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
1 other identifier
interventional
273
1 country
52
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Aug 2015
52 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 12, 2015
CompletedFirst Posted
Study publicly available on registry
June 30, 2015
CompletedStudy Start
First participant enrolled
August 11, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 26, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
September 26, 2017
CompletedResults Posted
Study results publicly available
October 9, 2020
CompletedNovember 12, 2020
October 1, 2020
2.1 years
June 12, 2015
September 16, 2020
October 20, 2020
Conditions
Outcome Measures
Primary Outcomes (2)
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 Outcomes (33)
Percentage of Participants Gaining Greater Than or Equal to (≥) 15 Letters From Baseline in BCVA Letter Score at Week 36, in Treatment-Naive Participants
Baseline, Week 36
Percentage of Participants Gaining ≥15 Letters From Week 12 in BCVA Letter Score at Week 36, in Anti-VEGF Incomplete Responders
Weeks 12 and 36
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better at Week 36, in Treatment-Naive Participants
Week 36
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better at Week 36, in Anti-VEGF Incomplete Responders
Week 36
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse at Week 36, in Treatment-Naive Participants
Week 36
- +28 more secondary outcomes
Study Arms (5)
Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W)
ACTIVE COMPARATORParticipants 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.
Arm B: Faricimab, 1.5 mg Q4W
EXPERIMENTALParticipants 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.
Arm C: Faricimab, 6 mg Q4W
EXPERIMENTALParticipants will receive faricimab 6 mg IVT Q4W up to Week 32 (9 injections). The final study visit will take place at Week 36.
Arm D: Faricimab, 6 mg Every 4-8 weeks
EXPERIMENTALParticipants 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.
Arm E: Ranibizumab 0.5 mg + Faricimab 6 mg Q4W
EXPERIMENTALParticipants 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.
Interventions
Faricimab will be administered as per the regimen specified in the individual arm.
Ranibizumab will be administered as per the regimen specified in the individual arm.
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.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (52)
Associated Retina Consultants
Phoenix, Arizona, 85020, United States
Retinal Consultants of Arizona
Phoenix, Arizona, 85053, United States
California Retina Consultants
Bakersfield, California, 93309, United States
Retina-Vitreous Associates Medical Group
Beverly Hills, California, 90211, United States
The Retina Partners
Encino, California, 91436, United States
Retina Consultants, San Diego
Poway, California, 92064, United States
Orange County Retina Med Group
Santa Ana, California, 92705, United States
Bay Area Retina Associates
Walnut Creek, California, 94598, United States
American Institute of Research
Whittier, California, 90603, United States
Retina Consultants of Southern
Colorado Springs, Colorado, 80909, United States
Colorado Retina Associates, PC
Golden, Colorado, 80401, United States
New England Retina Associates
Hamden, Connecticut, 06518, United States
Retina Health Center
Fort Myers, Florida, 33907, United States
National Ophthalmic Research Institute
Fort Myers, Florida, 33912, United States
Florida Eye Associates
Melbourne, Florida, 32901, United States
Central Florida Retina
Orlando, Florida, 32806, United States
Retina Care Specialists
Palm Beach Gardens, Florida, 33410, United States
Retina Vitreous Assoc of FL
St. Petersburg, Florida, 33711, United States
Southern Vitreoretinal Assoc
Tallahassee, Florida, 32308, United States
Southeast Retina Center
Augusta, Georgia, 30909, United States
Georgia Retina PC
Marietta, Georgia, 30060, United States
Midwest Eye Institute Northside
Indianapolis, Indiana, 46290, United States
Paducah Retinal Center
Paducah, Kentucky, 42001, United States
Retina Group of Washington
Chevy Chase, Maryland, 20815, United States
National Retina Institute
Towson, Maryland, 21204, United States
Vitreo-Retinal Associates, PC
Worcester, Massachusetts, 01605, United States
Vitreoretinal Surgery
Edina, Minnesota, 55435, United States
Retina Associates of NJ
Toms River, New Jersey, 08755, United States
Eye Associates of New Mexico
Albuquerque, New Mexico, 87102, United States
Long Is. Vitreoretinal Consult
Great Neck, New York, 11021, United States
Opthalmic Consultants of LI
Lynbrook, New York, 11563, United States
Retina Assoc of Western NY
Rochester, New York, 14620, United States
The Retina Consultants
Slingerlands, New York, 12159, United States
Western Carolina Retinal Associate PA
Asheville, North Carolina, 28803, United States
Char Eye Ear &Throat Assoc
Charlotte, North Carolina, 28210, United States
OSU Eye Physicians & Surgeons
Columbus, Ohio, 43212, United States
Oregon Retina, LLP
Eugene, Oregon, 97401, United States
Oregon Retina institute
Medford, Oregon, 97504, United States
Retina Northwest
Portland, Oregon, 97221, United States
Mid Atlantic Retina
Philadelphia, Pennsylvania, 19107, United States
Palmetto Retina Center
West Columbia, South Carolina, 29169, United States
Southeastern Retina Associates Chattanooga
Chattanooga, Tennessee, 37421, United States
Charles Retina Institute
Germantown, Tennessee, 38138, United States
Tennessee Retina PC.
Nashville, Tennessee, 37203, United States
W Texas Retina Consultants PA
Abilene, Texas, 79606, United States
Austin Retina Associates
Austin, Texas, 78705, United States
Retina Research Center
Austin, Texas, 78705, United States
Retina Consultants of Houston
Houston, Texas, 77030, United States
Strategic Clinical Research Group, LLC
Willow Park, Texas, 76087, United States
Retina Associates of Utah
Salt Lake City, Utah, 84107, United States
Univ of Virginia Ophthalmology
Charlottesville, Virginia, 22903, United States
Spokane Eye Clinical Research
Spokane, Washington, 99204, United States
Related Publications (4)
Kikuchi Y, Kawczynski MG, Anegondi N, Neubert A, Dai J, Ferrara D, Quezada-Ruiz C. Machine Learning to Predict Faricimab Treatment Outcome in Neovascular Age-Related Macular Degeneration. Ophthalmol Sci. 2023 Aug 18;4(2):100385. doi: 10.1016/j.xops.2023.100385. eCollection 2024 Mar-Apr.
PMID: 37868796DERIVEDYu S, Bachmeier I, Hernandez-Sanchez J, Garcia Armendariz B, Ebneter A, Pauleikhoff D, Chakravarthy U, Fauser S. Hyperreflective Material Boundary Remodeling in Neovascular Age-Related Macular Degeneration: A Post Hoc Analysis of the AVENUE Trial. Ophthalmol Retina. 2023 Nov;7(11):990-998. doi: 10.1016/j.oret.2023.06.024. Epub 2023 Jul 6.
PMID: 37422192DERIVEDMaunz 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.
PMID: 34201045DERIVEDSahni 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.
PMID: 32729888DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
The small number of participants per cohort only allows detection of large differences in outcomes; not designed to show noninferiority of faricimab relative to ranibizumab. The short duration further limits information on long-term visual potential.
Results Point of Contact
- Title
- Medical Communications
- Organization
- Hoffmann-La Roche
Study Officials
- STUDY DIRECTOR
Clinical Trials
Hoffmann-La Roche
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 12, 2015
First Posted
June 30, 2015
Study Start
August 11, 2015
Primary Completion
September 26, 2017
Study Completion
September 26, 2017
Last Updated
November 12, 2020
Results First Posted
October 9, 2020
Record last verified: 2020-10