Clinical trial NCT05224102: A Study to Investigate Faricimab Treatment Response in Treatment-Naive, Underrepresented Patients With Diabetic Macular Edema
Official title: A Phase IV, Multicenter, Open-Label, Single-Arm Study to Investigate Faricimab (RO6867461) Treatment Response in Treatment-Naive, Underrepresented Patients With Diabetic Macular Edema
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Diabetic Macular Edema
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2022-02-04
Enrollment: 218
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: This is a multicenter, open-label, single-arm study with two phases: the main study phase for all eligible patients (up to 56 weeks), followed by an optional long-term extension phase for eligible patients only in the U.S. (up to 100 weeks).
Primary purpose: TREATMENT

Brief summary: This study is designed to investigate treatment response in treatment-naïve underrepresented patients with diabetic macular edema (DME) who are treated with faricimab. The study population will consist of participants ≥18 years of age who self-identify as Black/African American, Hispanic/Latino American, or Native American/Alaska Native/Native Hawaiian or other Pacific Islander; in addition, a cohort of Asian Indian participants will be enrolled in India.


Eligibility criteria: Inclusion Criteria:

Main Phase General Inclusion Criteria:

* Self-identify as Black/African American, Hispanic/Latino American, or Native American/Alaska Native/Native Hawaiian or other Pacific Islander; or self-identify as Asian Indian residents of the Indian subcontinent
* Diagnosis of diabetes mellitus (type 1 or type 2), as defined by the World Health Organization (WHO) and/or American Diabetes Association, and current regular use of insulin or other injectable drugs (e.g., dulaglutide and liraglutide) and/or oral anti-hyperglycemic agents for the treatment of diabetes
* Hemoglobin A1c (HbA1c) ≤10% (Note: up to 20% of participants enrolled may have HbA1c up to 12%)
* For women of childbearing potential: Agreement to remain abstinent (refrain from heterosexual intercourse) or use acceptable contraception methods as defined in the protocol

Main Phase Ocular Inclusion Criteria for Study Eye:

* Intravitreal (IVT) treatment-naïve in the study eye (i.e., have not received previous treatment with any anti-VEGF IVT or any corticosteroids periocular or IVT in the study eye)
* Diabetic macular edema, defined as macular thickening by SD-OCT involving the center of the macula
* BCVA letter score of 73 to 20 letters (both inclusive) using the ETDRS protocol at the initial testing distance of 4 meters at the baseline visit (Day 1)
* Clear ocular media and adequate pupillary dilation to allow acquisition of good quality retinal images to confirm diagnosis

Long-Term Extension (LTE) Inclusion Criteria:

* Enrollment in and completion of the main study, without discontinuation from study or study drug treatment
* Signed LTE-phase Informed Consent Form
* Ability to comply with the study protocol, in the investigator's judgment
* For women of childbearing potential: Agreement to remain abstinent (refrain from heterosexual intercourse) or use acceptable contraception methods as defined in the protocol

Exclusion Criteria:

Main Phase General Exclusion Criteria:

* Diabetes mellitus (type 1 or type 2) that is currently medically untreated
* Previously untreated diabetes mellitus (type 1 or type 2) who started on oral or injectable anti-diabetic medication within 3 months prior to Day 1
* Any known hypersensitivity to any of the components in the faricimab injection
* Any known hypersensitivity to any contrast media (e.g., fluorescein), dilating eye drops, disinfectants (e.g., iodine), or any of the anesthetics and antimicrobial preparations used by the patient during the study
* History of other diseases, other non-diabetic metabolic dysfunction, physical examination finding, or historical or current clinical laboratory finding giving reasonable suspicion of a condition that contraindicates the use of the faricimab or that might affect interpretation of the results of the study or renders the patient at high-risk for treatment complications, in the opinion of the investigator
* Active cancer within the past 12 months prior to Day 1 except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, and prostate cancer with a Gleason score of ≤6 and a stable prostate-specific antigen for \>12 months
* Stroke (cerebral vascular accident) or myocardial infarction within 12 months prior to Day 1
* Any febrile illness within 1 week prior to Day 1
* Pregnant or breastfeeding, or intending to become pregnant during the study or within 3 months after the final dose of faricimab
* Uncontrolled blood pressure, defined as systolic \>180 mmHg and/or diastolic \>100 mmHg (while patient is at rest in a sitting position); if a patient's initial reading exceeds these values, a second reading may be taken ≥30 minutes later on the same day
* Renal failure requiring renal transplant, hemodialysis, or peritoneal dialysis within 6 months prior to Day 1 or anticipated to require hemodialysis or peritoneal dialysis at any time during the study
* Any condition resulting in a compromised immune system that is likely to impact the aqueous humor inflammatory biomarkers
* Participation in an investigational trial that involves treatment with any drug or device (with the exception of vitamins or minerals) within 3 months (or 5 half-lives, whichever is longer) prior to Day 1, or during the course of this study
* Substance abuse occurring within 12 months prior to screening, in the investigator's judgment
* Use of systemic immunomodulatory treatments (e.g., IL-6 inhibitors) within 6 months or 5 half-lives (whichever is longer) prior to Day 1
* Use of any systemic corticosteroids within 1 month prior to Day 1
* Systemic treatment for suspected or active systemic infection
* Any prior or concomitant systemic anti-VEGF treatment within 6 months or 5 half-lives (whichever is longer) prior to Day 1
* Use of systemic medications known to be toxic to the lens, retina, or optic nerve (e.g., deferoxamine, chloroquine/hydroxychloroquine, tamoxifen, phenothiazines, or ethambutol) during the 6-months (or 5 half-lives, whichever is longer) prior to Day 1
* Receiving any treatment that leads to immunosuppression within 6 months (or 5 half-lives, whichever is longer) prior to Day 1
* Requiring continuous use of any medications or treatments listed as prohibited therapy

Main Phase Ocular Exclusion Criteria for Study Eye:

* High-risk proliferative diabetic retinopathy (PDR) in the study eye, using any of the following established criteria for high-risk PDR: Any vitreous or pre-retinal hemorrhage; Neovascularization elsewhere ≥1/2 disc area within an area equivalent to the mydriatic ETDRS 7 or 4 fields on clinical examination or on CFPs; Neovascularization at disc ≥1/3 disc area on clinical examination
* Tractional retinal detachment, pre-retinal fibrosis, vitreomacular traction, or epiretinal membrane involving the fovea or disrupting the macular architecture in the study eye, as evaluated by the central reading center
* Any history of or ongoing rubeosis iridis
* Any panretinal photocoagulation or macular laser (focal, grid or micropulse) photocoagulation treatment received in the study eye prior Day 1
* Any history of treatment with anti-VEGF or any periocular or IVT corticosteroids in the study eye prior to Day 1
* Any treatment for dry eye disease in the last month prior to Day 1 (e.g., cyclosporine eye drops, lifitegrast eye drops). Lubricating eye drops and ointments are permitted.
* Any treatment with anti-inflammatory eye drops (e.g., doxycycline) within 1 month prior to Day 1
* Any intraocular surgery (e.g., cataract surgery) within 3 months prior to Day 1 or any planned surgery during the study
* Any glaucoma surgery prior to the screening visit
* History of vitreoretinal surgery/pars plana vitrectomy, corneal transplant, or radiotherapy
* Uncontrolled glaucoma
* Any active or suspected ocular or periocular infections on Day 1
* Any presence of active intraocular inflammation on Day 1 (i.e., Standardization of Uveitis Nomenclature \[SUN\] criteria \>0 or National Eye Institute \[NEI\] vitreous haze grading \>0) or any history of intraocular inflammation
* Any history of idiopathic, infectious, or noninfectious uveitis
* Any current ocular condition or other causes of visual impairment for which, in the opinion of the investigator, visual acuity loss would not improve from resolution of macular edema

Main Phase Ocular Exclusion Criteria for Non-Study Eye:

* Any history of idiopathic or immune-mediated uveitis
* Active ocular inflammation or suspected or active ocular or periocular infection on Day 1
* Currently receiving treatment with brolucizumab or bevacizumab in the non-study eye and is unwilling to switch to a protocol-allowed, non-study eye anti-VEGF treatment during the study
* Any previous treatment with Iluvien® or Retisert® (fluocinolone acetonide IVT implant) in the non-study eye
* Non-functioning non-study eye, defined as either: BCVA of hand motion or worse; No physical presence of non-study eye (i.e., monocular); or, Legally blind in the patient's relevant jurisdiction

Long-Term Extension (LTE) Exclusion Criteria:

* Pregnant or breastfeeding, or intending to become pregnant during the study or within 3 months after the final IVT injection of faricimab
* Presence of other ocular diseases that give reasonable suspicion of a disease or condition that contraindicates the use of faricimab, that might affect interpretation of the results of the LTE, or that renders the patient at high risk for treatment complications
* Presence of other diseases, metabolic dysfunction, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of faricimab and that might affect interpretation of the results of the LTE, or that renders the patient at high risk of treatment complications
* History of a severe allergic reaction or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of the faricimab injections, study treatment procedure, dilating drops, or any of the anesthetic and antimicrobial preparations used by a patient during the LTE phase
* Requirement for continuous use of any medications or treatments indicated as prohibited therapy (as defined in the protocol)

Primary outcomes:
measure: Main Phase: Change in Best Corrected Visual Acuity (BCVA) from Baseline at Week 56, as Measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) Chart at a Starting Distance of 4 Meters
timeFrame: From Baseline to Week 56
measure: Long-Term Extension Phase: Incidence and Severity of Ocular Adverse Events
timeFrame: From Day 1 until end of long-term extension (up to 100 weeks)
measure: Long-Term Extension Phase: Incidence and Severity of Non-Ocular Adverse Events
timeFrame: From Day 1 until end of long-term extension (up to 100 weeks)
Secondary outcomes:
measure: Main Phase: Percentage of Participants with a Greater Than or Equal to (≥)2-Step ETDRS Diabetic Retinopathy Severity Scale (DRSS) Improvement from Baseline Over Time
timeFrame: Baseline and Weeks 20 and 56
measure: Main Phase: Percentage of Participants with a ≥3-Step ETDRS Diabetic Retinopathy Severity Scale (DRSS) Improvement from Baseline Over Time
timeFrame: Baseline and Weeks 20 and 56
measure: Main Phase: Percentage of Participants with Absence of Intraretinal Fluid Over Time
timeFrame: Baseline and Weeks 4, 8, 12, 16, 20, 28, 36, 44, 48, 52, and 56
measure: Main Phase: Percentage of Participants with Absence of Subretinal Fluid Over Time
timeFrame: Baseline and Weeks 4, 8, 12, 16, 20, 28, 36, 44, 48, 52, and 56
measure: Main Phase: Change from Baseline in Central Subfield Thickness Over Time
timeFrame: Baseline and Weeks 4, 8, 12, 16, 20, 28, 36, 44, 48, 52, and 56
measure: Main Phase: Percentage of Participants Gaining ≥15 or ≥10 Letters in BCVA from Baseline at Week 56
timeFrame: Baseline and Week 56
measure: Main Phase: Percentage of Participants Avoiding a Loss of ≥15 or ≥10 Letters in BCVA from Baseline at Week 56
timeFrame: Baseline and Week 56
measure: Main Phase: Incidence and Severity of Ocular Adverse Events
timeFrame: From Baseline up to Week 56
measure: Main Phase: Incidence and Severity of Non-Ocular Adverse Events
timeFrame: From Baseline up to Week 56
measure: Main Phase: Number of Participants Testing Positive for Anti-Drug Antibodies (ADAs) Against Faricimab at Baseline and Anytime During the Study
timeFrame: From Baseline up to Week 56
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Barnet Dulaney Perkins Eye Center
state: Arizona
city: Arcadia
country: United States
facility: Win Retina
state: California
city: Campbell
country: United States
facility: Retinal Diagnostic Center
state: California
city: Fullerton
country: United States
facility: Retina Consultants of Orange County
state: California
city: Los Angeles
country: United States
facility: Kaiser Permanente Southern California
state: California
city: Sacramento
country: United States
facility: Retinal Consultants Medical Group
state: California
city: Durango
country: United States
facility: Southwest Retina Consultants
state: Colorado
city: Washington
country: United States
facility: Emerson Clinical Research Institute LLC
state: District of Columbia
city: Clearwater
country: United States
facility: Blue Ocean Clinical Research
state: Florida
city: Miami
country: United States
facility: Retina Macula Specialists of Miami - LeJeune Road Office
state: Florida
city: Orlando
country: United States
facility: Florida Retina Institute
state: Florida
city: Plantation
country: United States
facility: Fort Lauderdale Eye Institute
state: Florida
city: Oak Forest
country: United States
facility: University Retina and Macula Associates, PC
state: Illinois
city: Baltimore
country: United States
facility: Wilmer Eye Institute Johns Hopkins University
state: Maryland
city: Oxon Hill
country: United States
facility: Md Medical Research
state: Maryland
city: Grand Blanc
country: United States
facility: Retina Associates of Michigan
state: Michigan
city: Henderson
country: United States
facility: Retina Consultants of Nevada
state: Nevada
city: Reno
country: United States
facility: Sierra Eye Associates
state: Nevada
city: Bloomfield
country: United States
facility: The Retina Center of New Jersey
state: New Jersey
city: Teaneck
country: United States
facility: NJ Retina - Teaneck
state: New Jersey
city: Winston-Salem
country: United States
facility: Piedmont Retina Specialists
state: North Carolina
city: Beachwood
country: United States
facility: Retina Associates of Cleveland, INC
state: Ohio
city: Philadelphia
country: United States
facility: Scheie Eye Institute
state: Pennsylvania
city: Philadelphia
country: United States
facility: Wills Eye Hospital
state: Pennsylvania
city: Rapid City
country: United States
facility: Black Hills Eye Institute
state: South Dakota
city: Memphis
country: United States
facility: Charles Retina Institute
state: Tennessee
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: San Antonio
country: United States
facility: Brown Retina Institute
state: Texas
city: Southlake
country: United States
facility: Retina Center of Texas
state: Texas
city: Willow Park
country: United States
facility: Strategic Clinical Research Group, LLC
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: Hubli
country: India
facility: MM Joshi Eye Institute
state: Karnataka
city: Pune City
country: India
facility: PBMA'S H. V. Desai Eye Hospital
state: Maharashtra
city: Ahmedabad
country: India
facility: M & J Western Regional Institute of Ophthalmology
state: Rajasthan
city: Chennai
country: India
facility: Sankara Nethralaya
state: Tamil NADU
city: Madurai
country: India
facility: Aravind Eye Hospital
state: Tamil NADU
city: Kolkata
country: India
facility: Regional Institute of Ophthalmology
state: WEST Bengal
city: Chandigarh
country: India
facility: Post Graduate Institute of Medical Education and Research (PGIMER)
city: Nairobi
country: Kenya
facility: Nairobi Hospital
city: Nairobi
country: Kenya
facility: City Eye Hospital
city: Arecibo
country: Puerto Rico
facility: Emanuelli Research and Development Center LLC
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
References: