas
United States	Austin Research Center for Retina	Austin	Texas
United States	Retina & Vitreous of Texas	Bellaire	Texas
United States	Envision Ocular, LLC	Bloomfield	New Jersey
United States	Midwest Vision Research Foundation	Chesterfield	Missouri
United States	Southwest Retina Consultants	Durango	Colorado
United States	Cumberland Valley Retina Associates	Hagerstown	Maryland
United States	Southeastern Retina Associates	Knoxville	Tennessee
United States	Piedmont Eye Center	Lynchburg	Virginia
United States	Barnet Dulaney Perkins Eye Center	Mesa	Arizona
United States	Tennessee Retina PC.	Nashville	Tennessee
United States	Mid Atlantic Retina - Wills Eye Hospital	Philadelphia	Pennsylvania
United States	Associated Retina Consultants	Phoenix	Arizona
United States	Sierra Eye Associates	Reno	Nevada
United States	Retina Vitreous Assoc of FL	Saint Petersburg	Florida
United States	Spokane Eye Clinical Research	Spokane	Washington
United States	Southern Vitreoretinal Assoc	Tallahassee	Florida
United States	Retina Associates of Florida, LLC	Tampa	Florida
United States	Retina Consultants of Texas	The Woodlands	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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)
Primary	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
Primary	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)
Primary	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
Primary	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)
Primary	Percentage of Participants with Adverse Device Effects (ADEs)		Part 2: Baseline up to Week 48; Part 3: Baseline up to Week 48
Primary	Duration of ADEs		Part 2: Baseline up to Week 48; Part 3: Baseline up to Week 48
Primary	Percentage of Participants with Anticipated Serious ADEs (ASADEs)		Part 2: Baseline up to Week 48; Part 3: Baseline up to Week 48
Primary	Duration of ASADEs		Part 2: Baseline up to Week 48; Part 3: Baseline up to Week 48
Primary	Change from Baseline in Early Treatment Diabetic Retinopathy Study - Best Corrected Visual Acuity (ETDRS-BCVA) Score	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) to Week 48
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Percentage of Participants who Gained or Lost =15, =10 =5 or =0 letters in ETDRS-BCVA score from Baseline	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
Secondary	Change from Baseline in Central Subfield Thickness (CST)		Part 3: Baseline to Week 48
Secondary	Change from Baseline Over Time in CST		Part 3: Baseline to end of follow up period (up to Week 144)