A Study of Faricimab (RO6867461) in Participants With Center-Involving Diabetic Macular Edema (BOULEVARD)

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetic Macular Edema
• Intervention / Treatment: Drug: Ranibizumab; Drug: Faricimab

• Study Type: Interventional
• Enrollment (Actual): 229
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85014
      • Retinal Research Institute, LLC
    • Phoenix, Arizona, United States, 85021
      • Arizona Retina and Vitreous Consultants
    • Phoenix, Arizona, United States, 85020
      • Associated Retina Consultants
    • Tucson, Arizona, United States, 85750
      • Retina Associates Southwest PC
  • California
    • Fullerton, California, United States, 92835
      • Retina Consultants of Orange County
    • Inglewood, California, United States, 90301
      • United Med Res Inst
    • Mountain View, California, United States, 94040
      • Northern California Retina Vitreous Associates
    • Oceanside, California, United States, 92056
      • Ophthalmic Clinical Trials San Diego
    • Palm Desert, California, United States, 92211
      • Southern CA Desert Retina Cons
    • Poway, California, United States, 92064
      • Retina Consultants, San Diego
    • Sacramento, California, United States, 95825
      • Retinal Consultants Med Group
    • Santa Barbara, California, United States, 93103
      • California Retina Consultants
    • Walnut Creek, California, United States, 94598
      • Bay Area Retina Associates
  • Colorado
    • Colorado Springs, Colorado, United States, 80909
      • Retina Consultants of Southern
  • Florida
    • Deerfield Beach, Florida, United States, 33064
      • Rand Eye
    • Fort Myers, Florida, United States, 33912
      • National Ophthalmic Research Institute
    • Melbourne, Florida, United States, 32901
      • Florida Eye Associates
    • Pensacola, Florida, United States, 32503
      • Retina Specialty Institute
    • Saint Petersburg, Florida, United States, 33711
      • Retina Vitreous Assoc of FL
    • Tallahassee, Florida, United States, 32308
      • Southern Vitreoretinal Assoc
  • Georgia
    • Augusta, Georgia, United States, 30909
      • Southeast Retina Center
    • Marietta, Georgia, United States, 30060
      • Georgia Retina PC
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Univ of Illinois at Chicago
    • Oak Forest, Illinois, United States, 60452
      • University Retina and Macula Associates, PC
    • Oak Park, Illinois, United States, 60304
      • Illinois Retina Associates SC
  • Indiana
    • Indianapolis, Indiana, United States, 46290
      • Midwest Eye Institute
  • Iowa
    • West Des Moines, Iowa, United States, 50266
      • Wolfe Eye Clinic
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • Retina Associates of Kentucky
    • Paducah, Kentucky, United States, 42001
      • Paducah Retinal Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Wilmer Eye Institute
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Vitreo-Retinal Associates
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Vitreoretinal Surgery
  • Nevada
    • Reno, Nevada, United States, 89502
      • Sierra Eye Associates
  • New Jersey
    • Bloomfield, New Jersey, United States, 07003
      • Retina Center of New Jersey
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Eye Associates of New Mexico
  • New York
    • Albany, New York, United States, 12206
      • Capital Region Retina
    • Lynbrook, New York, United States, 11563
      • Opthalmic Consultants of LI
    • Orchard Park, New York, United States, 14127
      • Retina Consultants of Western New York
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Western Carolina Retinal Associate PA
    • Charlotte, North Carolina, United States, 28210
      • Char Eye Ear &Throat Assoc
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation; Cole Eye Institute
    • Columbus, Ohio, United States, 43212
      • OSU Eye Physicians & Surgeons
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Oregon Retina, LLP
    • Portland, Oregon, United States, 97221
      • Retina Northwest
  • South Carolina
    • Florence, South Carolina, United States, 29501
      • Palmetto Retina Center
    • Ladson, South Carolina, United States, 29456
      • Charleston Neuroscience Inst
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Charles Retina Institute
    • Nashville, Tennessee, United States, 37203
      • Tennessee Retina PC.
  • Texas
    • Abilene, Texas, United States, 79606
      • W Texas Retina Consultants PA
    • Austin, Texas, United States, 78705
      • Austin Retina Associates
    • Austin, Texas, United States, 78705
      • Retina Consultants of Austin
    • DeSoto, Texas, United States, 75115
      • Retina Specialists
    • Houston, Texas, United States, 77030
      • Retina Consultants of Houston
    • San Antonio, Texas, United States, 78240
      • Med Center Ophthalmology Assoc
    • The Woodlands, Texas, United States, 77384
      • Retina Consultants of Houston
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Retina Associates of Utah
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Univ of Virginia Ophthalmology
  • Washington
    • Spokane, Washington, United States, 99204
      • Spokane Eye Clinical Research
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University Eye Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A: 0.3 mg Ranibizumab; Participants will receive 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant meets pre-specified criteria the participant will receive a single dose of 0.3 mg ranibizumab and exit the study.	Drug: Ranibizumab; Ranibizumab will be administered by IVT injection in the study eye.; Other Names: Lucentis
Experimental: Arm B: 1.5 mg Faricimab; Participants will receive 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant meets pre-specified criteria the participant will receive a single dose of 0.3 mg ranibizumab and exit the study.	Drug: Faricimab; Faricimab will be administered by IVT injection in the study eye.; Other Names: RO6867461; RG7716
Experimental: Arm C: 6 mg Faricimab; Participants will receive 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant meets pre-specified criteria the participant will receive a single dose of 0.3 mg ranibizumab and exit the study.	Drug: Faricimab; Faricimab will be administered by IVT injection in the study eye.; Other Names: RO6867461; RG7716

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in BCVA Letter Score at Week 24, in Treatment-Naive Participants	Best corrected visual acuity (BCVA) at a starting test distance of 4 meters was measured using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity examiner masked to study drug arm assignment. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment, but was not allowed to perform any other tasks involving direct care. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the participant's refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The primary analysis used a Linear Mixed Effects Model for Repeated Measurements. Missing values were not imputed; it was assumed that the data were missing at random.	Baseline, Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in BCVA Letter Score at Week 24, in Previously Treated Participants	Best corrected visual acuity (BCVA) at a starting test distance of 4 meters was measured using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity examiner masked to study drug arm assignment. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment, but was not allowed to perform any other tasks involving direct care. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the participant's refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The primary analysis used a Linear Mixed Effects Model for Repeated Measurements. Missing values were not imputed; it was assumed that the data were missing at random.	Baseline, Week 24
Mean Change From Baseline in BCVA Letter Score at Week 24, in All Participants	Best corrected visual acuity (BCVA) at a starting test distance of 4 meters was measured using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity examiner masked to study drug arm assignment. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment, but was not allowed to perform any other tasks involving direct care. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the participant's refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The primary analysis used a Linear Mixed Effects Model for Repeated Measurements. Missing values were not imputed; it was assumed that the data were missing at random.	Baseline, Week 24
Mean Percentage of Participants Who Gained ≥15 ETDRS Letters From Baseline BCVA Score at Week 24, in Treatment-Naive Participants	Best corrected visual acuity (BCVA) at a starting test distance of 4 meters was measured using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity examiner masked to study drug arm assignment. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment, but was not allowed to perform any other tasks involving direct care. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the participant's refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The outcome measure was analyzed using a Generalized Estimating Equations Model. Missing values were not imputed; it was assumed that the data were missing at random.	Baseline, Week 24
Mean Percentage of Participants Who Gained ≥15 ETDRS Letters From Baseline BCVA Score at Week 24, in Previously Treated Participants	Best corrected visual acuity (BCVA) at a starting test distance of 4 meters was measured using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity examiner masked to study drug arm assignment. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment, but was not allowed to perform any other tasks involving direct care. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the participant's refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The outcome measure was analyzed using a Generalized Estimating Equations Model. Missing values were not imputed; it was assumed that the data were missing at random.	Baseline up to Week 24
Mean Percentage of Participants Who Gained ≥15 ETDRS Letters From Baseline BCVA Score at Week 24, in All Participants	Best corrected visual acuity (BCVA) at a starting test distance of 4 meters was measured using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity examiner masked to study drug arm assignment. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment, but was not allowed to perform any other tasks involving direct care. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the participant's refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The outcome measure was analyzed using a Generalized Estimating Equations Model. Missing values were not imputed; it was assumed that the data were missing at random.	Baseline up to Week 24
Mean Percentage of Participants With BCVA ≥69 Letters (20/40 or Better) at Week 24, in Treatment-Naive Participants	Best corrected visual acuity (BCVA) at a starting test distance of 4 meters was measured using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity examiner masked to study drug arm assignment. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment, but was not allowed to perform any other tasks involving direct care. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the participant's refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The outcome measure was analyzed using a Generalized Estimating Equations Model. Missing values were not imputed; it was assumed that the data were missing at random.	Week 24
Mean Percentage of Participants With BCVA ≥69 Letters (20/40 or Better) at Week 24, in Previously Treated Participants	Best corrected visual acuity (BCVA) at a starting test distance of 4 meters was measured using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity examiner masked to study drug arm assignment. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment, but was not allowed to perform any other tasks involving direct care. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the participant's refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The outcome measure was analyzed using a Generalized Estimating Equations Model. Missing values were not imputed; it was assumed that the data were missing at random.	Week 24
Mean Percentage of Participants With BCVA ≥69 Letters (20/40 or Better) at Week 24, in All Participants	Best corrected visual acuity (BCVA) at a starting test distance of 4 meters was measured using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity examiner masked to study drug arm assignment. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment, but was not allowed to perform any other tasks involving direct care. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the participant's refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The outcome measure was analyzed using a Generalized Estimating Equations Model. Missing values were not imputed; it was assumed that the data were missing at random.	Week 24
Mean Percentage of Participants With BCVA ≥84 Letters (20/20 or Better) at Week 24, in Treatment-Naive Participants	Best corrected visual acuity (BCVA) at a starting test distance of 4 meters was measured using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity examiner masked to study drug arm assignment. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment, but was not allowed to perform any other tasks involving direct care. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the participant's refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The outcome measure was analyzed using a Generalized Estimating Equations Model. Missing values were not imputed; it was assumed that the data were missing at random.	Week 24
Mean Percentage of Participants With BCVA ≥84 Letters (20/20 or Better) at Week 24, in Previously Treated Participants	Best corrected visual acuity (BCVA) at a starting test distance of 4 meters was measured using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity examiner masked to study drug arm assignment. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment, but was not allowed to perform any other tasks involving direct care. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the participant's refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The outcome measure was analyzed using a Generalized Estimating Equations Model. Missing values were not imputed; it was assumed that the data were missing at random.	Week 24
Mean Percentage of Participants With BCVA ≥84 Letters (20/20 or Better) at Week 24, in All Participants	Best corrected visual acuity (BCVA) at a starting test distance of 4 meters was measured using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity examiner masked to study drug arm assignment. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment, but was not allowed to perform any other tasks involving direct care. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the participant's refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The outcome measure was analyzed using a Generalized Estimating Equations Model. Missing values were not imputed; it was assumed that the data were missing at random.	Week 24
Mean Change From Baseline in Foveal Center Point Thickness at Week 24, in Treatment-Naive Participants	Foveal center point thickness (FCPT) is defined as the thickness from the inner limiting membrane to the retinal pigment epithelial at the horizontal slice closest to the center of the fovea. Foveal center point thickness was measured using spectral domain optical coherence tomography (SD-OCT).	Baseline, Week 24
Mean Change From Baseline in Foveal Center Point Thickness at Week 24, in Previously Treated Participants	Foveal center point thickness (FCPT) is defined as the thickness from the inner limiting membrane to the retinal pigment epithelial at the horizontal slice closest to the center of the fovea. Foveal center point thickness was measured using spectral domain optical coherence tomography (SD-OCT).	Baseline, Week 24
Mean Change From Baseline in Foveal Center Point Thickness at Week 24, in All Participants	Foveal center point thickness (FCPT) is defined as the thickness from the inner limiting membrane to the retinal pigment epithelial at the horizontal slice closest to the center of the fovea. Foveal center point thickness was measured using spectral domain optical coherence tomography (SD-OCT).	Baseline, Week 24
Mean Change From Baseline in Central Subfield Thickness at Week 24, in Treatment-Naive Participants	Central subfield thickness (CST) is defined as the mean thickness from the inner limiting membrane to the retinal pigment epithelial over the 1 millimetre (mm) central subfield. Central subfield thickness was measured using SD-OCT.	Baseline, Week 24
Mean Change From Baseline in Central Subfield Thickness at Week 24, in Previously Treated Participants	Central subfield thickness (CST) is defined as the mean thickness from the inner limiting membrane to the retinal pigment epithelial over the 1 millimetre (mm) central subfield. Central subfield thickness was measured using SD-OCT.	Baseline, Week 24
Mean Change From Baseline in Central Subfield Thickness at Week 24, in All Participants	Central subfield thickness (CST) is defined as the mean thickness from the inner limiting membrane to the retinal pigment epithelial over the 1 millimetre (mm) central subfield. Central subfield thickness was measured using SD-OCT.	Baseline, Week 24
Percentage of Participants With Presence of Subretinal Fluid in the Study Eye at Week 24, in Treatment-Naive Participants	Subretinal fluid is defined as the presence of fluid between the retina and the retinal pigment epithelium. Resolution of subretinal fluid was measured using SD-OCT.	Week 24
Percentage of Participants With Presence of Subretinal Fluid in the Study Eye at Week 24, in Previously Treated Participants	Subretinal fluid is defined as the presence of fluid between the retina and the retinal pigment epithelium. Resolution of subretinal fluid was measured using SD-OCT.	Week 24
Percentage of Participants With Presence of Intraretinal Fluid in the Study Eye at Week 24, in Treatment-Naive Participants	Intraretinal fluid is described as the presence of fluid within the retina. Resolution of intraretinal fluid was measured by SD-OCT.	Week 24
Percentage of Participants With Presence of Intraretinal Fluid in the Study Eye at Week 24, in Previously Treated Participants	Intraretinal fluid is described as the presence of fluid within the retina. Resolution of intraretinal fluid was measured by SD-OCT.	Week 24
Number of Participants With Presence or Absence of Leakage at the Macula at Week 24, in Treatment-Naive Participants	Leakage at the macula describes the leakage of fluorescein at the macula region as measured by fundus fluorescein angiography (FFA).	Week 24
Number of Participants With Presence or Absence of Leakage at the Macula at Week 24, in Previously Treated Participants	Leakage at the macula describes the leakage of fluorescein at the macula region as measured by fundus fluorescein angiography (FFA).	Week 24
Mean Change From Baseline in the Size of the Foveal Avascular Zone at Week 24, in All Participants	The size of the foveal avascular zone was to be measured by fundus fluorescein angiography (FFA).	Baseline, Week 24
Mean Plasma Concentrations of Ranibizumab (Arm A) or Faricimab (Arms B and C) Over Time, in All Participants	Plasma concentrations of ranibizumab were measured by an appropriate assay only from samples of participants randomized to Arm A: 0.3 mg Ranibizumab. Plasma concentrations of faricimab were measured by a specific validated enzyme-linked immunoabsorbent assay (ELISA) only from samples of participants randomized to Arm B: 1.5 mg Faricimab and Arm C: 6 mg Faricimab. Baseline was defined as the last non-missing predose assessment. The lower limit of quantification (LLOQ) for the ranibizumab and faricimab assays were 0.015 nanograms per millilitre (ng/mL) and 0.800 ng/mL, respectively. Values below the limit of quantification were imputed as LLOQ divided by 2.	Predose at Baseline and Weeks 1, 4, 12, 20, 24, 26, 28, 32, and 36
Baseline and Change From Baseline in Free Vascular Endothelial Growth Factor (VEGF) Plasma Levels Over Time, in Treatment-Naive Participants	The concentration of free VEGF was determined in plasma samples using an enzyme-linked immunosorbent assay (ELISA) method. The lower limit of quantification (LLOQ) of the assay was 15.6 picograms per millilitre (pg/mL). Plasma free VEGF concentrations below the limit of quantification were imputed as LLOQ divided by 2.	Baseline and Weeks 1, 4, 12, 16, 24, 26, 28, 32, and 36
Baseline and Change From Baseline in Free Vascular Endothelial Growth Factor (VEGF) Plasma Levels Over Time, in Previously Treated Participants	The concentration of free VEGF was determined in plasma samples using an enzyme-linked immunosorbent assay (ELISA) method. The lower limit of quantification (LLOQ) of the assay was 15.6 picograms per millilitre (pg/mL). Plasma free VEGF concentrations below the limit of quantification were imputed as LLOQ divided by 2.	Baseline and Weeks 1, 4, 12, 16, 24, 26, 28, 32, and 36
Baseline and Change From Baseline in Total Angiopoietin-2 (Ang-2) Plasma Levels Over Time, in Treatment-Naive Participants	Total Ang-2 concentrations were determined in plasma samples using an appropriate assay method. The lower limit of quantification (LLOQ) of the assay was 0.09 nanograms per millilitre (ng/mL). Plasma total Ang-2 concentrations below the limit of quantification were imputed as LLOQ divided by 2.	Baseline and Weeks 1, 4, 12, 16, 24, 26, 28, 32, and 36
Baseline and Change From Baseline in Free Angiopoietin-2 (Ang-2) Plasma Levels Over Time, in Treatment-Naive Participants	Free Ang-2 concentrations were determined in plasma samples using an appropriate assay method. The lower limit of quantification (LLOQ) of the assay was 0.9 nanograms per millilitre (ng/mL). Plasma free Ang-2 concentrations below the limit of quantification were imputed as LLOQ divided by 2.	Baseline and Weeks 1, 4, 12, 16, 24, 26, 28, 32, and 36
Baseline and Change From Baseline in Total Angiopoietin-2 (Ang-2) Plasma Levels Over Time, in Previously Treated Participants	Total Ang-2 concentrations were determined in plasma samples using an appropriate assay method. The lower limit of quantification (LLOQ) of the assay was 0.09 nanograms per millilitre (ng/mL). Plasma total Ang-2 concentrations below the limit of quantification were imputed as LLOQ divided by 2.	Baseline and Weeks 1, 4, 12, 16, 24, 26, 28, 32, and 36
Baseline and Change From Baseline in Free Angiopoietin-2 (Ang-2) Plasma Levels Over Time, in Previously Treated Participants	Free Ang-2 concentrations were determined in plasma samples using an appropriate assay method. The lower limit of quantification (LLOQ) of the assay was 0.9 nanograms per millilitre (ng/mL). Plasma free Ang-2 concentrations below the limit of quantification were imputed as LLOQ divided by 2.	Baseline and Weeks 1, 4, 12, 16, 24, 26, 28, 32, and 36
Safety Summary of the Number of Participants With at Least One Adverse Event During the Treatment Period (up to Week 24), in All Participants	This safety summary reports the number and percentage of participants who experienced at least one adverse event (AE) within 28 days of the end of the treatment period (i.e., up to Week 24). AEs are categorized as any AEs, ocular AEs occurring in the study eye or fellow eye, systemic AEs, serious AEs, AEs related to treatment with study drug, AEs leading to discontinuation of treatment with study drug, and AEs with fatal outcome. Multiple occurrences of the same AE in one individual were counted only once.	From Baseline up to Week 24
Safety Summary of the Number of Participants With at Least One Adverse Event During the Post-Treatment Observation Period, in All Participants	This safety summary reports the number and percentage of participants who experienced at least one adverse event (AE) during the post-treatment observation period (i.e., from Week 24 up to Week 36). AEs are categorized as any AEs, ocular AEs occurring in the study eye or fellow eye, systemic AEs, serious AEs, AEs related to treatment with study drug, AEs leading to discontinuation of treatment with study drug, and AEs with fatal outcome. Multiple occurrences of the same AE in one individual were counted only once.	From Week 24 up to Week 36
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	The investigator assessed adverse event severity according to the following grading scale: Mild = Discomfort noticed, but no disruption of normal daily activity; Moderate = Discomfort sufficient to reduce or affect normal daily activity; Severe = Incapacitating with inability to work or to perform normal daily activity. Only the most severe intensity was counted for multiple occurrences of the same adverse event per participant at the preferred term level. Severity and seriousness are not synonymous; regardless of severity, some adverse events may have also met seriousness criteria.	From Baseline up to Week 24
Number of Participants With at Least One Systemic Adverse Event During the Treatment Period by Highest Intensity, in All Participants	The investigator assessed adverse event severity according to the following grading scale: Mild = Discomfort noticed, but no disruption of normal daily activity; Moderate = Discomfort sufficient to reduce or affect normal daily activity; Severe = Incapacitating with inability to work or to perform normal daily activity. Only the most severe intensity was counted for multiple occurrences of the same adverse event per participant at the preferred term level. Severity and seriousness are not synonymous; regardless of severity, some adverse events may have also met seriousness criteria.	From Baseline up to Week 24
Number of Participants With Abnormal Systolic Blood Pressure Over Time, in All Participants	Abnormal systolic blood pressure (supine) was defined as any value outside of the standard reference range, from <70 (low) to >180 (high) millimetres of mercury (mmHg) or a change from baseline of greater than 30 mmHg (decrease or increase). Baseline was defined as the last non-missing predose assessment. Not every abnormal vital sign qualified as an adverse event, only if it met any of the following criteria: clinically significant (per investigator); accompanied by clinical symptoms; resulted in a change in study treatment; or required a change in concomitant therapy.	Baseline and Weeks 1, 4, 8, 12, 16, 20, 24, 26, 28, 32, and 36
Number of Participants With Abnormal Diastolic Blood Pressure Over Time, in All Participants	Abnormal diastolic blood pressure (supine) was defined as any value outside of the standard reference range, from <40 (low) to >110 (high) millimetres of mercury (mmHg) or a change from baseline of greater than 20 mmHg (decrease or increase). Baseline was defined as the last non-missing predose assessment. Not every abnormal vital sign qualified as an adverse event, only if it met any of the following criteria: clinically significant (per investigator); accompanied by clinical symptoms; resulted in a change in study treatment; or required a change in concomitant therapy.	Baseline and Weeks 1, 4, 8, 12, 16, 20, 24, 26, 28, 32, and 36
Number of Participants With an Abnormal Heart Rate Over Time, in All Participants	Abnormal heart rate (supine) was defined as any value outside of the standard reference range, from <40 (low) to >100 (high) beats per minute. Baseline was defined as the last non-missing predose assessment. Not every abnormal vital sign qualified as an adverse event, only if it met any of the following criteria: clinically significant (per investigator); accompanied by clinical symptoms; resulted in a change in study treatment; or required a change in concomitant therapy.	Baseline and Weeks 1, 4, 8, 12, 16, 20, 24, 26, 28, 32, and 36
Number of Participants With Abnormal Body Temperature Over Time, in All Participants	Abnormal body temperature (supine) was defined as any value outside of the standard reference range, from <36.5 (low) to >37.5 (high) degrees Celsius. Baseline was defined as the last non-missing predose assessment. Not every abnormal vital sign qualified as an adverse event, only if it met any of the following criteria: clinically significant (per investigator); accompanied by clinical symptoms; resulted in a change in study treatment; or required a change in concomitant therapy.	Baseline and Weeks 1, 4, 8, 12, 16, 20, 24, 26, 28, 32, and 36
Mean Heart Rate at Baseline and Week 24, as Measured by Electrocardiogram in All Participants	Triplicate 12-lead electrocardiogram (ECG), i.e., three useful ECGs without artifacts, were performed on all evaluable participants. To minimize variability, it was important that participants be in a resting position for at least 10 minutes prior to the ECG evaluation. Body position was to be consistently maintained for each ECG evaluation to prevent changes in heart rate. Environmental distractions (e.g., television, radio, conversation, mobile phones) were to be minimized before and during ECG recording. Triplicate ECGs were to be obtained within a 5-minute interval. The predefined standard reference range for heart rate measured by ECG was 40 (low) to 100 (high) beats per minute.	Baseline, Week 24
Mean PR, RR, QT, QRS, QTcB, and QTcF Intervals at Baseline and Week 24, as Measured by Electrocardiogram in All Participants	Triplicate 12-lead electrocardiogram (ECG), i.e., three useful ECGs without artifacts, were performed on all evaluable participants. To minimize variability, it was important that participants be in a resting position for at least 10 minutes prior to the ECG evaluation. Body position was to be consistently maintained for each ECG evaluation to prevent changes in heart rate. Environmental distractions (e.g., television, radio, conversation, mobile phones) were to be minimized before and during ECG recording. Triplicate ECGs were to be obtained within a 5-minute interval. Baseline was defined as the last non-missing predose assessment. The predefined standard reference ranges for the intervals measured by ECG were defined as follows (ranges are from low to high, in milliseconds [msec]): PR: 120-200 msec; RR: 600-1500 msec; QT: 200-500 msec; QRS: 40-120 msec.	Baseline, Week 24
Number of Participants With Marked Laboratory Abnormalities in Hematology Tests, in All Participants	Clinical laboratory tests for hematology parameters were performed and any marked abnormal values (High or Low) were based on Roche's predefined standard reference ranges. Marked laboratory abnormalities are presented according to COG3007 abnormality criteria: Single, Not Last = abnormality detected at a single assessment, but not at the last assessment; Last or Replicated = abnormality detected at the last assessment or replicated at one or more assessments. Not every laboratory abnormality qualified as an adverse event, only if it met any of the following criteria: clinically significant (per investigator); accompanied by clinical symptoms; resulted in a change in study treatment; or required a change in concomitant therapy. Abs. = absolute count; Ery. = erythrocyte; Hemo. = hemoglobin	Predose at Baseline, Weeks 12 and 24, and at Early Termination and Unscheduled Visits (up to 36 weeks)
Number of Participants With Marked Laboratory Abnormalities in Blood Chemistry Tests, in All Participants	Clinical laboratory tests for blood chemistry parameters were performed and any marked abnormal values (High or Low) were based on Roche's predefined standard reference ranges. Marked laboratory abnormalities are presented according to COG3007 abnormality criteria: Single, Not Last = abnormality detected at a single assessment, but not at the last assessment; Last or Replicated = abnormality detected at the last assessment or replicated at one or more assessments. Not every laboratory abnormality qualified as an adverse event, only if it met any of the following criteria: clinically significant (per investigator); accompanied by clinical symptoms; resulted in a change in study treatment; or required a change in concomitant therapy. SGOT/AST = serum glutamic oxaloacetic transaminase / aspartate aminotransferase	Predose at Baseline, Weeks 12 and 24, and at Early Termination and Unscheduled Visits (up to 36 weeks)
Number of Participants With Marked Laboratory Abnormalities in Coagulation Tests, in All Participants	Clinical laboratory tests for coagulation parameters were performed and any marked abnormal values (High or Low) were based on Roche's predefined standard reference ranges. Marked laboratory abnormalities are presented according to COG3007 abnormality criteria: Single, Not Last = abnormality detected at a single assessment, but not at the last assessment; Last or Replicated = abnormality detected at the last assessment or replicated at one or more assessments. Not every laboratory abnormality qualified as an adverse event, only if it met any of the following criteria: clinically significant (per investigator); accompanied by clinical symptoms; resulted in a change in study treatment; or required a change in concomitant therapy. aPTT = activated partial thromboplastin time; INR = International Normalized Ratio (prothrombin time)	Predose at Baseline, Weeks 12 and 24, and at Early Termination and Unscheduled Visits (up to 36 weeks)
Number of Participants Who Tested Negative or Positive for Anti-Drug Antibodies Against Faricimab Over Time	The number and percentage of participants who tested negative or positive for plasma anti-drug antibodies (ADA) to faricimab at baseline and at the study visits was tabulated, except for those who were randomized to treatment with ranibizumab in Arm A.	Baseline and Weeks 1, 4, 12, 16, 20, 24, 26, 28, 32, and 36

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2016
• Primary Completion (Actual): September 15, 2017
• Study Completion (Actual): December 14, 2017

Study Registration Dates

• First Submitted: March 1, 2016
• First Submitted That Met QC Criteria: March 1, 2016
• First Posted (Estimate): March 4, 2016

Study Record Updates

• Last Update Posted (Actual): September 25, 2020
• Last Update Submitted That Met QC Criteria: August 31, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Macular Edema; Edema; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Ranibizumab
• Other Study ID Numbers: BP30099; RG7716 (Other Identifier: Roche theme number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No