Clinical trial NCT04567303: Study of Zifibancimig in Participants With Neovascular Age-Related Macular Degeneration
Official title: A Three-Part, Phase I/II 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Macular Degeneration
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2020-09-28
Enrollment: 251
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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)


Eligibility 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 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 during the last 3 months prior to screening.
* 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 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).

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 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

Primary outcomes:
measure: Percentage of Participants with Ocular and Systemic (Nonocular) Adverse Events (AEs)
timeFrame: Part 1: Baseline up to Week 24; Part 2: Baseline up to Week 48; Part 3: Baseline up to Week 48
measure: Percentage of Participants with Ocular and Systemic (Nonocular) AEs during Post-operative and Follow-up Periods
timeFrame: Part 2 and 3: From Day 1 to Week 4 and during follow up period (up to Week 48)
measure: Percentage of Participants with Adverse Events of Special Interest (AESIs) including Ocular AESIs
timeFrame: Part 1: Baseline up to Week 24; Part 2: Baseline up to Week 48; Part 3: Baseline up to Week 48
measure: Percentage of Participants with AESIs including Ocular AESIs during the Postoperative and Follow-up periods
timeFrame: Part 2 and 3: From Day 1 to Week 4 and during follow up period (up to Week 48)
measure: Duration of AESIs including Ocular AESIs
timeFrame: Part 1: Baseline up to Week 24; Part 2: Baseline up to Week 48; Part 3: Baseline up to Week 48
measure: Duration of AESIs including Ocular AESIs during the Postoperative and Follow-up periods
timeFrame: Part 2 and 3: From Day 1 to Week 4 and during follow up period (up to Week 48)
measure: Percentage of Participants with Adverse Device Effects (ADEs)
timeFrame: Part 2: Baseline up to Week 48; Part 3: Baseline up to Week 48
measure: Duration of ADEs
timeFrame: Part 2: Baseline up to Week 48; Part 3: Baseline up to Week 48
measure: Percentage of Participants with Anticipated Serious ADEs (ASADEs)
timeFrame: Part 2: Baseline up to Week 48; Part 3: Baseline up to Week 48
measure: Duration of ASADEs
timeFrame: Part 2: Baseline up to Week 48; Part 3: Baseline up to Week 48
measure: Change from Baseline in Early Treatment Diabetic Retinopathy Study - Best Corrected Visual Acuity (ETDRS-BCVA) Score
timeFrame: Part 3: Baseline (baseline visit, before implant insertion) to Week 48
Secondary outcomes:
measure: Maximum Observed Concentration (Cmax) of Zifibancimig in Blood and Aqueous Humor (AH)
timeFrame: Part 1: Baseline up to Week 24; Part 2: Baseline up to Week 144; Part 3: Baseline up to Week 144
measure: Time of Maximum Concentration Observed (Tmax) of Zifibancimig in Blood and AH
timeFrame: Part 1: Baseline up to Week 24; Part 2: Baseline up to Week 144; Part 3: Baseline up to Week 144
measure: Concentration at the End of a Dosing Interval before the Next Dose Administration (Ctrough) of Zifibancimig in Blood and AH
timeFrame: Part 1: Baseline up to Week 24; Part 2: Baseline up to Week 144; Part 3: Baseline up to Week 144
measure: Area Under the Curve (AUC) of Zifibancimig in Blood and AH
timeFrame: Part 1: Baseline up to Week 24; Part 2: Baseline up to Week 144; Part 3: Baseline up to Week 144
measure: Percentage of Participants who did not meet Supplemental Treatment Criteria for the PD implant with Zifibancimig
timeFrame: Part 3: Week 36, Week 40, and Week 44
measure: Percentage of Participants who Gained or Lost ≥15, ≥10 ≥5 or ≥0 letters in ETDRS-BCVA score from Baseline
timeFrame: Part 3: Baseline to Week 48
measure: Change from Baseline in Central Subfield Thickness (CST)
timeFrame: Part 3: Baseline to Week 48
measure: Change from Baseline Over Time in CST
timeFrame: Part 3: Baseline to end of follow up period (up to Week 144)
Other outcomes:
Locations:
city: Mesa
country: United States
facility: Barnet Dulaney Perkins Eye Center
state: Arizona
city: Phoenix
country: United States
facility: Associated Retina Consultants
state: Arizona
city: Encino
country: United States
facility: The Retina Partners
state: California
city: Sacramento
country: United States
facility: Retinal Consultants Med Group
state: California
city: San Francisco
country: United States
facility: West Coast Retina Medical Group
state: California
city: Santa Ana
country: United States
facility: Orange County Retina Med Group
state: California
city: Durango
country: United States
facility: Southwest Retina Consultants
state: Colorado
city: Pensacola
country: United States
facility: Retina Specialty Institute
state: Florida
city: Saint Petersburg
country: United States
facility: Retina Vitreous Assoc of FL
state: Florida
city: Tallahassee
country: United States
facility: Southern Vitreoretinal Assoc
state: Florida
city: Tampa
country: United States
facility: Retina Associates of Florida, LLC
state: Florida
city: Augusta
country: United States
facility: Southeast Retina Center
state: Georgia
city: Oak Forest
country: United States
facility: University Retina and Macula Associates, PC
state: Illinois
city: Portland
country: United States
facility: Maine Eye Center
state: Maine
city: Baltimore
country: United States
facility: The Retina Care Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Med
state: Maryland
city: Chevy Chase
country: United States
facility: Retina Group of Washington
state: Maryland
city: Hagerstown
country: United States
facility: Cumberland Valley Retina Consultants
state: Maryland
city: Grand Rapids
country: United States
facility: Foundation for Vision Research
state: Michigan
city: Royal Oak
country: United States
facility: Associated Retinal Consultants
state: Michigan
city: Edina
country: United States
facility: VitreoRetinal Surgery, PLLC.
state: Minnesota
city: Chesterfield
country: United States
facility: Midwest Vision Research Foundation
state: Missouri
city: Saint Louis
country: United States
facility: The Retina Institute
state: Missouri
city: Reno
country: United States
facility: Sierra Eye Associates
state: Nevada
city: Bloomfield
country: United States
facility: Envision Ocular, LLC
state: New Jersey
city: Hauppauge
country: United States
facility: Long Is. Vitreoretinal Consult
state: New York
city: Liverpool
country: United States
facility: Retina Vit Surgeons/Central NY
state: New York
city: Hickory
country: United States
facility: Graystone Eye
state: North Carolina
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: OSU Eye Physicians & Surgeons
state: Ohio
city: Philadelphia
country: United States
facility: Mid Atlantic Retina - Wills Eye Hospital
state: Pennsylvania
city: Ladson
country: United States
facility: Charleston Neuroscience Inst
state: South Carolina
city: Germantown
country: United States
facility: Charles Retina Institute
state: Tennessee
city: Knoxville
country: United States
facility: Southeastern Retina Associates
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Retina PC.
state: Tennessee
city: Abilene
country: United States
facility: Retina Res Institute of Texas
state: Texas
city: Austin
country: United States
facility: Austin Research Center for Retina
state: Texas
city: Austin
country: United States
facility: Austin Clinical Research LLC
state: Texas
city: Bellaire
country: United States
facility: Retina & Vitreous of Texas
state: Texas
city: Bellaire
country: United States
facility: Retina Consultants of Texas
state: Texas
city: Dallas
country: United States
facility: Texas Retina Associates
state: Texas
city: Houston
country: United States
facility: Retina Consultants of Texas
state: Texas
city: San Antonio
country: United States
facility: Brown Retina Institute
state: Texas
city: Southlake
country: United States
facility: Retina Center of Texas
state: Texas
city: Lynchburg
country: United States
facility: Piedmont Eye Center
state: Virginia
city: Norfolk
country: United States
facility: Wagner Kapoor Institute
state: Virginia
city: Spokane
country: United States
facility: Spokane Eye Clinical Research
state: Washington
city: Arecibo
country: Puerto Rico
facility: Emanuelli Research and Development Center LLC
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: