Clinical trial NCT02484690: A Proof-of-Concept Study of Faricimab (RO6867461) in Participants With Choroidal Neovascularization (CNV) Secondary to Age-Related Macular Degeneration (AMD)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Choroidal Neovascularization
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2015-06-30
Enrollment: 273
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Mean Change From Baseline in BCVA Letter Score at Week 36, in Treatment-Naive Participants
timeFrame: Baseline, Week 36
measure: Mean Change From Week 12 in BCVA Letter Score at Week 36, in Anti-VEGF Incomplete Responders
timeFrame: Weeks 12 and 36
Secondary outcomes:
measure: Percentage of Participants Gaining Greater Than or Equal to (≥) 15 Letters From Baseline in BCVA Letter Score at Week 36, in Treatment-Naive Participants
timeFrame: Baseline, Week 36
measure: Percentage of Participants Gaining ≥15 Letters From Week 12 in BCVA Letter Score at Week 36, in Anti-VEGF Incomplete Responders
timeFrame: Weeks 12 and 36
measure: Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better at Week 36, in Treatment-Naive Participants
timeFrame: Week 36
measure: Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better at Week 36, in Anti-VEGF Incomplete Responders
timeFrame: Week 36
measure: Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse at Week 36, in Treatment-Naive Participants
timeFrame: Week 36
measure: Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse at Week 36, in Anti-VEGF Incomplete Responders
timeFrame: Week 36
measure: 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
timeFrame: Baseline, Week 36
measure: Mean Change From Week 12 in Foveal Center Point Thickness at Week 36, as Measured by SD-OCT, in Anti-VEGF Incomplete Responders
timeFrame: Weeks 12 and 36
measure: Mean Change From Baseline in Central Subfield Thickness at Week 36, as Measured by SD-OCT, in Treatment-Naive Participants
timeFrame: Baseline, Week 36
measure: Mean Change From Week 12 in Central Subfield Thickness at Week 36, as Measured by SD-OCT in Anti-VEGF Incomplete Responders
timeFrame: Weeks 12 and 36
measure: 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
timeFrame: Baseline, Week 36
measure: 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
timeFrame: Weeks 12 and 36
measure: 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
timeFrame: Baseline, Week 36
measure: Mean Change From Week 12 in Total Area of Choroidal Neovascularization (CNV) at Week 36, as Measured by FFA, in Anti-VEGF Incomplete Responders
timeFrame: Weeks 12 and 36
measure: Mean Change From Baseline in Total Area of Choroidal Neovascularization (CNV) Component at Week 36, as Measured by FFA, in Treatment-Naive Participants
timeFrame: Baseline, Week 36
measure: 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
timeFrame: Weeks 12 and 36
measure: Mean Change From Baseline in Total Area of Leakage at Week 36, as Measured by FFA, in Treatment-Naive Participants
timeFrame: Baseline, Week 36
measure: Mean Change From Week 12 in Total Area of Leakage at Week 36, as Measured by FFA, in Anti-VEGF Incomplete Responders
timeFrame: Weeks 12 and 36
measure: Safety Summary of the Overall Number of Participants With at Least One Adverse Event by Event Type, in All Participants
timeFrame: From Baseline until 28 days after the last dose of study treatment (up to 36 weeks)
measure: Number of Participants With at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye by Highest Intensity, in All Participants
timeFrame: From Baseline until 28 days after the last dose of study treatment (up to 36 weeks)
measure: Number of Participants With at Least One Systemic Adverse Event by Highest Intensity, in All Participants
timeFrame: From Baseline until 28 days after the last dose of study treatment (up to 36 weeks)
measure: Number of Participants With Abnormal Systolic Blood Pressure, in All Participants
timeFrame: Assessed at each study visit from Baseline until 28 days after the last dose of study treatment (up to 36 weeks)
measure: Number of Participants With Abnormal Diastolic Blood Pressure, in All Participants
timeFrame: Assessed at each study visit from Baseline until 28 days after the last dose of study treatment (up to 36 weeks)
measure: Number of Participants With Abnormal Heart Rate, in All Participants
timeFrame: Assessed at each study visit from Baseline until 28 days after the last dose of study treatment (up to 36 weeks)
measure: Number of Participants With Abnormal Body Temperature, in All Participants
timeFrame: Assessed at each study visit from Baseline until 28 days after the last dose of study treatment (up to 36 weeks)
measure: Number of Participants With Marked Laboratory Abnormalities in Hematology and Coagulation Tests, in All Participants
timeFrame: Predose at Baseline, Weeks 12 and 36, and at Early Termination and Unscheduled Visits (up to 36 weeks)
measure: Number of Participants With Marked Laboratory Abnormalities in Blood Chemistry Tests, in All Participants
timeFrame: Predose at Baseline, Weeks 12 and 36, and at Early Termination and Unscheduled Visits (up to 36 weeks)
measure: Mean Change From Baseline in Intraocular Pressure in the Study Eye Over Time, in All Participants
timeFrame: 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
measure: Change From Baseline in the Number of Participants With Anti-Drug Antibodies to Faricimab at Any Post-Baseline Timepoint
timeFrame: Baseline, Predose (0 hour) on Days 1, 28, 84, 112, 168, and 252 or early termination (up to 36 weeks)
measure: Mean Plasma Concentration of Faricimab Over Time, in All Participants
timeFrame: Predose (on days when treatment was administered) at Baseline and Weeks 4, 12, 13, 16, 24, and 36
measure: Mean Change From Baseline in Free Vascular Endothelial Growth Factor-A (VEGF-A) Plasma Concentrations Over Time, in All Participants
timeFrame: Baseline, Weeks 4, 12, 13, 16, 24, and 36
measure: Mean Change From Baseline in Total Angiopoietin-2 (Ang-2) Plasma Concentrations Over Time, in All Participants
timeFrame: Baseline, Weeks 4, 12, 13, 16, 24, and 36
measure: Mean Change From Baseline in Free Angiopoietin-2 (Ang-2) Plasma Concentrations Over Time, in All Participants
timeFrame: Baseline, Weeks 4, 12, 13, 16, 24, and 36
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Associated Retina Consultants
state: Arizona
city: Phoenix
country: United States
facility: Retinal Consultants of Arizona
state: Arizona
city: Bakersfield
country: United States
facility: California Retina Consultants
state: California
city: Beverly Hills
country: United States
facility: Retina-Vitreous Associates Medical Group
state: California
city: Encino
country: United States
facility: The Retina Partners
state: California
city: Poway
country: United States
facility: Retina Consultants, San Diego
state: California
city: Santa Ana
country: United States
facility: Orange County Retina Med Group
state: California
city: Walnut Creek
country: United States
facility: Bay Area Retina Associates
state: California
city: Whittier
country: United States
facility: American Institute of Research
state: California
city: Colorado Springs
country: United States
facility: Retina Consultants of Southern
state: Colorado
city: Golden
country: United States
facility: Colorado Retina Associates, PC
state: Colorado
city: Hamden
country: United States
facility: New England Retina Associates
state: Connecticut
city: Fort Myers
country: United States
facility: Retina Health Center
state: Florida
city: Fort Myers
country: United States
facility: National Ophthalmic Research Institute
state: Florida
city: Melbourne
country: United States
facility: Florida Eye Associates
state: Florida
city: Orlando
country: United States
facility: Central Florida Retina
state: Florida
city: Palm Beach Gardens
country: United States
facility: Retina Care Specialists
state: Florida
city: Saint Petersburg
country: United States
facility: Retina Vitreous Assoc of FL
state: Florida
city: Tallahassee
country: United States
facility: Southern Vitreoretinal Assoc
state: Florida
city: Augusta
country: United States
facility: Southeast Retina Center
state: Georgia
city: Marietta
country: United States
facility: Georgia Retina PC
state: Georgia
city: Indianapolis
country: United States
facility: Midwest Eye Institute Northside
state: Indiana
city: Paducah
country: United States
facility: Paducah Retinal Center
state: Kentucky
city: Chevy Chase
country: United States
facility: Retina Group of Washington
state: Maryland
city: Towson
country: United States
facility: National Retina Institute
state: Maryland
city: Worcester
country: United States
facility: Vitreo-Retinal Associates, PC
state: Massachusetts
city: Edina
country: United States
facility: Vitreoretinal Surgery
state: Minnesota
city: Toms River
country: United States
facility: Retina Associates of NJ
state: New Jersey
city: Albuquerque
country: United States
facility: Eye Associates of New Mexico
state: New Mexico
city: Great Neck
country: United States
facility: Long Is. Vitreoretinal Consult
state: New York
city: Lynbrook
country: United States
facility: Opthalmic Consultants of LI
state: New York
city: Rochester
country: United States
facility: Retina Assoc of Western NY
state: New York
city: Slingerlands
country: United States
facility: The Retina Consultants
state: New York
city: Asheville
country: United States
facility: Western Carolina Retinal Associate PA
state: North Carolina
city: Charlotte
country: United States
facility: Char Eye Ear &Throat Assoc
state: North Carolina
city: Columbus
country: United States
facility: OSU Eye Physicians & Surgeons
state: Ohio
city: Eugene
country: United States
facility: Oregon Retina, LLP
state: Oregon
city: Medford
country: United States
facility: Oregon Retina institute
state: Oregon
city: Portland
country: United States
facility: Retina Northwest
state: Oregon
city: Philadelphia
country: United States
facility: Mid Atlantic Retina
state: Pennsylvania
city: West Columbia
country: United States
facility: Palmetto Retina Center
state: South Carolina
city: Chattanooga
country: United States
facility: Southeastern Retina Associates Chattanooga
state: Tennessee
city: Germantown
country: United States
facility: Charles Retina Institute
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Retina PC.
state: Tennessee
city: Abilene
country: United States
facility: W Texas Retina Consultants PA
state: Texas
city: Austin
country: United States
facility: Austin Retina Associates
state: Texas
city: Austin
country: United States
facility: Retina Research Center
state: Texas
city: Houston
country: United States
facility: Retina Consultants of Houston
state: Texas
city: Willow Park
country: United States
facility: Strategic Clinical Research Group, LLC
state: Texas
city: Salt Lake City
country: United States
facility: Retina Associates of Utah
state: Utah
city: Charlottesville
country: United States
facility: Univ of Virginia Ophthalmology
state: Virginia
city: Spokane
country: United States
facility: Spokane Eye Clinical Research
state: Washington
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.