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

Primary Purpose

Choroidal Neovascularization

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Faricimab

Ranibizumab

Sham Procedure

About this trial

This is an interventional treatment trial for Choroidal Neovascularization

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Active Comparator

Experimental

Arm Label

Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W)

Arm B: Faricimab, 1.5 mg Q4W

Arm C: Faricimab, 6 mg Q4W

Arm D: Faricimab, 6 mg Every 4-8 weeks

Arm E: Ranibizumab 0.5 mg + Faricimab 6 mg Q4W

Arm Description

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.

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.

Participants will receive faricimab 6 mg IVT Q4W up to Week 32 (9 injections). The final study visit will take place at Week 36.

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.

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.

Outcomes

Primary Outcome Measures

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.

Mean Change From Week 12 in BCVA Letter Score at Week 36, in Anti-VEGF Incomplete Responders

Secondary Outcome Measures

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.

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.

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.

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.

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.

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.

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.

Mean Change From Week 12 in Foveal Center Point Thickness at Week 36, as Measured by SD-OCT, in Anti-VEGF Incomplete Responders

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.

Mean Change From Week 12 in Central Subfield Thickness at Week 36, as Measured by SD-OCT in Anti-VEGF Incomplete Responders

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.

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.

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).

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.

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).

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.

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).

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.

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.

Number of Participants With at Least One Systemic Adverse Event by Highest Intensity, in All Participants

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.

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.

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.

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.

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

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

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.

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).

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.

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.

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.

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.

Full Information

NCT ID

NCT02484690

First Posted

June 12, 2015

Last Updated

October 20, 2020

Sponsor

Hoffmann-La Roche

1. Study Identification

Unique Protocol Identification Number

NCT02484690

Brief Title

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

Acronym

AVENUE

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

2. Study Status

Record Verification Date

October 2020

Overall Recruitment Status

Completed

Study Start Date

August 11, 2015 (Actual)

Primary Completion Date

September 26, 2017 (Actual)

Study Completion Date

September 26, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hoffmann-La Roche

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Choroidal Neovascularization

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

273 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm A: Ranibizumab, 0.5 mg Every 4 Weeks (Q4W)

Arm Type

Active Comparator

Arm Description

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.

Arm Title

Arm B: Faricimab, 1.5 mg Q4W

Arm Type

Experimental

Arm Description

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.

Arm Title

Arm C: Faricimab, 6 mg Q4W

Arm Type

Experimental

Arm Description

Participants will receive faricimab 6 mg IVT Q4W up to Week 32 (9 injections). The final study visit will take place at Week 36.

Arm Title

Arm D: Faricimab, 6 mg Every 4-8 weeks

Arm Type

Experimental

Arm Description

Arm Title

Arm E: Ranibizumab 0.5 mg + Faricimab 6 mg Q4W

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Faricimab

Other Intervention Name(s)

RO6867461, RG7716

Intervention Description

Faricimab will be administered as per the regimen specified in the individual arm.

Intervention Type

Drug

Intervention Name(s)

Ranibizumab

Other Intervention Name(s)

Lucentis

Intervention Description

Ranibizumab will be administered as per the regimen specified in the individual arm.

Intervention Type

Drug

Intervention Name(s)

Sham Procedure

Intervention Description

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.

Primary Outcome Measure Information:

Title

Mean Change From Baseline in BCVA Letter Score at Week 36, in Treatment-Naive Participants

Description

Time Frame

Baseline, Week 36

Title

Mean Change From Week 12 in BCVA Letter Score at Week 36, in Anti-VEGF Incomplete Responders

Description

Time Frame

Weeks 12 and 36

Secondary Outcome Measure Information:

Title

Percentage of Participants Gaining Greater Than or Equal to (≥) 15 Letters From Baseline in BCVA Letter Score at Week 36, in Treatment-Naive Participants

Description

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.

Time Frame

Baseline, Week 36

Title

Percentage of Participants Gaining ≥15 Letters From Week 12 in BCVA Letter Score at Week 36, in Anti-VEGF Incomplete Responders

Description

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.

Time Frame

Weeks 12 and 36

Title

Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better at Week 36, in Treatment-Naive Participants

Description

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.

Time Frame

Week 36

Title

Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better at Week 36, in Anti-VEGF Incomplete Responders

Description

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.

Time Frame

Week 36

Title

Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse at Week 36, in Treatment-Naive Participants

Description

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.

Time Frame

Week 36

Title

Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse at Week 36, in Anti-VEGF Incomplete Responders

Description

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.

Time Frame

Week 36

Title

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

Description

Time Frame

Baseline, Week 36

Title

Mean Change From Week 12 in Foveal Center Point Thickness at Week 36, as Measured by SD-OCT, in Anti-VEGF Incomplete Responders

Description

Time Frame

Weeks 12 and 36

Title

Mean Change From Baseline in Central Subfield Thickness at Week 36, as Measured by SD-OCT, in Treatment-Naive Participants

Description

Time Frame

Baseline, Week 36

Title

Mean Change From Week 12 in Central Subfield Thickness at Week 36, as Measured by SD-OCT in Anti-VEGF Incomplete Responders

Description

Time Frame

Weeks 12 and 36

Title

Description

Time Frame

Baseline, Week 36

Title

Description

Time Frame

Weeks 12 and 36

Title

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

Description

Time Frame

Baseline, Week 36

Title

Mean Change From Week 12 in Total Area of Choroidal Neovascularization (CNV) at Week 36, as Measured by FFA, in Anti-VEGF Incomplete Responders

Description

The total area of choroidal neovascularization (CNV) was evaluated by a central reading center using fundus fluorescein angiography (FFA).

Time Frame

Weeks 12 and 36

Title

Mean Change From Baseline in Total Area of Choroidal Neovascularization (CNV) Component at Week 36, as Measured by FFA, in Treatment-Naive Participants

Description

Time Frame

Baseline, Week 36

Title

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

Description

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).

Time Frame

Weeks 12 and 36

Title

Mean Change From Baseline in Total Area of Leakage at Week 36, as Measured by FFA, in Treatment-Naive Participants

Description

Time Frame

Baseline, Week 36

Title

Mean Change From Week 12 in Total Area of Leakage at Week 36, as Measured by FFA, in Anti-VEGF Incomplete Responders

Description

The total area of leakage was evaluated by a central reading center using fundus fluorescein angiography (FFA).

Time Frame

Weeks 12 and 36

Title

Safety Summary of the Overall Number of Participants With at Least One Adverse Event by Event Type, in All Participants

Description

Time Frame

From Baseline until 28 days after the last dose of study treatment (up to 36 weeks)

Title

Number of Participants With at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye by Highest Intensity, in All Participants

Description

Time Frame

From Baseline until 28 days after the last dose of study treatment (up to 36 weeks)

Title

Number of Participants With at Least One Systemic Adverse Event by Highest Intensity, in All Participants

Description

Time Frame

From Baseline until 28 days after the last dose of study treatment (up to 36 weeks)

Title

Number of Participants With Abnormal Systolic Blood Pressure, in All Participants

Description

Time Frame

Assessed at each study visit from Baseline until 28 days after the last dose of study treatment (up to 36 weeks)

Title

Number of Participants With Abnormal Diastolic Blood Pressure, in All Participants

Description

Time Frame

Assessed at each study visit from Baseline until 28 days after the last dose of study treatment (up to 36 weeks)

Title

Number of Participants With Abnormal Heart Rate, in All Participants

Description

Time Frame

Assessed at each study visit from Baseline until 28 days after the last dose of study treatment (up to 36 weeks)

Title

Number of Participants With Abnormal Body Temperature, in All Participants

Description

Time Frame

Assessed at each study visit from Baseline until 28 days after the last dose of study treatment (up to 36 weeks)

Title

Number of Participants With Marked Laboratory Abnormalities in Hematology and Coagulation Tests, in All Participants

Description

Time Frame

Predose at Baseline, Weeks 12 and 36, and at Early Termination and Unscheduled Visits (up to 36 weeks)

Title

Number of Participants With Marked Laboratory Abnormalities in Blood Chemistry Tests, in All Participants

Description

Time Frame

Predose at Baseline, Weeks 12 and 36, and at Early Termination and Unscheduled Visits (up to 36 weeks)

Title

Mean Change From Baseline in Intraocular Pressure in the Study Eye Over Time, in All Participants

Description

Time Frame

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

Title

Change From Baseline in the Number of Participants With Anti-Drug Antibodies to Faricimab at Any Post-Baseline Timepoint

Description

Blood samples were obtained for measurement of anti-faricimab antibodies by a validated enzyme-linked immunosorbent assay (ELISA).

Time Frame

Baseline, Predose (0 hour) on Days 1, 28, 84, 112, 168, and 252 or early termination (up to 36 weeks)

Title

Mean Plasma Concentration of Faricimab Over Time, in All Participants

Description

Time Frame

Predose (on days when treatment was administered) at Baseline and Weeks 4, 12, 13, 16, 24, and 36

Title

Mean Change From Baseline in Free Vascular Endothelial Growth Factor-A (VEGF-A) Plasma Concentrations Over Time, in All Participants

Description

Time Frame

Baseline, Weeks 4, 12, 13, 16, 24, and 36

Title

Mean Change From Baseline in Total Angiopoietin-2 (Ang-2) Plasma Concentrations Over Time, in All Participants

Description

Time Frame

Baseline, Weeks 4, 12, 13, 16, 24, and 36

Title

Mean Change From Baseline in Free Angiopoietin-2 (Ang-2) Plasma Concentrations Over Time, in All Participants

Description

Time Frame

Baseline, Weeks 4, 12, 13, 16, 24, and 36

10. Eligibility

Sex

All

Minimum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Trials

Organizational Affiliation

Hoffmann-La Roche

Official's Role

Study Director

Facility Information:

Facility Name

Associated Retina Consultants

City

Phoenix

State/Province

Arizona

ZIP/Postal Code

85020

Country

United States

Facility Name

Retinal Consultants of Arizona

City

Phoenix

State/Province

Arizona

ZIP/Postal Code

85053

Country

United States

Facility Name

California Retina Consultants

City

Bakersfield

State/Province

California

ZIP/Postal Code

93309

Country

United States

Facility Name

Retina-Vitreous Associates Medical Group

City

Beverly Hills

State/Province

California

ZIP/Postal Code

90211

Country

United States

Facility Name

The Retina Partners

City

Encino

State/Province

California

ZIP/Postal Code

91436

Country

United States

Facility Name

Retina Consultants, San Diego

City

Poway

State/Province

California

ZIP/Postal Code

92064

Country

United States

Facility Name

Orange County Retina Med Group

City

Santa Ana

State/Province

California

ZIP/Postal Code

92705

Country

United States

Facility Name

Bay Area Retina Associates

City

Walnut Creek

State/Province

California

ZIP/Postal Code

94598

Country

United States

Facility Name

American Institute of Research

City

Whittier

State/Province

California

ZIP/Postal Code

90603

Country

United States

Facility Name

Retina Consultants of Southern

City

Colorado Springs

State/Province

Colorado

ZIP/Postal Code

80909

Country

United States

Facility Name

Colorado Retina Associates, PC

City

Golden

State/Province

Colorado

ZIP/Postal Code

80401

Country

United States

Facility Name

New England Retina Associates

City

Hamden

State/Province

Connecticut

ZIP/Postal Code

06518

Country

United States

Facility Name

Retina Health Center

City

Fort Myers

State/Province

Florida

ZIP/Postal Code

33907

Country

United States

Facility Name

National Ophthalmic Research Institute

City

Fort Myers

State/Province

Florida

ZIP/Postal Code

33912

Country

United States

Facility Name

Florida Eye Associates

City

Melbourne

State/Province

Florida

ZIP/Postal Code

32901

Country

United States

Facility Name

Central Florida Retina

City

Orlando

State/Province

Florida

ZIP/Postal Code

32806

Country

United States

Facility Name

Retina Care Specialists

City

Palm Beach Gardens

State/Province

Florida

ZIP/Postal Code

33410

Country

United States

Facility Name

Retina Vitreous Assoc of FL

City

Saint Petersburg

State/Province

Florida

ZIP/Postal Code

33711

Country

United States

Facility Name

Southern Vitreoretinal Assoc

City

Tallahassee

State/Province

Florida

ZIP/Postal Code

32308

Country

United States

Facility Name

Southeast Retina Center

City

Augusta

State/Province

Georgia

ZIP/Postal Code

30909

Country

United States

Facility Name

Georgia Retina PC

City

Marietta

State/Province

Georgia

ZIP/Postal Code

30060

Country

United States

Facility Name

Midwest Eye Institute Northside

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46290

Country

United States

Facility Name

Paducah Retinal Center

City

Paducah

State/Province

Kentucky

ZIP/Postal Code

42001

Country

United States

Facility Name

Retina Group of Washington

City

