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

• ClinicalTrials.gov Identifier: NCT04567303
• Recruitment Status: Recruiting
• First Posted: September 28, 2020
• Last Update Posted: August 23, 2023
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

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)

Condition or disease	Intervention/treatment	Phase
Macular Degeneration	Drug: Zifibancimig; Drug: Ranibizumab; Device: Port Delivery Platform	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 251 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Part 1 of the study will be an open-label multiple ascending dose 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.
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Masking Description: Part 1: Visual Acuity (VA) examiner; Part 2: Participant, Investigator, VA examiner and Sponsor; Part 3: Participant, Investigator, VA examiner and Sponsor
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: October 28, 2020
• Estimated Primary Completion Date: May 31, 2025
• Estimated Study Completion Date: March 31, 2027

Arms and Interventions

Arm	Intervention/treatment
Experimental: Part 1: Intravitreal Injections; Zifibancimig administered in 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 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 Name: RO7250284
Experimental: Part 2: Port Delivery with High Dose; Zifibancimig administered at a high dose 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 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 Name: RO7250284; 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.
Experimental: Part 2: Port Delivery with Low Dose; Zifibancimig administered at a low dose 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 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 Name: RO7250284; 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.
Experimental: Part 3: Port Delivery with High Dose; Zifibancimig administered at a high dose 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 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 Name: RO7250284; 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.
Experimental: Part 3: Port Delivery with Low Dose; Zifibancimig administered at a low dose 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 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 Name: RO7250284; 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.
Active Comparator: Part 3: Port Delivery with Ranibizumab; 100 milligrams/milliliter (mg/mL) of ranibizumab administered through the PD implant.	Drug: 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.

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants with Ocular and Systemic (Nonocular) Adverse Events (AEs) [ Time Frame: Part 1: Baseline up to Week 24; Part 2: Baseline up to Week 48; Part 3: Baseline up to Week 48 ]
2. Percentage of Participants with Ocular and Systemic (Nonocular) AEs during Post-operative and Follow-up Periods [ Time Frame: Part 2 and 3: From Day 1 to Week 4 and during follow up period (up to Week 48) ]
3. Percentage of Participants with Adverse Events of Special Interest (AESIs) including Ocular AESIs [ Time Frame: Part 1: Baseline up to Week 24; Part 2: Baseline up to Week 48; Part 3: Baseline up to Week 48 ]
4. Percentage of Participants with AESIs including Ocular AESIs during the Postoperative and Follow-up periods [ Time Frame: Part 2 and 3: From Day 1 to Week 4 and during follow up period (up to Week 48) ]
5. Duration of AESIs including Ocular AESIs [ Time Frame: Part 1: Baseline up to Week 24; Part 2: Baseline up to Week 48; Part 3: Baseline up to Week 48 ]
6. Duration of AESIs including Ocular AESIs during the Postoperative and Follow-up periods [ Time Frame: Part 2 and 3: From Day 1 to Week 4 and during follow up period (up to Week 48) ]
7. Percentage of Participants with Adverse Device Effects (ADEs) [ Time Frame: Part 2: Baseline up to Week 48; Part 3: Baseline up to Week 48 ]
8. Duration of ADEs [ Time Frame: Part 2: Baseline up to Week 48; Part 3: Baseline up to Week 48 ]
9. Percentage of Participants with Anticipated Serious ADEs (ASADEs) [ Time Frame: Part 2: Baseline up to Week 48; Part 3: Baseline up to Week 48 ]
10. Duration of ASADEs [ Time Frame: Part 2: Baseline up to Week 48; Part 3: Baseline up to Week 48 ]
11. Change from Baseline in Early Treatment Diabetic Retinopathy Study - Best Corrected Visual Acuity (ETDRS-BCVA) Score [ Time Frame: 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.

Secondary Outcome Measures :

1. Maximum Observed Concentration (Cmax) of Zifibancimig in Blood and Aqueous Humor (AH) [ Time Frame: Part 1: Baseline up to Week 24; Part 2: Baseline up to Week 144; Part 3: Baseline up to Week 144 ]
2. Time of Maximum Concentration Observed (Tmax) of Zifibancimig in Blood and AH [ Time Frame: Part 1: Baseline up to Week 24; Part 2: Baseline up to Week 144; Part 3: Baseline up to Week 144 ]
3. Concentration at the End of a Dosing Interval before the Next Dose Administration (Ctrough) of Zifibancimig in Blood and AH [ Time Frame: Part 1: Baseline up to Week 24; Part 2: Baseline up to Week 144; Part 3: Baseline up to Week 144 ]
4. Area Under the Curve (AUC) of Zifibancimig in Blood and AH [ Time Frame: Part 1: Baseline up to Week 24; Part 2: Baseline up to Week 144; Part 3: Baseline up to Week 144 ]
5. Percentage of Participants who did not meet Supplemental Treatment Criteria for the PD implant with Zifibancimig [ Time Frame: Part 3: Week 40 and Week 44 ]
6. Percentage of Participants who Gained or Lost ≥15, ≥10 ≥5 or ≥0 letters in ETDRS-BCVA score from Baseline [ Time Frame: 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.
7. Change from Baseline in Central Subfield Thickness (CST) [ Time Frame: Part 3: Baseline to Week 48 ]
8. Change from Baseline Over Time in CST [ Time Frame: Baseline to end of follow up period (up to Week 144) ]

Eligibility Criteria

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

Criteria

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 73 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.

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

Contacts and Locations

Contacts

Contact: BP41670 https://forpatients.roche.com/; 888-662-6728 (U.S. Only); global-roche-genentech-trials@gene.com

Locations

United States, Arizona

Barnet Dulaney Perkins Eye Center; Active, not recruiting

Mesa, Arizona, United States, 85206

United States, Florida

Retina Vitreous Assoc of FL; Recruiting

Saint Petersburg, Florida, United States, 33711

Southern Vitreoretinal Assoc; Recruiting

Tallahassee, Florida, United States, 32308

United States, Georgia

Southeast Retina Center; Recruiting

Augusta, Georgia, United States, 30909

United States, Nevada

Sierra Eye Associates; Active, not recruiting

Reno, Nevada, United States, 89502

United States, New Jersey

Envision Ocular, LLC; Active, not recruiting

Bloomfield, New Jersey, United States, 07003

United States, Pennsylvania

Mid Atlantic Retina - Wills Eye Hospital; Recruiting

Philadelphia, Pennsylvania, United States, 19107

United States, Tennessee

Tennessee Retina PC.; Recruiting

Nashville, Tennessee, United States, 37203

United States, Texas

Austin Research Center for Retina; Active, not recruiting

Austin, Texas, United States, 78705

Retina Consultants of Texas; Active, not recruiting

The Woodlands, Texas, United States, 77384-4167

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

More Information

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT04567303
• Other Study ID Numbers: BP41670
• First Posted: September 28, 2020
• Last Update Posted: August 23, 2023
• Last Verified: August 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes

Additional relevant MeSH terms:

Macular Degeneration; Retinal Degeneration; Retinal Diseases; Eye Diseases; Ranibizumab; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Antineoplastic Agents