A Proof-of-Concept Study of Faricimab (RO6867461) in Participants With Choroidal Neovascularization (CNV) Secondary to Age-Related Macular Degeneration (AMD) (AVENUE)

A Multiple-Center, Multiple-Dose and Regimen, 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 Choroidal Neovascularization Secondary to Age-Related Macular Degeneration

This multiple-center, multiple-dose and regimen, randomized, double-masked active comparator-controlled, double-masked, five parallel group, 36-week study will evaluate the efficacy, safety, tolerability, and pharmacokinetics of faricimab (RO6867461) in participants with choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD).

The study was designed to allow the evaluation of RO6867461 in a treatment-naive population (comparison of Arms A, B, C, and D) and an anti-VEGF-incomplete responder population that met a predefined criterion at Week 12 (comparison between Arms A and E). Only one eye per participant was chosen as the study eye.

Study Overview

• Status: Completed
• Conditions: Choroidal Neovascularization
• Intervention / Treatment: Drug: Ranibizumab; Drug: Faricimab; Drug: Sham Procedure

• Study Type: Interventional
• Enrollment (Actual): 273
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85020
      • Associated Retina Consultants
    • Phoenix, Arizona, United States, 85053
      • Retinal Consultants of Arizona
  • California
    • Bakersfield, California, United States, 93309
      • California Retina Consultants
    • Beverly Hills, California, United States, 90211
      • Retina-Vitreous Associates Medical Group
    • Encino, California, United States, 91436
      • The Retina Partners
    • Poway, California, United States, 92064
      • Retina Consultants, San Diego
    • Santa Ana, California, United States, 92705
      • Orange County Retina Med Group
    • Walnut Creek, California, United States, 94598
      • Bay Area Retina Associates
    • Whittier, California, United States, 90603
      • American Institute of Research
  • Colorado
    • Colorado Springs, Colorado, United States, 80909
      • Retina Consultants of Southern
    • Golden, Colorado, United States, 80401
      • Colorado Retina Associates, PC
  • Connecticut
    • Hamden, Connecticut, United States, 06518
      • New England Retina Associates
  • Florida
    • Fort Myers, Florida, United States, 33912
      • National Ophthalmic Research Institute
    • Fort Myers, Florida, United States, 33907
      • Retina Health Center
    • Melbourne, Florida, United States, 32901
      • Florida Eye Associates
    • Orlando, Florida, United States, 32806
      • Central Florida Retina
    • Palm Beach Gardens, Florida, United States, 33410
      • Retina Care Specialists
    • 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
  • Indiana
    • Indianapolis, Indiana, United States, 46290
      • Midwest Eye Institute Northside
  • Kentucky
    • Paducah, Kentucky, United States, 42001
      • Paducah Retinal Center
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • Retina Group of Washington
    • Towson, Maryland, United States, 21204
      • National Retina Institute
  • Massachusetts
    • Worcester, Massachusetts, United States, 01605
      • Vitreo-Retinal Associates, PC
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • VitreoRetinal Surgery
  • New Jersey
    • Toms River, New Jersey, United States, 08755
      • Retina Associates of NJ
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Eye Associates of New Mexico
  • New York
    • Great Neck, New York, United States, 11021
      • Long Is. Vitreoretinal Consult
    • Lynbrook, New York, United States, 11563
      • Opthalmic Consultants of LI
    • Rochester, New York, United States, 14620
      • Retina Assoc of Western NY
    • Slingerlands, New York, United States, 12159
      • The Retina Consultants
  • 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
    • Columbus, Ohio, United States, 43212
      • OSU Eye Physicians & Surgeons
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Oregon Retina, LLP
    • Medford, Oregon, United States, 97504
      • Oregon Retina Institute
    • Portland, Oregon, United States, 97221
      • Retina Northwest
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Mid Atlantic Retina
  • South Carolina
    • West Columbia, South Carolina, United States, 29169
      • Palmetto Retina Center
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • Southeastern Retina Associates Chattanooga
    • 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 Research Center
    • Houston, Texas, United States, 77030
      • Retina Consultants of Houston
    • Willow Park, Texas, United States, 76087
      • Strategic Clinical Research Group, LLC
  • 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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Treatment-naive with CNV secondary to AMD, with subfoveal CNV or juxtafoveal CNV with a subfoveal component related to the CNV activity by FFA or SD-OCT
• Active CNV

Exclusion Criteria:

• CNV due to causes other than AMD
• Subretinal hemorrhage, fibrosis, or atrophy involving either the fovea or more than 50% of the total lesion area
• Cataract surgery within 3 months of baseline, or any other previous intraocular surgery
• Major illness or surgery within 1 month prior to Screening
• Glycosylated hemoglobin (HbA1c) above 7.5%
• Uncontrolled blood pressure

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W); Participants will receive ranibizumab, 0.5 milligrams (mg) intravitreal (IVT) Q4W up to Week 32 (total 9 injections). The final study visit will take place at Week 36.	Drug: Ranibizumab; Ranibizumab will be administered as per the regimen specified in the individual arm.; Other Names: Lucentis
Experimental: Arm B: Faricimab, 1.5 mg Q4W; Participants will receive faricimab 1.5 mg IVT Q4W up to Week 32 (total 9 injections). The final study visit will take place at Week 36.	Drug: Faricimab; Faricimab will be administered as per the regimen specified in the individual arm.; Other Names: RO6867461; RG7716
Experimental: Arm C: Faricimab, 6 mg Q4W; Participants will receive faricimab 6 mg IVT Q4W up to Week 32 (9 injections). The final study visit will take place at Week 36.	Drug: Faricimab; Faricimab will be administered as per the regimen specified in the individual arm.; Other Names: RO6867461; RG7716
Experimental: Arm D: Faricimab, 6 mg Every 4-8 weeks; Participants will receive faricimab, 6 mg IVT Q4W up to Week 12 (4 injections), followed by 6 mg IVT every 8 weeks up to Week 28 (2 injections). On Weeks 16, 24, and 32, participants received the sham procedure in order to maintain masking. The final study visit will take place at Week 36.	Drug: Faricimab; Faricimab will be administered as per the regimen specified in the individual arm.; Other Names: RO6867461; RG7716; Drug: Sham Procedure; The sham is a procedure that mimics an intravitreal injection, but involves the blunt end of an empty syringe (without a needle) being pressed against the anesthetized eye. It will be administered to participants in treatment arm D at applicable visits to maintain masking.
Experimental: Arm E: Ranibizumab 0.5 mg + Faricimab 6 mg Q4W; Participants will receive ranibizumab, 0.5 mg IVT Q4W up to Week 8 (3 injections), followed by faricimab, 6 mg IVT Q4W up to Week 32 (6 injections). The final study visit will take place at Week 36.	Drug: Ranibizumab; Ranibizumab will be administered as per the regimen specified in the individual arm.; Other Names: Lucentis; Drug: Faricimab; Faricimab will be administered as per the regimen specified in the individual arm.; 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 36, 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 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 Mixed Effects Model for Repeated Measurements (MMRM). Missing data were implicitly imputed by the MMRM, assuming a missing-at-random mechanism.	Baseline, Week 36
Mean Change From Week 12 in BCVA Letter Score at Week 36, in Anti-VEGF Incomplete Responders	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 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 Mixed Effects Model for Repeated Measurements (MMRM). Missing data were implicitly imputed by the MMRM, assuming a missing-at-random mechanism.	Weeks 12 and 36

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Gaining Greater Than or Equal to (≥) 15 Letters From Baseline in BCVA Letter Score at Week 36, 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 36
Percentage of Participants Gaining ≥15 Letters From Week 12 in BCVA Letter Score at Week 36, in Anti-VEGF Incomplete Responders	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. Missing values were not imputed; it was assumed that the data were missing at random.	Weeks 12 and 36
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better at Week 36, 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 36
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better at Week 36, in Anti-VEGF Incomplete Responders	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. Missing values were not imputed; it was assumed that the data were missing at random.	Week 36
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse at Week 36, 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 36
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse at Week 36, in Anti-VEGF Incomplete Responders	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. Missing values were not imputed; it was assumed that the data were missing at random.	Week 36
Mean Change From Baseline in Foveal Center Point Thickness at Week 36, as Measured by Spectral Domain Optical Coherence Tomography (SD-OCT), 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). Anatomic outcome measures were based on results from a central reading center. This analysis used a Mixed Effects Model for Repeated Measurements (MMRM). Missing data were implicitly imputed by the MMRM, assuming a missing-at-random mechanism.	Baseline, Week 36
Mean Change From Week 12 in Foveal Center Point Thickness at Week 36, as Measured by SD-OCT, in Anti-VEGF Incomplete Responders	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). Anatomic outcome measures were based on results from a central reading center. This analysis used a Mixed Effects Model for Repeated Measurements (MMRM). Missing data were implicitly imputed by the MMRM, assuming a missing-at-random mechanism.	Weeks 12 and 36
Mean Change From Baseline in Central Subfield Thickness at Week 36, as Measured by SD-OCT, 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 spectral domain optical coherence tomography (SD-OCT). Anatomic outcome measures were based on results from a central reading center. This analysis used a Mixed Effects Model for Repeated Measurements (MMRM). Missing data were implicitly imputed by the MMRM, assuming a missing-at-random mechanism.	Baseline, Week 36
Mean Change From Week 12 in Central Subfield Thickness at Week 36, as Measured by SD-OCT in Anti-VEGF Incomplete Responders	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 spectral domain optical coherence tomography (SD-OCT). Anatomic outcome measures were based on results from a central reading center. This analysis used a Mixed Effects Model for Repeated Measurements (MMRM). Missing data were implicitly imputed by the MMRM, assuming a missing-at-random mechanism.	Weeks 12 and 36
Number of Participants With Resolution of Dry Retina at Week 36, Defined as Absence of Cysts, Intraretinal Fluid, Pigment Epithelial Detachment, or Subretinal Fluid as Measured by SD-OCT, in Treatment-Naive Participants	The presence of cysts, intraretinal fluid, pigment epithelial detachment, or subretinal fluid, as per the study's dry retina definition, were evaluated as individual dry retina outcomes. Cysts were defined as the presence of cystoid space (fluid) in the retina. Intraretinal fluid was defined as the presence of fluid within the retina. Pigment epithelial detachment was defined as the presence of a detachment of the pigment epithelium from the Bruch's membrane. Subretinal fluid was defined as the presence of fluid between the retina and the retinal pigment epithelium. All parameters were measured using spectral domain optical coherence tomography (SD-OCT). Anatomic outcome measures were based on results from a central reading center.	Baseline, Week 36
Number of Participants With Resolution of Dry Retina at Week 36, Defined as Absence of Cysts, Intraretinal Fluid, Pigment Epithelial Detachment, or Subretinal Fluid as Measured by SD-OCT, in Anti-VEGF Incomplete Responders	The presence of cysts, intraretinal fluid, pigment epithelial detachment, or subretinal fluid, as per the study's dry retina definition, were evaluated as individual dry retina outcomes. Cysts were defined as the presence of cystoid space (fluid) in the retina. Intraretinal fluid was defined as the presence of fluid within the retina. Pigment epithelial detachment was defined as the presence of a detachment of the pigment epithelium from the Bruch's membrane. Subretinal fluid was defined as the presence of fluid between the retina and the retinal pigment epithelium. All parameters were measured using spectral domain optical coherence tomography (SD-OCT). Anatomic outcome measures were based on results from a central reading center.	Weeks 12 and 36
Mean Change From Baseline in Total Area of Choroidal Neovascularization (CNV) at Week 36, as Measured by Fundus Fluorescein Angiography (FFA), in Treatment-Naive Participants	The total area of choroidal neovascularization (CNV) was evaluated by a central reading center using fundus fluorescein angiography (FFA). This analysis used a Mixed Effects Model for Repeated Measurements (MMRM). Missing data were implicitly imputed by the MMRM, assuming a missing-at-random mechanism.	Baseline, Week 36
Mean Change From Week 12 in Total Area of Choroidal Neovascularization (CNV) at Week 36, as Measured by FFA, in Anti-VEGF Incomplete Responders	The total area of choroidal neovascularization (CNV) was evaluated by a central reading center using fundus fluorescein angiography (FFA).	Weeks 12 and 36
Mean Change From Baseline in Total Area of Choroidal Neovascularization (CNV) Component at Week 36, as Measured by FFA, in Treatment-Naive Participants	The total area of choroidal neovascularization (CNV) component (i.e., total area of CNV membrane) was evaluated by a central reading center using fundus fluorescein angiography (FFA). This analysis used a Mixed Effects Model for Repeated Measurements (MMRM). Missing data were implicitly imputed by the MMRM, assuming a missing-at-random mechanism.	Baseline, Week 36
Mean Change From Week 12 in Total Area of Choroidal Neovascularization (CNV) Component at Week 36, as Measured by FFA, in Anti-VEGF Incomplete Responders	The total area of choroidal neovascularization (CNV) component (i.e., total area of CNV membrane) was evaluated by a central reading center using fundus fluorescein angiography (FFA).	Weeks 12 and 36
Mean Change From Baseline in Total Area of Leakage at Week 36, as Measured by FFA, in Treatment-Naive Participants	The total area of leakage was evaluated by a central reading center using fundus fluorescein angiography (FFA). This analysis used a Mixed Effects Model for Repeated Measurements (MMRM). Missing data were implicitly imputed by the MMRM, assuming a missing-at-random mechanism.	Baseline, Week 36
Mean Change From Week 12 in Total Area of Leakage at Week 36, as Measured by FFA, in Anti-VEGF Incomplete Responders	The total area of leakage was evaluated by a central reading center using fundus fluorescein angiography (FFA).	Weeks 12 and 36
Safety Summary of the Overall Number of Participants With at Least One Adverse Event by Event Type, in All Participants	This safety summary reports the number and percentage of participants who experienced at least one adverse event (AE) during the study. 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 (withdrawal) of treatment with study drug, and AEs with fatal outcome. The investigator independently assessed the seriousness and severity for each AE. Severity was graded 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. Severity and seriousness are not synonymous; regardless of severity, some AEs may have also met seriousness criteria.	From Baseline until 28 days after the last dose of study treatment (up to 36 weeks)
Number of Participants With at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye 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 until 28 days after the last dose of study treatment (up to 36 weeks)
Number of Participants With at Least One Systemic Adverse Event 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 until 28 days after the last dose of study treatment (up to 36 weeks)
Number of Participants With Abnormal Systolic Blood Pressure, in All Participants	Abnormal systolic blood pressure (supine) was defined as any value outside of the standard reference range, from <70 (low) to >140 (high) millimetres of mercury (mmHg). 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.	Assessed at each study visit from Baseline until 28 days after the last dose of study treatment (up to 36 weeks)
Number of Participants With Abnormal Diastolic Blood Pressure, in All Participants	Abnormal diastolic blood pressure (supine) was defined as any value outside of the standard reference range, from <40 (low) to >90 (high) millimetres of mercury (mmHg). 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.	Assessed at each study visit from Baseline until 28 days after the last dose of study treatment (up to 36 weeks)
Number of Participants With Abnormal Heart Rate, 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.	Assessed at each study visit from Baseline until 28 days after the last dose of study treatment (up to 36 weeks)
Number of Participants With Abnormal Body Temperature, 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.	Assessed at each study visit from Baseline until 28 days after the last dose of study treatment (up to 36 weeks)
Number of Participants With Marked Laboratory Abnormalities in Hematology and Coagulation Tests, in All Participants	Clinical laboratory tests for hematology and 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. Abs. = absolute count; Corp. = corpuscular; Ery. = erythrocyte; INR = International Normalized Ratio	Predose at Baseline, Weeks 12 and 36, 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. GGT = gamma-glutamyltransferase; SGOT/AST = serum glutamic oxaloacetic transaminase / aspartate aminotransferase; SGPT/ALT = serum glutamic pyruvic transaminase / alanine aminotransferase	Predose at Baseline, Weeks 12 and 36, and at Early Termination and Unscheduled Visits (up to 36 weeks)
Mean Change From Baseline in Intraocular Pressure in the Study Eye Over Time, in All Participants	Intraocular pressure is the fluid pressure inside the eye. The method used to measure intraocular pressure (e.g., Goldmann tonometry) for each participant was to be applied consistently by the investigator throughout the study. On the day of dosing, intraocular pressure was monitored at 30 minutes post-treatment administration, and if intraocular pressure was ≥30 mmHg in the study eye, it was reassessed at 1 hour post-treatment administration.	Baseline, 0.5 hours postdose on Day 1, predose and 0.5 hours postdose at Weeks 4, 8, 12, 16, 20, 24, 28, and 32, and at Weeks 1, 13, and 36
Change From Baseline in the Number of Participants With Anti-Drug Antibodies to Faricimab at Any Post-Baseline Timepoint	Blood samples were obtained for measurement of anti-faricimab antibodies by a validated enzyme-linked immunosorbent assay (ELISA).	Baseline, Predose (0 hour) on Days 1, 28, 84, 112, 168, and 252 or early termination (up to 36 weeks)
Mean Plasma Concentration of Faricimab Over Time, in All Participants	Plasma concentrations of faricimab were measured by a specific validated enzyme-linked immunoabsorbent assay (ELISA) only from samples of participants randomized to receive faricimab. Baseline was defined as the last non-missing predose assessment. The lower limit of quantification (LLOQ) for the faricimab assay was 0.800 nanograms per millilitre (ng/mL). Values below the limit of quantification were imputed as LLOQ divided by 2.	Predose (on days when treatment was administered) at Baseline and Weeks 4, 12, 13, 16, 24, and 36
Mean Change From Baseline in Free Vascular Endothelial Growth Factor-A (VEGF-A) Plasma Concentrations Over Time, in All 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, Weeks 4, 12, 13, 16, 24, and 36
Mean Change From Baseline in Total Angiopoietin-2 (Ang-2) Plasma Concentrations Over Time, in All 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, Weeks 4, 12, 13, 16, 24, and 36
Mean Change From Baseline in Free Angiopoietin-2 (Ang-2) Plasma Concentrations Over Time, in All 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, Weeks 4, 12, 13, 16, 24, and 36

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Maunz A, Benmansour F, Li Y, Albrecht T, Zhang YP, Arcadu F, Zheng Y, Madhusudhan S, Sahni J. Accuracy of a Machine-Learning Algorithm for Detecting and Classifying Choroidal Neovascularization on Spectral-Domain Optical Coherence Tomography. J Pers Med. 2021 Jun 8;11(6):524. doi: 10.3390/jpm11060524.
• Sahni J, Dugel PU, Patel SS, Chittum ME, Berger B, Del Valle Rubido M, Sadikhov S, Szczesny P, Schwab D, Nogoceke E, Weikert R, Fauser S. Safety and Efficacy of Different Doses and Regimens of Faricimab vs Ranibizumab in Neovascular Age-Related Macular Degeneration: The AVENUE Phase 2 Randomized Clinical Trial. JAMA Ophthalmol. 2020 Sep 1;138(9):955-963. doi: 10.1001/jamaophthalmol.2020.2685.

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 2015
• Primary Completion (Actual): September 26, 2017
• Study Completion (Actual): September 26, 2017

Study Registration Dates

• First Submitted: June 12, 2015
• First Submitted That Met QC Criteria: June 24, 2015
• First Posted (Estimate): June 30, 2015

Study Record Updates

• Last Update Posted (Actual): November 12, 2020
• Last Update Submitted That Met QC Criteria: October 20, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Eye Diseases; Retinal Degeneration; Retinal Diseases; Uveal Diseases; Choroid Diseases; Metaplasia; Macular Degeneration; Choroidal Neovascularization; Neovascularization, Pathologic; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Ranibizumab
• Other Study ID Numbers: BP29647

Drug and device information, study documents

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