Macular Degeneration
Conditions
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).
Interventions
DRUGZifibancimig
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.
DRUGRanibizumab
Participants will receive ranibizumab 100 mg/mL through the PD implant
DEVICEPort Delivery Platform
Participants will receive intraocular refillable device that is surgically inserted into the eye for continuous delivery of drugs into the vitreous.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, 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. The sponsor and its agents have been unblinded to treatment assignment in Parts 2 and 3, as of protocol amendment version 12.
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion 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 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Part 3: Baseline (baseline visit, before implant insertion), and 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| Percentage of Participants Who Gained or Lost ≥15, ≥10 ≥5 or ≥0 Letters in ETDRS-BCVA Score From Baseline to Week 48 | 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. |
| 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) | — |
Countries
Puerto Rico, United States
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Outcome results
None listed