Clinical trial NCT02699450: A Study of Faricimab (RO6867461) in Participants With Center-Involving Diabetic Macular Edema
Official title: A Multiple-Center, Multiple-Dose, Randomized, Active Comparator-Controlled, Double-Masked, Parallel Group, 36-Week Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Efficacy of RO6867461 Administered Intravitreally in Patients With Diabetic Macular Edema
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetic Macular Edema
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2016-03-04
Enrollment: 229
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multiple-center, multiple-dose, randomized, active comparator-controlled, double-masked, three parallel group, 36-week study in participants with center-involving diabetic macular edema (DME). Only one eye will be selected as the study eye. Where both eyes meet all eligibility criteria, the eye with the worse best corrected visual acuity (BCVA) will be defined as the study eye. The study will consist of a treatment period (20 weeks) and an observational period (up to 16 weeks). Treatment naive participants will be randomized in a 1:1:1 ratio to one of the Arms A, B and C, respectively. Participants previously treated with intravitreal (IVT) anti-vascular endothelial growth factor (VEGF) will be randomized in a 1:1 ratio to Arms A and C.


Eligibility criteria: Inclusion Criteria:

* Macular edema associated with diabetic retinopathy
* Decreased visual acuity attributable primarily to DME
* Diagnosis of diabetes mellitus

Exclusion Criteria:

* High risk proliferative diabetic retinopathy
* Cataract surgery within 3 months of Baseline, or any other previous intraocular surgery
* Uncontrolled glaucoma
* Current or history of ocular disease in the study eye other than DME
* Major illness or major surgical procedure within 1 month prior to Day 1
* Uncontrolled blood pressure
* Glycosylated hemoglobin (HbA1c) greater than (\>) 12 percent (%) at screening
* Untreated diabetes mellitus or initiation of oral anti-diabetic medication or insulin within 4 months prior to Day 1

Primary outcomes:
measure: Mean Change From Baseline in BCVA Letter Score at Week 24, in Treatment-Naive Participants
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: Mean Change From Baseline in BCVA Letter Score at Week 24, in Previously Treated Participants
timeFrame: Baseline, Week 24
measure: Mean Change From Baseline in BCVA Letter Score at Week 24, in All Participants
timeFrame: Baseline, Week 24
measure: Mean Percentage of Participants Who Gained ≥15 ETDRS Letters From Baseline BCVA Score at Week 24, in Treatment-Naive Participants
timeFrame: Baseline, Week 24
measure: Mean Percentage of Participants Who Gained ≥15 ETDRS Letters From Baseline BCVA Score at Week 24, in Previously Treated Participants
timeFrame: Baseline up to Week 24
measure: Mean Percentage of Participants Who Gained ≥15 ETDRS Letters From Baseline BCVA Score at Week 24, in All Participants
timeFrame: Baseline up to Week 24
measure: Mean Percentage of Participants With BCVA ≥69 Letters (20/40 or Better) at Week 24, in Treatment-Naive Participants
timeFrame: Week 24
measure: Mean Percentage of Participants With BCVA ≥69 Letters (20/40 or Better) at Week 24, in Previously Treated Participants
timeFrame: Week 24
measure: Mean Percentage of Participants With BCVA ≥69 Letters (20/40 or Better) at Week 24, in All Participants
timeFrame: Week 24
measure: Mean Percentage of Participants With BCVA ≥84 Letters (20/20 or Better) at Week 24, in Treatment-Naive Participants
timeFrame: Week 24
measure: Mean Percentage of Participants With BCVA ≥84 Letters (20/20 or Better) at Week 24, in Previously Treated Participants
timeFrame: Week 24
measure: Mean Percentage of Participants With BCVA ≥84 Letters (20/20 or Better) at Week 24, in All Participants
timeFrame: Week 24
measure: Mean Change From Baseline in Foveal Center Point Thickness at Week 24, in Treatment-Naive Participants
timeFrame: Baseline, Week 24
measure: Mean Change From Baseline in Foveal Center Point Thickness at Week 24, in Previously Treated Participants
timeFrame: Baseline, Week 24
measure: Mean Change From Baseline in Foveal Center Point Thickness at Week 24, in All Participants
timeFrame: Baseline, Week 24
measure: Mean Change From Baseline in Central Subfield Thickness at Week 24, in Treatment-Naive Participants
timeFrame: Baseline, Week 24
measure: Mean Change From Baseline in Central Subfield Thickness at Week 24, in Previously Treated Participants
timeFrame: Baseline, Week 24
measure: Mean Change From Baseline in Central Subfield Thickness at Week 24, in All Participants
timeFrame: Baseline, Week 24
measure: Percentage of Participants With Presence of Subretinal Fluid in the Study Eye at Week 24, in Treatment-Naive Participants
timeFrame: Week 24
measure: Percentage of Participants With Presence of Subretinal Fluid in the Study Eye at Week 24, in Previously Treated Participants
timeFrame: Week 24
measure: Percentage of Participants With Presence of Intraretinal Fluid in the Study Eye at Week 24, in Treatment-Naive Participants
timeFrame: Week 24
measure: Percentage of Participants With Presence of Intraretinal Fluid in the Study Eye at Week 24, in Previously Treated Participants
timeFrame: Week 24
measure: Number of Participants With Presence or Absence of Leakage at the Macula at Week 24, in Treatment-Naive Participants
timeFrame: Week 24
measure: Number of Participants With Presence or Absence of Leakage at the Macula at Week 24, in Previously Treated Participants
timeFrame: Week 24
measure: Mean Change From Baseline in the Size of the Foveal Avascular Zone at Week 24, in All Participants
timeFrame: Baseline, Week 24
measure: Mean Plasma Concentrations of Ranibizumab (Arm A) or Faricimab (Arms B and C) Over Time, in All Participants
timeFrame: Predose at Baseline and Weeks 1, 4, 12, 20, 24, 26, 28, 32, and 36
measure: Baseline and Change From Baseline in Free Vascular Endothelial Growth Factor (VEGF) Plasma Levels Over Time, in Treatment-Naive Participants
timeFrame: Baseline and Weeks 1, 4, 12, 16, 24, 26, 28, 32, and 36
measure: Baseline and Change From Baseline in Free Vascular Endothelial Growth Factor (VEGF) Plasma Levels Over Time, in Previously Treated Participants
timeFrame: Baseline and Weeks 1, 4, 12, 16, 24, 26, 28, 32, and 36
measure: Baseline and Change From Baseline in Total Angiopoietin-2 (Ang-2) Plasma Levels Over Time, in Treatment-Naive Participants
timeFrame: Baseline and Weeks 1, 4, 12, 16, 24, 26, 28, 32, and 36
measure: Baseline and Change From Baseline in Free Angiopoietin-2 (Ang-2) Plasma Levels Over Time, in Treatment-Naive Participants
timeFrame: Baseline and Weeks 1, 4, 12, 16, 24, 26, 28, 32, and 36
measure: Baseline and Change From Baseline in Total Angiopoietin-2 (Ang-2) Plasma Levels Over Time, in Previously Treated Participants
timeFrame: Baseline and Weeks 1, 4, 12, 16, 24, 26, 28, 32, and 36
measure: Baseline and Change From Baseline in Free Angiopoietin-2 (Ang-2) Plasma Levels Over Time, in Previously Treated Participants
timeFrame: Baseline and Weeks 1, 4, 12, 16, 24, 26, 28, 32, and 36
measure: Safety Summary of the Number of Participants With at Least One Adverse Event During the Treatment Period (up to Week 24), in All Participants
timeFrame: From Baseline up to Week 24
measure: Safety Summary of the Number of Participants With at Least One Adverse Event During the Post-Treatment Observation Period, in All Participants
timeFrame: From Week 24 up to Week 36
measure: Number of Participants With at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye During the Treatment Period by Highest Intensity, in All Participants
timeFrame: From Baseline up to Week 24
measure: Number of Participants With at Least One Systemic Adverse Event During the Treatment Period by Highest Intensity, in All Participants
timeFrame: From Baseline up to Week 24
measure: Number of Participants With Abnormal Systolic Blood Pressure Over Time, in All Participants
timeFrame: Baseline and Weeks 1, 4, 8, 12, 16, 20, 24, 26, 28, 32, and 36
measure: Number of Participants With Abnormal Diastolic Blood Pressure Over Time, in All Participants
timeFrame: Baseline and Weeks 1, 4, 8, 12, 16, 20, 24, 26, 28, 32, and 36
measure: Number of Participants With an Abnormal Heart Rate Over Time, in All Participants
timeFrame: Baseline and Weeks 1, 4, 8, 12, 16, 20, 24, 26, 28, 32, and 36
measure: Number of Participants With Abnormal Body Temperature Over Time, in All Participants
timeFrame: Baseline and Weeks 1, 4, 8, 12, 16, 20, 24, 26, 28, 32, and 36
measure: Mean Heart Rate at Baseline and Week 24, as Measured by Electrocardiogram in All Participants
timeFrame: Baseline, Week 24
measure: Mean PR, RR, QT, QRS, QTcB, and QTcF Intervals at Baseline and Week 24, as Measured by Electrocardiogram in All Participants
timeFrame: Baseline, Week 24
measure: Number of Participants With Marked Laboratory Abnormalities in Hematology Tests, in All Participants
timeFrame: Predose at Baseline, Weeks 12 and 24, and at Early Termination and Unscheduled Visits (up to 36 weeks)
measure: Number of Participants With Marked Laboratory Abnormalities in Blood Chemistry Tests, in All Participants
timeFrame: Predose at Baseline, Weeks 12 and 24, and at Early Termination and Unscheduled Visits (up to 36 weeks)
measure: Number of Participants With Marked Laboratory Abnormalities in Coagulation Tests, in All Participants
timeFrame: Predose at Baseline, Weeks 12 and 24, and at Early Termination and Unscheduled Visits (up to 36 weeks)
measure: Number of Participants Who Tested Negative or Positive for Anti-Drug Antibodies Against Faricimab Over Time
timeFrame: Baseline and Weeks 1, 4, 12, 16, 20, 24, 26, 28, 32, and 36
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Retinal Research Institute, LLC
state: Arizona
city: Phoenix
country: United States
facility: Associated Retina Consultants
state: Arizona
city: Phoenix
country: United States
facility: Arizona Retina and Vitreous Consultants
state: Arizona
city: Tucson
country: United States
facility: Retina Associates Southwest PC
state: Arizona
city: Fullerton
country: United States
facility: Retina Consultants of Orange County
state: California
city: Inglewood
country: United States
facility: United Med Res Inst
state: California
city: Mountain View
country: United States
facility: Northern California Retina Vitreous Associates
state: California
city: Oceanside
country: United States
facility: Ophthalmic Clinical Trials San Diego
state: California
city: Palm Desert
country: United States
facility: Southern CA Desert Retina Cons
state: California
city: Poway
country: United States
facility: Retina Consultants, San Diego
state: California
city: Sacramento
country: United States
facility: Retinal Consultants Med Group
state: California
city: Santa Barbara
country: United States
facility: California Retina Consultants
state: California
city: Walnut Creek
country: United States
facility: Bay Area Retina Associates
state: California
city: Colorado Springs
country: United States
facility: Retina Consultants of Southern
state: Colorado
city: Deerfield Beach
country: United States
facility: Rand Eye
state: Florida
city: Fort Myers
country: United States
facility: National Ophthalmic Research Institute
state: Florida
city: Melbourne
country: United States
facility: Florida Eye Associates
state: Florida
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: Augusta
country: United States
facility: Southeast Retina Center
state: Georgia
city: Marietta
country: United States
facility: Georgia Retina PC
state: Georgia
city: Chicago
country: United States
facility: Univ of Illinois at Chicago
state: Illinois
city: Oak Forest
country: United States
facility: University Retina and Macula Associates, PC
state: Illinois
city: Oak Park
country: United States
facility: Illinois Retina Associates SC
state: Illinois
city: Indianapolis
country: United States
facility: Midwest Eye Institute
state: Indiana
city: West Des Moines
country: United States
facility: Wolfe Eye Clinic
state: Iowa
city: Lexington
country: United States
facility: Retina Associates of Kentucky
state: Kentucky
city: Paducah
country: United States
facility: Paducah Retinal Center
state: Kentucky
city: Baltimore
country: United States
facility: Wilmer Eye Institute
state: Maryland
city: Grand Rapids
country: United States
facility: Vitreo-Retinal Associates
state: Michigan
city: Edina
country: United States
facility: Vitreoretinal Surgery
state: Minnesota
city: Reno
country: United States
facility: Sierra Eye Associates
state: Nevada
city: Bloomfield
country: United States
facility: Retina Center of New Jersey
state: New Jersey
city: Albuquerque
country: United States
facility: Eye Associates of New Mexico
state: New Mexico
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Albany
country: United States
facility: Capital Region Retina
state: New York
city: Lynbrook
country: United States
facility: Opthalmic Consultants of LI
state: New York
city: Orchard Park
country: United States
facility: Retina Consultants of Western New York
state: New York
city: Asheville
country: United States
facility: Western Carolina Retinal Associate PA
state: North Carolina
city: Charlotte
country: United States
facility: Char Eye Ear &Throat Assoc
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation; Cole Eye Institute
state: Ohio
city: Columbus
country: United States
facility: OSU Eye Physicians & Surgeons
state: Ohio
city: Eugene
country: United States
facility: Oregon Retina, LLP
state: Oregon
city: Portland
country: United States
facility: Retina Northwest
state: Oregon
city: Florence
country: United States
facility: Palmetto Retina Center
state: South Carolina
city: Ladson
country: United States
facility: Charleston Neuroscience Inst
state: South Carolina
city: Germantown
country: United States
facility: Charles Retina Institute
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Retina PC.
state: Tennessee
city: Abilene
country: United States
facility: W Texas Retina Consultants PA
state: Texas
city: Austin
country: United States
facility: Austin Retina Associates
state: Texas
city: Austin
country: United States
facility: Retina Consultants of Austin
state: Texas
city: DeSoto
country: United States
facility: Retina Specialists
state: Texas
city: Houston
country: United States
facility: Retina Consultants of Houston
state: Texas
city: San Antonio
country: United States
facility: Med Center Ophthalmology Assoc
state: Texas
city: The Woodlands
country: United States
facility: Retina Consultants of Houston
state: Texas
city: Salt Lake City
country: United States
facility: Retina Associates of Utah
state: Utah
city: Charlottesville
country: United States
facility: Univ of Virginia Ophthalmology
state: Virginia
city: Spokane
country: United States
facility: Spokane Eye Clinical Research
state: Washington
city: Morgantown
country: United States
facility: West Virginia University Eye Institute
state: West Virginia
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Sahni J, Patel SS, Dugel PU, Khanani AM, Jhaveri CD, Wykoff CC, Hershberger VS, Pauly-Evers M, Sadikhov S, Szczesny P, Schwab D, Nogoceke E, Osborne A, Weikert R, Fauser S. Simultaneous Inhibition of Angiopoietin-2 and Vascular Endothelial Growth Factor-A with Faricimab in Diabetic Macular Edema: BOULEVARD Phase 2 Randomized Trial. Ophthalmology. 2019 Aug;126(8):1155-1170. doi: 10.1016/j.ophtha.2019.03.023. Epub 2019 Mar 21.