Chevy Chase

State/Province

Maryland

ZIP/Postal Code

20815

Country

United States

Facility Name

National Retina Institute

City

Towson

State/Province

Maryland

ZIP/Postal Code

21204

Country

United States

Facility Name

Vitreo-Retinal Associates, PC

City

Worcester

State/Province

Massachusetts

ZIP/Postal Code

01605

Country

United States

Facility Name

Vitreoretinal Surgery

City

Edina

State/Province

Minnesota

ZIP/Postal Code

55435

Country

United States

Facility Name

Retina Associates of NJ

City

Toms River

State/Province

New Jersey

ZIP/Postal Code

08755

Country

United States

Facility Name

Eye Associates of New Mexico

City

Albuquerque

State/Province

New Mexico

ZIP/Postal Code

87102

Country

United States

Facility Name

Long Is. Vitreoretinal Consult

City

Great Neck

State/Province

New York

ZIP/Postal Code

11021

Country

United States

Facility Name

Opthalmic Consultants of LI

City

Lynbrook

State/Province

New York

ZIP/Postal Code

11563

Country

United States

Facility Name

Retina Assoc of Western NY

City

Rochester

State/Province

New York

ZIP/Postal Code

14620

Country

United States

Facility Name

The Retina Consultants

City

Slingerlands

State/Province

New York

ZIP/Postal Code

12159

Country

United States

Facility Name

Western Carolina Retinal Associate PA

City

Asheville

State/Province

North Carolina

ZIP/Postal Code

28803

Country

United States

Facility Name

Char Eye Ear &Throat Assoc

City

Charlotte

State/Province

North Carolina

ZIP/Postal Code

28210

Country

United States

Facility Name

OSU Eye Physicians & Surgeons

City

Columbus

State/Province

Ohio

ZIP/Postal Code

43212

Country

United States

Facility Name

Oregon Retina, LLP

City

Eugene

State/Province

Oregon

ZIP/Postal Code

97401

Country

United States

Facility Name

Oregon Retina institute

City

Medford

State/Province

Oregon

ZIP/Postal Code

97504

Country

United States

Facility Name

Retina Northwest

City

Portland

State/Province

Oregon

ZIP/Postal Code

97221

Country

United States

Facility Name

Mid Atlantic Retina

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19107

Country

United States

Facility Name

Palmetto Retina Center

City

West Columbia

State/Province

South Carolina

ZIP/Postal Code

29169

Country

United States

Facility Name

Southeastern Retina Associates Chattanooga

City

Chattanooga

State/Province

Tennessee

ZIP/Postal Code

37421

Country

United States

Facility Name

Charles Retina Institute

City

Germantown

State/Province

Tennessee

ZIP/Postal Code

38138

Country

United States

Facility Name

Tennessee Retina PC.

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37203

Country

United States

Facility Name

W Texas Retina Consultants PA

City

Abilene

State/Province

Texas

ZIP/Postal Code

79606

Country

United States

Facility Name

Austin Retina Associates

City

Austin

State/Province

Texas

ZIP/Postal Code

78705

Country

United States

Facility Name

Retina Research Center

City

Austin

State/Province

Texas

ZIP/Postal Code

78705

Country

United States

Facility Name

Retina Consultants of Houston

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Facility Name

Strategic Clinical Research Group, LLC

City

Willow Park

State/Province

Texas

ZIP/Postal Code

76087

Country

United States

Facility Name

Retina Associates of Utah

City

Salt Lake City

State/Province

Utah

ZIP/Postal Code

84107

Country

United States

Facility Name

Univ of Virginia Ophthalmology

City

Charlottesville

State/Province

Virginia

ZIP/Postal Code

22903

Country

United States

Facility Name

Spokane Eye Clinical Research

City

Spokane

State/Province

Washington

ZIP/Postal Code

99204

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

34201045

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.

Results Reference

derived

PubMed Identifier

32729888

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.

Results Reference

derived

Learn more about this trial

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

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

Choroidal Neovascularization

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial