Neovascular Age-related Macular Degeneration
Conditions
Brief summary
This main long-term extension study is designed to evaluate the long-term safety and tolerability of faricimab 6 milligrams (mg) administered by intravitreal injection at a personalized treatment interval (PTI) to participants with neovascular age-related macular degeneration (nAMD) who enrolled in and completed one of the Phase III studies: GR40306 (NCT03823287) or GR40844 (NCT03823300), also referred to as the parent studies. Eligible patients who consent to participate in this main study will be enrolled upon completion of the end-of-study visit in the parent study. Additionally, there is a substudy that is being conducted. The aim of this substudy is to evaluate the impact of intravitreal faricimab on the health of the corneal endothelial cells in the study eyes of patients with nAMD to fulfill a U.S. Food and Drug Administration (FDA) post-marketing requirement. The fellow eyes of the same enrolled participants in the substudy will serve as the controls.
Interventions
DRUGFaricimab
Faricimab 6 mg will be administered by intravitreal (IVT) injection into the study eye according to the personalized treatment interval (PTI) dosing regimen for the duration of the study.
OTHERSham Procedure
The sham is a procedure that mimics an IVT injection and involves the blunt end of an empty syringe (without a needle) being pressed against the anesthetized eye. The sham procedure will be administered to participants as appropriate during the first 12 weeks of this study in order to maintain the masking of the initial faricimab PTI.
DRUGAnti-VEGF Therapy
At the discretion of the principal investigator, participants were allowed to have their fellow (non-study) eye treated with the standard of care anti-VEGF therapy (if needed) according to region-specific anti-VEGF prescribing information for the recommended dose and frequency of treatment.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
The first 12 weeks of the main study will be a masked period (to transition from the multi-arm parent studies) during which participants may receive either faricimab or sham injection. Participants and physicians will be masked only to the faricimab treatment interval. After the Week 12 treatment procedure, this study will follow an open-label design. The BCVA examiner will remain masked for the duration of the main long-term extension study.
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
for the Main Study: * Previous enrollment in and completion of Study GR40306 (NCT03823287) or Study GR40844 (NCT03823300), without study or study drug discontinuation * For women of childbearing potential: agreement to remain abstinent or use contraception, and agreement to refrain from donating eggs. Women must remain abstinent or use contraceptive methods with a failure rate of \< 1% per year during the treatment period and for 3 months after the final dose of faricimab. Women must refrain from donating eggs during the same period. Inclusion Criteria for the Substudy: * In addition to all inclusion criteria specified in the main Study GR42691, participants in the Substudy must meet the following criteria: * Sign an informed consent form for the Substudy * Must be able to participate for at least 48 weeks in the Substudy and have at least the first visit while enrolled in the main Study GR42691 * A difference of \<10% in corneal endothelial cell density at screening between the two eyes as measured by specular microscopy and determined by the independent reading center
Exclusion criteria
for the Main Study: * Pregnant or breastfeeding, or intending to become pregnant during the study or within 3 months after the final dose of faricimab * Presence of other ocular diseases that give reasonable suspicion of a disease or condition that contraindicates the use of faricimab, that might affect interpretation of the results of the study or that renders the patient at high risk for treatment complications * Presence of other diseases, metabolic dysfunction, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of faricimab and that might affect interpretation of the results of the study or that renders the patient at high risk of treatment complications * History of a severe allergic reaction or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of the faricimab injections, study-related procedure preparations, dilating drops, or any of the anesthetic and antimicrobial preparations used by a patient during the study * Requirement for continuous use of any medications or treatments indicated as prohibited therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale | From the date of first administration of faricimab through 28 days after the end of study (up to 2 years) | This is an analysis of participants with at least one ocular adverse event (AE) that occurred in the study eye. Investigators sought information on AEs at each contact with the participants. All AEs were recorded and the investigator made an assessment of the seriousness, severity (e.g., mild, moderate, or severe intensity), and causality for each AE. AEs of special interest (AESI) included the following: Sight-threatening AEs that cause a drop in visual acuity (VA) score ≥30 letters lasting more than 1 hour, are associated with severe intraocular inflammation (IOI), or require surgical or medical intervention to prevent permanent loss of sight; suspected transmission of an infectious agent by the study drug; and, cases of potential drug-induced liver injury that include an elevated ALT or AST in combination with either an elevated bilirubin or clinical jaundice, as defined by Hy's Law. |
| Incidence of Ocular Adverse Events in the Fellow Eye | From the date of first administration of faricimab through 28 days after the end of study (up to 2 years) | This is an analysis of participants with at least one ocular adverse event (AE) that occurred in the study eye. Investigators sought information on AEs at each contact with the participants. All AEs were recorded and the investigator made an assessment of the seriousness, severity, and causality for each AE. AEs of special interest (AESI) included the following: Sight-threatening AEs that cause a drop in visual acuity (VA) score ≥30 letters lasting more than 1 hour, are associated with severe intraocular inflammation (IOI), or require surgical or medical intervention to prevent permanent loss of sight; suspected transmission of an infectious agent by the study drug; and, cases of potential drug-induced liver injury that include an elevated ALT or AST in combination with either an elevated bilirubin or clinical jaundice, as defined by Hy's Law. |
| Incidence and Severity of Non-Ocular Adverse Events, With Severity Determined According to Adverse Event Severity Grading Scale | From the date of first administration of faricimab through 28 days after the end of study (up to 2 years) | This is an analysis of participants with at least one non-ocular (systemic) adverse event (AE). Investigators sought information on AEs at each contact with the participants. All AEs were recorded and the investigator made an assessment of the seriousness, severity (e.g., mild, moderate, or severe intensity), and causality for each AE. AEs of special interest (AESI) included the following: Sight-threatening AEs that cause a drop in visual acuity (VA) score ≥30 letters lasting more than 1 hour, are associated with severe intraocular inflammation (IOI), or require surgical or medical intervention to prevent permanent loss of sight; suspected transmission of an infectious agent by the study drug; and, cases of potential drug-induced liver injury that include an elevated ALT or AST in combination with either an elevated bilirubin or clinical jaundice, as defined by Hy's Law. |
| Substudy: Percent Change in Corneal Endothelial Cell Density From Baseline at 1 Year in the Study Eye as Compared With the Fellow Eye | Baseline and 1 year | Specular microscopy was performed for both eyes prior to application of any topical ophthalmic anesthetic, tonometry, or any other study treatment on the same day for the evaluation of corneal endothelial cell (CEC) density. The 1-year timepoint was defined as the earliest substudy visit closest to Week 52 occurring between Week 48 and Week 64. Data (from both study eye and fellow eye) collected after the fellow eye's use of prohibited therapies-such as faricimab, brolucizumab, bevacizumab, and Port Delivery System implantation-were excluded from the corneal endothelial cell analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Substudy: Percent Change in Corneal Endothelial Cell Density From Baseline at Week 24 in the Study Eye as Compared With the Fellow Eye | Baseline and Week 24 | Specular microscopy was performed for both eyes prior to application of any topical ophthalmic anesthetic, tonometry, or any other study treatment on the same day for the evaluation of corneal endothelial cell (CEC) density. The Week 24 timepoint was defined as the earliest substudy visit closest to Week 24 occurring between Week 20 and Week 28. Data (from both study eye and fellow eye) collected after the fellow eye's use of prohibited therapies-such as faricimab, brolucizumab, bevacizumab, and Port Delivery System implantation-were excluded from the corneal endothelial cell analysis. |
Countries
Argentina, Australia, Austria, Brazil, Bulgaria, Canada, Denmark, France, Germany, Hong Kong, Hungary, Israel, Italy, Japan, Mexico, Netherlands, Poland, Portugal, Russia, Singapore, South Korea, Spain, Switzerland, Taiwan, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
A total of 1036 participants were enrolled in the main study, 7 of whom were excluded from analysis, resulting in a final analysis set of 1029 participants. A subgroup of 117 also participated concurrently in the substudy. Only 1 eye for each participant was assigned as the study eye in the prior parent studies, per the eligibility criteria, to receive study intervention; that study eye remained the same in this main study and substudy. The fellow (other) eye was not assigned to an intervention.
Pre-assignment details
A total of 7 patients were not included in the analysis set prior to assignment. This was a precautionary measure following a Good Clinical Practice (GCP) non-compliance audit finding at a single clinical trial site for a different investigational product.
Participants by arm
| Arm | Count |
|---|---|
| Main Study Cohort A: Faricimab PTI (Prior Faricimab) This cohort included participants previously randomized to Arm A (faricimab up to every 16 weeks \[Q16W\]) in the parent studies \[GR40306 (NCT03823287) or GR40844 (NCT03823300)\]. In this long-term extension study, faricimab 6 mg was administered by intravitreal (IVT) injection into the study eye according to the personalized treatment interval (PTI) dosing regimen for the duration of the study. | 524 |
| Main Study Cohort B: Faricimab PTI (Prior Aflibercept) This cohort included participants previously randomized to Arm B (aflibercept 2mg Q8W) in the parent studies \[GR40306 (NCT03823287) or GR40844 (NCT03823300)\]. In this long-term extension study, faricimab 6 mg was administered by intravitreal (IVT) injection into the study eye according to the personalized treatment interval (PTI) dosing regimen for the duration of the study. | 505 |
| Substudy: Faricimab PTI Participants from the main long-term extension study who also consented to participate in this substudy received faricimab 6 mg by intravitreal (IVT) injection into the study eye according to the personalized treatment interval (PTI) dosing regimen for the duration of the study. The participant's fellow eye was not assigned to an intervention. At the discretion of the principal investigator, a participant may have had their fellow eye treated with anti-VEGF therapy licensed for ocular use if the participant was diagnosed with an ocular condition for which the selected anti-VEGF therapy was approved by the country's regulatory agency. Administration of the following therapies to the fellow eye were prohibited during the substudy: faricimab, brolucizumab, bevacizumab, and Port Delivery System implantation. | 113 |
| Total | 1,142 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Main Study | Adverse Event | 8 | 8 | 0 |
| Main Study | Death | 13 | 27 | 0 |
| Main Study | Lack of Efficacy | 1 | 1 | 0 |
| Main Study | Lost to Follow-up | 9 | 4 | 0 |
| Main Study | Physician Decision | 8 | 10 | 0 |
| Main Study | Protocol Violation | 1 | 0 | 0 |
| Main Study | Reason not specified | 3 | 3 | 0 |
| Main Study | Subject missed the safety follow-up visit | 9 | 10 | 0 |
| Main Study | Withdrawal by Subject | 19 | 27 | 0 |
| Substudy (Concurrent With Main Study) | Adverse Event | 0 | 0 | 1 |
| Substudy (Concurrent With Main Study) | Cataract Surgery | 0 | 0 | 1 |
| Substudy (Concurrent With Main Study) | Lost to Follow-up | 0 | 0 | 1 |
| Substudy (Concurrent With Main Study) | Physician Decision | 0 | 0 | 1 |
| Substudy (Concurrent With Main Study) | Prohibited Medication | 0 | 0 | 2 |
| Substudy (Concurrent With Main Study) | Withdrawal by Subject | 0 | 0 | 4 |
Baseline characteristics
| Characteristic | Main Study Cohort A: Faricimab PTI (Prior Faricimab) | Main Study Cohort B: Faricimab PTI (Prior Aflibercept) | Total | Substudy: Faricimab PTI |
|---|---|---|---|---|
| Age, Continuous Main Study | 76.4 Years STANDARD_DEVIATION 8.2 | 77.7 Years STANDARD_DEVIATION 8.8 | 77.0 Years STANDARD_DEVIATION 8.5 | — |
| Age, Continuous Substudy | — | — | 75.6 Years STANDARD_DEVIATION 8.1 | 75.6 Years STANDARD_DEVIATION 8.1 |
| Ethnicity (NIH/OMB) Main Study Hispanic or Latino | 50 Participants | 53 Participants | 103 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Main Study Not Hispanic or Latino | 463 Participants | 445 Participants | 908 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Main Study Unknown or Not Reported | 11 Participants | 7 Participants | 18 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Substudy Hispanic or Latino | 0 Participants | 0 Participants | 23 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Substudy Not Hispanic or Latino | 0 Participants | 0 Participants | 90 Participants | 90 Participants |
| Ethnicity (NIH/OMB) Substudy Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Main Study American Indian or Alaska Native | 2 Participants | 2 Participants | 4 Participants | 0 Participants |
| Race (NIH/OMB) Main Study Asian | 76 Participants | 83 Participants | 159 Participants | 0 Participants |
| Race (NIH/OMB) Main Study Black or African American | 1 Participants | 5 Participants | 6 Participants | 0 Participants |
| Race (NIH/OMB) Main Study More than one race | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Main Study Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Main Study Unknown or Not Reported | 12 Participants | 12 Participants | 24 Participants | 0 Participants |
| Race (NIH/OMB) Main Study White | 433 Participants | 402 Participants | 835 Participants | 0 Participants |
| Race (NIH/OMB) Substudy American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Substudy Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Substudy Black or African American | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Substudy More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Substudy Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Substudy Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Substudy White | 0 Participants | 0 Participants | 112 Participants | 112 Participants |
| Sex: Female, Male Main Study Female | 308 Participants | 291 Participants | 599 Participants | 0 Participants |
| Sex: Female, Male Main Study Male | 216 Participants | 214 Participants | 430 Participants | 0 Participants |
| Sex: Female, Male Substudy Female | 0 Participants | 0 Participants | 61 Participants | 61 Participants |
| Sex: Female, Male Substudy Male | 0 Participants | 0 Participants | 52 Participants | 52 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 13 / 520 | 27 / 505 | 1 / 113 |
| other Total, other adverse events | 158 / 520 | 169 / 505 | 9 / 113 |
| serious Total, serious adverse events | 125 / 520 | 156 / 505 | 14 / 113 |
Outcome results
Primary
Incidence and Severity of Non-Ocular Adverse Events, With Severity Determined According to Adverse Event Severity Grading Scale
This is an analysis of participants with at least one non-ocular (systemic) adverse event (AE). Investigators sought information on AEs at each contact with the participants. All AEs were recorded and the investigator made an assessment of the seriousness, severity (e.g., mild, moderate, or severe intensity), and causality for each AE. AEs of special interest (AESI) included the following: Sight-threatening AEs that cause a drop in visual acuity (VA) score ≥30 letters lasting more than 1 hour, are associated with severe intraocular inflammation (IOI), or require surgical or medical intervention to prevent permanent loss of sight; suspected transmission of an infectious agent by the study drug; and, cases of potential drug-induced liver injury that include an elevated ALT or AST in combination with either an elevated bilirubin or clinical jaundice, as defined by Hy's Law.
Time frame: From the date of first administration of faricimab through 28 days after the end of study (up to 2 years)
Population: Safety-Evaluable Population: all participants who enrolled in the long-term extension (LTE) study and received at least one dose of faricimab in the study eye during the LTE.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Main Study Cohort A: Faricimab PTI (Prior Faricimab) | Incidence and Severity of Non-Ocular Adverse Events, With Severity Determined According to Adverse Event Severity Grading Scale | Any Adverse Event (AE), Any Severity | 343 Participants |
| Main Study Cohort A: Faricimab PTI (Prior Faricimab) | Incidence and Severity of Non-Ocular Adverse Events, With Severity Determined According to Adverse Event Severity Grading Scale | AE by Severity: Mild | 122 Participants |
| Main Study Cohort A: Faricimab PTI (Prior Faricimab) | Incidence and Severity of Non-Ocular Adverse Events, With Severity Determined According to Adverse Event Severity Grading Scale | AE by Severity: Moderate | 138 Participants |
| Main Study Cohort A: Faricimab PTI (Prior Faricimab) | Incidence and Severity of Non-Ocular Adverse Events, With Severity Determined According to Adverse Event Severity Grading Scale | AE by Severity: Severe | 83 Participants |
| Main Study Cohort A: Faricimab PTI (Prior Faricimab) | Incidence and Severity of Non-Ocular Adverse Events, With Severity Determined According to Adverse Event Severity Grading Scale | Serious Adverse Event (SAE) | 110 Participants |
| Main Study Cohort A: Faricimab PTI (Prior Faricimab) | Incidence and Severity of Non-Ocular Adverse Events, With Severity Determined According to Adverse Event Severity Grading Scale | AE Leading to Withdrawal from Study Treatment | 3 Participants |
| Main Study Cohort A: Faricimab PTI (Prior Faricimab) | Incidence and Severity of Non-Ocular Adverse Events, With Severity Determined According to Adverse Event Severity Grading Scale | Any AE of Special Interest (AESI) | 0 Participants |
| Main Study Cohort A: Faricimab PTI (Prior Faricimab) | Incidence and Severity of Non-Ocular Adverse Events, With Severity Determined According to Adverse Event Severity Grading Scale | AESI: Elevated ALT or AST with Either Elevated Bilirubin or Clinical Jaundice | 0 Participants |
| Main Study Cohort B: Faricimab PTI (Prior Aflibercept) | Incidence and Severity of Non-Ocular Adverse Events, With Severity Determined According to Adverse Event Severity Grading Scale | AE by Severity: Moderate | 124 Participants |
| Main Study Cohort B: Faricimab PTI (Prior Aflibercept) | Incidence and Severity of Non-Ocular Adverse Events, With Severity Determined According to Adverse Event Severity Grading Scale | Any AE of Special Interest (AESI) | 0 Participants |
| Main Study Cohort B: Faricimab PTI (Prior Aflibercept) | Incidence and Severity of Non-Ocular Adverse Events, With Severity Determined According to Adverse Event Severity Grading Scale | AE by Severity: Severe | 93 Participants |
| Main Study Cohort B: Faricimab PTI (Prior Aflibercept) | Incidence and Severity of Non-Ocular Adverse Events, With Severity Determined According to Adverse Event Severity Grading Scale | Serious Adverse Event (SAE) | 127 Participants |
| Main Study Cohort B: Faricimab PTI (Prior Aflibercept) | Incidence and Severity of Non-Ocular Adverse Events, With Severity Determined According to Adverse Event Severity Grading Scale | AE Leading to Withdrawal from Study Treatment | 9 Participants |
| Main Study Cohort B: Faricimab PTI (Prior Aflibercept) | Incidence and Severity of Non-Ocular Adverse Events, With Severity Determined According to Adverse Event Severity Grading Scale | Any Adverse Event (AE), Any Severity | 337 Participants |
| Main Study Cohort B: Faricimab PTI (Prior Aflibercept) | Incidence and Severity of Non-Ocular Adverse Events, With Severity Determined According to Adverse Event Severity Grading Scale | AE by Severity: Mild | 120 Participants |
| Main Study Cohort B: Faricimab PTI (Prior Aflibercept) | Incidence and Severity of Non-Ocular Adverse Events, With Severity Determined According to Adverse Event Severity Grading Scale | AESI: Elevated ALT or AST with Either Elevated Bilirubin or Clinical Jaundice | 0 Participants |
| Substudy: Faricimab PTI | Incidence and Severity of Non-Ocular Adverse Events, With Severity Determined According to Adverse Event Severity Grading Scale | AE by Severity: Moderate | 17 Participants |
| Substudy: Faricimab PTI | Incidence and Severity of Non-Ocular Adverse Events, With Severity Determined According to Adverse Event Severity Grading Scale | AE by Severity: Mild | 15 Participants |
| Substudy: Faricimab PTI | Incidence and Severity of Non-Ocular Adverse Events, With Severity Determined According to Adverse Event Severity Grading Scale | Any Adverse Event (AE), Any Severity | 41 Participants |
| Substudy: Faricimab PTI | Incidence and Severity of Non-Ocular Adverse Events, With Severity Determined According to Adverse Event Severity Grading Scale | AE by Severity: Severe | 9 Participants |
| Substudy: Faricimab PTI | Incidence and Severity of Non-Ocular Adverse Events, With Severity Determined According to Adverse Event Severity Grading Scale | Any AE of Special Interest (AESI) | 0 Participants |
| Substudy: Faricimab PTI | Incidence and Severity of Non-Ocular Adverse Events, With Severity Determined According to Adverse Event Severity Grading Scale | AE Leading to Withdrawal from Study Treatment | 0 Participants |
| Substudy: Faricimab PTI | Incidence and Severity of Non-Ocular Adverse Events, With Severity Determined According to Adverse Event Severity Grading Scale | Serious Adverse Event (SAE) | 13 Participants |
| Substudy: Faricimab PTI | Incidence and Severity of Non-Ocular Adverse Events, With Severity Determined According to Adverse Event Severity Grading Scale | AESI: Elevated ALT or AST with Either Elevated Bilirubin or Clinical Jaundice | 0 Participants |
Primary
Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale
This is an analysis of participants with at least one ocular adverse event (AE) that occurred in the study eye. Investigators sought information on AEs at each contact with the participants. All AEs were recorded and the investigator made an assessment of the seriousness, severity (e.g., mild, moderate, or severe intensity), and causality for each AE. AEs of special interest (AESI) included the following: Sight-threatening AEs that cause a drop in visual acuity (VA) score ≥30 letters lasting more than 1 hour, are associated with severe intraocular inflammation (IOI), or require surgical or medical intervention to prevent permanent loss of sight; suspected transmission of an infectious agent by the study drug; and, cases of potential drug-induced liver injury that include an elevated ALT or AST in combination with either an elevated bilirubin or clinical jaundice, as defined by Hy's Law.
Time frame: From the date of first administration of faricimab through 28 days after the end of study (up to 2 years)
Population: Safety-Evaluable Population: all participants who enrolled in the long-term extension (LTE) study and received at least one dose of faricimab in the study eye during the LTE.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Main Study Cohort A: Faricimab PTI (Prior Faricimab) | Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale | AESI: Drop in Visual Acuity Score ≥30 Letters | 11 Participants |
| Main Study Cohort A: Faricimab PTI (Prior Faricimab) | Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale | Serious Adverse Event (SAE) | 18 Participants |
| Main Study Cohort A: Faricimab PTI (Prior Faricimab) | Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale | AEs by Severity: Moderate | 58 Participants |
| Main Study Cohort A: Faricimab PTI (Prior Faricimab) | Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale | Any AE of Special Interest (AESI) | 15 Participants |
| Main Study Cohort A: Faricimab PTI (Prior Faricimab) | Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale | AE Leading to Withdrawal from Study Treatment | 4 Participants |
| Main Study Cohort A: Faricimab PTI (Prior Faricimab) | Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale | AEs by Severity: Mild | 114 Participants |
| Main Study Cohort A: Faricimab PTI (Prior Faricimab) | Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale | Treatment-related SAE | 1 Participants |
| Main Study Cohort A: Faricimab PTI (Prior Faricimab) | Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale | Treatment-related AE | 8 Participants |
| Main Study Cohort A: Faricimab PTI (Prior Faricimab) | Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale | AESI: Associated with Severe IOI | 1 Participants |
| Main Study Cohort A: Faricimab PTI (Prior Faricimab) | Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale | AEs by Severity: Severe | 13 Participants |
| Main Study Cohort A: Faricimab PTI (Prior Faricimab) | Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale | AESI: Suspected Transmission of Infectious Agent by Study Drug | 0 Participants |
| Main Study Cohort A: Faricimab PTI (Prior Faricimab) | Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale | Any Adverse Event (AE), Any Severity | 188 Participants |
| Main Study Cohort A: Faricimab PTI (Prior Faricimab) | Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale | AEs by Severity: Missing | 3 Participants |
| Main Study Cohort A: Faricimab PTI (Prior Faricimab) | Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale | AESI: Intervention Required to Prevent Permanent Vision Loss | 3 Participants |
| Main Study Cohort B: Faricimab PTI (Prior Aflibercept) | Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale | AESI: Drop in Visual Acuity Score ≥30 Letters | 16 Participants |
| Main Study Cohort B: Faricimab PTI (Prior Aflibercept) | Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale | Any Adverse Event (AE), Any Severity | 207 Participants |
| Main Study Cohort B: Faricimab PTI (Prior Aflibercept) | Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale | AEs by Severity: Mild | 106 Participants |
| Main Study Cohort B: Faricimab PTI (Prior Aflibercept) | Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale | AEs by Severity: Moderate | 75 Participants |
| Main Study Cohort B: Faricimab PTI (Prior Aflibercept) | Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale | AEs by Severity: Severe | 23 Participants |
| Main Study Cohort B: Faricimab PTI (Prior Aflibercept) | Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale | AEs by Severity: Missing | 3 Participants |
| Main Study Cohort B: Faricimab PTI (Prior Aflibercept) | Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale | Serious Adverse Event (SAE) | 27 Participants |
| Main Study Cohort B: Faricimab PTI (Prior Aflibercept) | Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale | AE Leading to Withdrawal from Study Treatment | 5 Participants |
| Main Study Cohort B: Faricimab PTI (Prior Aflibercept) | Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale | Treatment-related AE | 12 Participants |
| Main Study Cohort B: Faricimab PTI (Prior Aflibercept) | Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale | Treatment-related SAE | 3 Participants |
| Main Study Cohort B: Faricimab PTI (Prior Aflibercept) | Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale | Any AE of Special Interest (AESI) | 21 Participants |
| Main Study Cohort B: Faricimab PTI (Prior Aflibercept) | Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale | AESI: Associated with Severe IOI | 2 Participants |
| Main Study Cohort B: Faricimab PTI (Prior Aflibercept) | Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale | AESI: Intervention Required to Prevent Permanent Vision Loss | 3 Participants |
| Main Study Cohort B: Faricimab PTI (Prior Aflibercept) | Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale | AESI: Suspected Transmission of Infectious Agent by Study Drug | 0 Participants |
| Substudy: Faricimab PTI | Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale | AESI: Intervention Required to Prevent Permanent Vision Loss | 0 Participants |
| Substudy: Faricimab PTI | Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale | Any AE of Special Interest (AESI) | 1 Participants |
| Substudy: Faricimab PTI | Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale | AEs by Severity: Missing | 0 Participants |
| Substudy: Faricimab PTI | Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale | AEs by Severity: Severe | 1 Participants |
| Substudy: Faricimab PTI | Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale | AESI: Drop in Visual Acuity Score ≥30 Letters | 1 Participants |
| Substudy: Faricimab PTI | Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale | AEs by Severity: Moderate | 4 Participants |
| Substudy: Faricimab PTI | Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale | Any Adverse Event (AE), Any Severity | 16 Participants |
| Substudy: Faricimab PTI | Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale | AESI: Associated with Severe IOI | 0 Participants |
| Substudy: Faricimab PTI | Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale | AEs by Severity: Mild | 11 Participants |
| Substudy: Faricimab PTI | Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale | Treatment-related AE | 2 Participants |
| Substudy: Faricimab PTI | Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale | AE Leading to Withdrawal from Study Treatment | 0 Participants |
| Substudy: Faricimab PTI | Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale | AESI: Suspected Transmission of Infectious Agent by Study Drug | 0 Participants |
| Substudy: Faricimab PTI | Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale | Treatment-related SAE | 1 Participants |
| Substudy: Faricimab PTI | Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale | Serious Adverse Event (SAE) | 1 Participants |
Primary
Incidence of Ocular Adverse Events in the Fellow Eye
This is an analysis of participants with at least one ocular adverse event (AE) that occurred in the study eye. Investigators sought information on AEs at each contact with the participants. All AEs were recorded and the investigator made an assessment of the seriousness, severity, and causality for each AE. AEs of special interest (AESI) included the following: Sight-threatening AEs that cause a drop in visual acuity (VA) score ≥30 letters lasting more than 1 hour, are associated with severe intraocular inflammation (IOI), or require surgical or medical intervention to prevent permanent loss of sight; suspected transmission of an infectious agent by the study drug; and, cases of potential drug-induced liver injury that include an elevated ALT or AST in combination with either an elevated bilirubin or clinical jaundice, as defined by Hy's Law.
Time frame: From the date of first administration of faricimab through 28 days after the end of study (up to 2 years)
Population: Safety-Evaluable Population: all participants who enrolled in the long-term extension (LTE) study and received at least one dose of faricimab in the study eye during the LTE.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Main Study Cohort A: Faricimab PTI (Prior Faricimab) | Incidence of Ocular Adverse Events in the Fellow Eye | Serious Adverse Event (SAE) | 4 Participants |
| Main Study Cohort A: Faricimab PTI (Prior Faricimab) | Incidence of Ocular Adverse Events in the Fellow Eye | AESI: Associated with Severe IOI | 0 Participants |
| Main Study Cohort A: Faricimab PTI (Prior Faricimab) | Incidence of Ocular Adverse Events in the Fellow Eye | AESI: Drop in Visual Acuity Score ≥30 Letters | 3 Participants |
| Main Study Cohort A: Faricimab PTI (Prior Faricimab) | Incidence of Ocular Adverse Events in the Fellow Eye | Any Adverse Event (AE), Any Severity | 157 Participants |
| Main Study Cohort A: Faricimab PTI (Prior Faricimab) | Incidence of Ocular Adverse Events in the Fellow Eye | AESI: Suspected Transmission of Infectious Agent by Study Drug | 0 Participants |
| Main Study Cohort A: Faricimab PTI (Prior Faricimab) | Incidence of Ocular Adverse Events in the Fellow Eye | AESI: Intervention Required to Prevent Permanent Vision Loss | 0 Participants |
| Main Study Cohort A: Faricimab PTI (Prior Faricimab) | Incidence of Ocular Adverse Events in the Fellow Eye | Any AE of Special Interest (AESI) | 3 Participants |
| Main Study Cohort B: Faricimab PTI (Prior Aflibercept) | Incidence of Ocular Adverse Events in the Fellow Eye | AESI: Drop in Visual Acuity Score ≥30 Letters | 8 Participants |
| Main Study Cohort B: Faricimab PTI (Prior Aflibercept) | Incidence of Ocular Adverse Events in the Fellow Eye | Any Adverse Event (AE), Any Severity | 149 Participants |
| Main Study Cohort B: Faricimab PTI (Prior Aflibercept) | Incidence of Ocular Adverse Events in the Fellow Eye | Serious Adverse Event (SAE) | 11 Participants |
| Main Study Cohort B: Faricimab PTI (Prior Aflibercept) | Incidence of Ocular Adverse Events in the Fellow Eye | Any AE of Special Interest (AESI) | 11 Participants |
| Main Study Cohort B: Faricimab PTI (Prior Aflibercept) | Incidence of Ocular Adverse Events in the Fellow Eye | AESI: Associated with Severe IOI | 0 Participants |
| Main Study Cohort B: Faricimab PTI (Prior Aflibercept) | Incidence of Ocular Adverse Events in the Fellow Eye | AESI: Intervention Required to Prevent Permanent Vision Loss | 3 Participants |
| Main Study Cohort B: Faricimab PTI (Prior Aflibercept) | Incidence of Ocular Adverse Events in the Fellow Eye | AESI: Suspected Transmission of Infectious Agent by Study Drug | 0 Participants |
| Substudy: Faricimab PTI | Incidence of Ocular Adverse Events in the Fellow Eye | AESI: Associated with Severe IOI | 0 Participants |
| Substudy: Faricimab PTI | Incidence of Ocular Adverse Events in the Fellow Eye | Serious Adverse Event (SAE) | 1 Participants |
| Substudy: Faricimab PTI | Incidence of Ocular Adverse Events in the Fellow Eye | AESI: Suspected Transmission of Infectious Agent by Study Drug | 0 Participants |
| Substudy: Faricimab PTI | Incidence of Ocular Adverse Events in the Fellow Eye | AESI: Intervention Required to Prevent Permanent Vision Loss | 1 Participants |
| Substudy: Faricimab PTI | Incidence of Ocular Adverse Events in the Fellow Eye | AESI: Drop in Visual Acuity Score ≥30 Letters | 0 Participants |
| Substudy: Faricimab PTI | Incidence of Ocular Adverse Events in the Fellow Eye | Any AE of Special Interest (AESI) | 1 Participants |
| Substudy: Faricimab PTI | Incidence of Ocular Adverse Events in the Fellow Eye | Any Adverse Event (AE), Any Severity | 17 Participants |
Primary
Substudy: Percent Change in Corneal Endothelial Cell Density From Baseline at 1 Year in the Study Eye as Compared With the Fellow Eye
Specular microscopy was performed for both eyes prior to application of any topical ophthalmic anesthetic, tonometry, or any other study treatment on the same day for the evaluation of corneal endothelial cell (CEC) density. The 1-year timepoint was defined as the earliest substudy visit closest to Week 52 occurring between Week 48 and Week 64. Data (from both study eye and fellow eye) collected after the fellow eye's use of prohibited therapies-such as faricimab, brolucizumab, bevacizumab, and Port Delivery System implantation-were excluded from the corneal endothelial cell analysis.
Time frame: Baseline and 1 year
Population: Modified Intent-to-Treat Population: All enrolled participants who received at least one injection of faricimab in the study eye during this substudy. Only participants who completed the Year 1 visit within the analysis window (Weeks 48 to 64) were included for analysis.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Main Study Cohort A: Faricimab PTI (Prior Faricimab) | Substudy: Percent Change in Corneal Endothelial Cell Density From Baseline at 1 Year in the Study Eye as Compared With the Fellow Eye | -0.51 Percent change in cell density |
| Main Study Cohort B: Faricimab PTI (Prior Aflibercept) | Substudy: Percent Change in Corneal Endothelial Cell Density From Baseline at 1 Year in the Study Eye as Compared With the Fellow Eye | -0.71 Percent change in cell density |
Comparison: No formal hypothesis testing was planned for this study. The paired t-tests were for reference purposes and thus not considered formal. The test was 2-sided, with the null hypothesis of no difference in percent change from baseline between the study eye and fellow eye in each patient.p-value: 0.770295% CI: [-1.14, 1.54]Paired t-test
Secondary
Substudy: Percent Change in Corneal Endothelial Cell Density From Baseline at Week 24 in the Study Eye as Compared With the Fellow Eye
Specular microscopy was performed for both eyes prior to application of any topical ophthalmic anesthetic, tonometry, or any other study treatment on the same day for the evaluation of corneal endothelial cell (CEC) density. The Week 24 timepoint was defined as the earliest substudy visit closest to Week 24 occurring between Week 20 and Week 28. Data (from both study eye and fellow eye) collected after the fellow eye's use of prohibited therapies-such as faricimab, brolucizumab, bevacizumab, and Port Delivery System implantation-were excluded from the corneal endothelial cell analysis.
Time frame: Baseline and Week 24
Population: Modified Intent-to-Treat Population: All enrolled participants who received at least one injection of faricimab in the study eye during this substudy. Only participants who completed the midpoint visit within the analysis window (Weeks 20 to 28) were included for analysis.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Main Study Cohort A: Faricimab PTI (Prior Faricimab) | Substudy: Percent Change in Corneal Endothelial Cell Density From Baseline at Week 24 in the Study Eye as Compared With the Fellow Eye | -0.02 Percent change in cell density |
| Main Study Cohort B: Faricimab PTI (Prior Aflibercept) | Substudy: Percent Change in Corneal Endothelial Cell Density From Baseline at Week 24 in the Study Eye as Compared With the Fellow Eye | -0.29 Percent change in cell density |
Comparison: No formal hypothesis testing was planned for this study. The paired t-tests were for reference purposes and thus not considered formal. The test was 2-sided, with the null hypothesis of no difference in percent change from baseline between the study eye and fellow eye in each patient.p-value: 0.630595% CI: [-0.84, 1.38]Paired t-test