Trial Outcomes & Findings for A Study to Investigate Aqueous Humor and Multimodal Imaging Biomarkers in Treatment-Naïve Participants With Diabetic Macular Edema Treated With Faricimab (NCT NCT04597918)

Last Updated: 2023-12-01

Results Overview

The ETDRS DRSS score of each participant's study eye was assessed using ultra-wide field color fundus photography (UWF-CFP) taken by trained personnel at the study sites. Analysis of the fundus photographs was performed by the central reading center, and the percentage of participants with a ≥2-step improvement from baseline was summarized along with a two-sided 95% Clopper-Pearson exact confidence interval. Baseline was defined as the participant's last observation prior to initiation of study drug.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

99 participants

Primary outcome timeframe

Baseline and Week 24

Results posted on

2023-12-01

Participant Flow

A total of 99 patients were enrolled in the study at 23 sites in 7 countries.

Participant milestones

Participant milestones
Measure	Faricimab Participants received 6 doses of faricimab (one 6-mg faricimab intravitreal \[IVT\] injection every 28 days \[Q4W\]) starting at Day 1 and ending on the Day 140 visit. Participants returned for a safety follow-up visit (SFV) after ≥28 days and within \<35 days following their last study treatment.
Overall Study STARTED	99
Overall Study COMPLETED	89
Overall Study NOT COMPLETED	10

Reasons for withdrawal

Reasons for withdrawal
Measure	Faricimab Participants received 6 doses of faricimab (one 6-mg faricimab intravitreal \[IVT\] injection every 28 days \[Q4W\]) starting at Day 1 and ending on the Day 140 visit. Participants returned for a safety follow-up visit (SFV) after ≥28 days and within \<35 days following their last study treatment.
Overall Study Withdrawal by Subject	6
Overall Study Lost to Follow-up	3
Overall Study Death	1

Baseline Characteristics

A Study to Investigate Aqueous Humor and Multimodal Imaging Biomarkers in Treatment-Naïve Participants With Diabetic Macular Edema Treated With Faricimab

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Faricimab n=99 Participants Participants received 6 doses of faricimab (one 6-mg faricimab intravitreal \[IVT\] injection every 28 days \[Q4W\]) starting at Day 1 and ending on the Day 140 visit. Participants returned for a safety follow-up visit (SFV) after ≥28 days and within \<35 days following their last study treatment.
Age, Continuous	59.5 Years STANDARD_DEVIATION 9.8 • n=5 Participants
Sex: Female, Male Female	38 Participants n=5 Participants
Sex: Female, Male Male	61 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	25 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	73 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	7 Participants n=5 Participants
Race/Ethnicity, Customized White	86 Participants n=5 Participants
Race/Ethnicity, Customized Asian	5 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	1 Participants n=5 Participants
Region of Enrollment US and Canada	62 Participants n=5 Participants
Region of Enrollment Rest of the World	37 Participants n=5 Participants
Best-Corrected Visual Acuity (BCVA) in the Study Eye at Baseline	62.5 ETDRS Letters STANDARD_DEVIATION 11.8 • n=5 Participants
Central Subfield Thickness (CST) in the Study Eye at Baseline	464.0 microns STANDARD_DEVIATION 149.5 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 24

Population: Participants in the modified intent-to-treat (mITT) Population with missing baseline assessments were excluded from the analysis. The number analyzed indicates participants with assessments at both Baseline and Week 24.

Outcome measures

Outcome measures
Measure	Faricimab n=64 Participants Participants received 6 doses of faricimab (one 6-mg faricimab intravitreal \[IVT\] injection every 28 days \[Q4W\]) starting at Day 1 and ending on the Day 140 visit. Participants returned for a safety follow-up visit (SFV) after ≥28 days and within \<35 days following their last study treatment.
Percentage of Participants With a ≥2-Step Improvement From Baseline on the Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) in the Study Eye at Week 24	50.0 Percentage of participants Interval 37.2 to 62.8

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: The modified intent-to-treat (mITT) population is defined as all participants enrolled in the study that received any amount of study treatment.

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. For the Mixed Model for Repeated Measures (MMRM) analysis, the model adjusted for visit, age (continuous), baseline BCVA (continuous), and region (US and Canada and the rest of the world). An unstructured covariance structure was used. In case of convergence issues with the model, an AR (1) covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM.

Outcome measures

Outcome measures
Measure	Faricimab n=99 Participants Participants received 6 doses of faricimab (one 6-mg faricimab intravitreal \[IVT\] injection every 28 days \[Q4W\]) starting at Day 1 and ending on the Day 140 visit. Participants returned for a safety follow-up visit (SFV) after ≥28 days and within \<35 days following their last study treatment.
Adjusted Mean Change From Baseline in Best-Corrected Visual Acuity (BCVA) in the Study Eye at Week 24	9.2 ETDRS Letters Interval 7.5 to 10.9

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: The modified intent-to-treat (mITT) population is defined as all participants enrolled in the study that received any amount of study treatment.

Central subfield thickness (CST) was defined as the distance between the internal limiting membrane (ILM) and the retinal pigment epithelium (RPE) using Spectral Domain-Optical Coherence Tomography (SD-OCT), as assessed by the central reading center. For the Mixed Model of Repeated Measures (MMRM) analysis, the model was adjusted for visit, age (continuous), baseline CST (continuous), and region (US and Canada and the rest of the world). An unstructured covariance structure was used. In case of convergence issues with the model, an AR (1) covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM.

Outcome measures

Outcome measures
Measure	Faricimab n=99 Participants Participants received 6 doses of faricimab (one 6-mg faricimab intravitreal \[IVT\] injection every 28 days \[Q4W\]) starting at Day 1 and ending on the Day 140 visit. Participants returned for a safety follow-up visit (SFV) after ≥28 days and within \<35 days following their last study treatment.
Adjusted Mean Change From Baseline in Central Subfield Thickness in the Study Eye at Week 24	-200.2 microns Interval -214.1 to -186.2

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: The modified intent-to-treat (mITT) population is defined as all participants enrolled in the study that received any amount of study treatment. Participants with absence of DME at Baseline were excluded from the analysis.

An event was defined as the first absence of diabetic macular edema (DME) in the study eye, defined as first time reaching central subfield thickness (CST; ILM-RPE) \<305 microns, after baseline. Baseline was defined as the participant's last observation prior to initiation of study drug. The time to first absence of DME was a Kaplan-Meier estimate. The 95% confidence interval (CI) for the median was computed using the method of Brookmeyer and Crowley. Participants without an event and discontinued from treatment were censored at the last CST assessment.

Outcome measures

Outcome measures
Measure	Faricimab n=98 Participants Participants received 6 doses of faricimab (one 6-mg faricimab intravitreal \[IVT\] injection every 28 days \[Q4W\]) starting at Day 1 and ending on the Day 140 visit. Participants returned for a safety follow-up visit (SFV) after ≥28 days and within \<35 days following their last study treatment.
Median Time to First Absence of DME in the Study Eye During the Study	8.0 Weeks Interval 8.0 to 12.0

SECONDARY outcome

Timeframe: Week 24

Population: Participants in the modified intent-to-treat (mITT) Population with non-missing Week 24 assessments were included in the analysis.

The absence of intraretinal fluid (IRF) in the study eye (defined as IRF absent or definite outside center subfield only) was assessed by the central reading center using Spectral Domain-Optical Coherence Tomography (SD-OCT). The percentage of participants with absence of IRF and a two-sided 95% Clopper-Pearson exact confidence interval are reported.

Outcome measures

Outcome measures
Measure	Faricimab n=88 Participants Participants received 6 doses of faricimab (one 6-mg faricimab intravitreal \[IVT\] injection every 28 days \[Q4W\]) starting at Day 1 and ending on the Day 140 visit. Participants returned for a safety follow-up visit (SFV) after ≥28 days and within \<35 days following their last study treatment.
Percentage of Participants With Absence of Intraretinal Fluid in the Study Eye at Week 24	26.1 Percentage of participants Interval 17.3 to 36.6

SECONDARY outcome

Timeframe: Week 24

Population: Participants in the modified intent-to-treat (mITT) Population with non-missing Week 24 assessments were included in the analysis.

The absence of subretinal fluid (SRF) in the study eye (defined as SRF absent or definite outside center subfield only) was assessed by the central reading center using Spectral Domain-Optical Coherence Tomography (SD-OCT). The percentage of participants with absence of SRF and a two-sided 95% Clopper-Pearson exact confidence interval are reported.

Outcome measures

Outcome measures
Measure	Faricimab n=88 Participants Participants received 6 doses of faricimab (one 6-mg faricimab intravitreal \[IVT\] injection every 28 days \[Q4W\]) starting at Day 1 and ending on the Day 140 visit. Participants returned for a safety follow-up visit (SFV) after ≥28 days and within \<35 days following their last study treatment.
Percentage of Participants With Absence of Subretinal Fluid in the Study Eye at Week 24	98.9 Percentage of participants Interval 93.8 to 100.0

Adverse Events

Faricimab

Serious events: 8 serious events

Other events: 21 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Faricimab n=99 participants at risk Participants received 6 doses of faricimab (one 6-mg faricimab intravitreal \[IVT\] injection every 28 days \[Q4W\]) starting at Day 1 and ending on the Day 140 visit. Participants returned for a safety follow-up visit (SFV) after ≥28 days and within \<35 days following their last study treatment.
Infections and infestations Localised infection	2.0% 2/99 • Number of events 2 • From first dose of study drug until ≥28 days to <35 days after the last dose of study drug (up to 24 weeks) Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of faricimab in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.
Infections and infestations Sepsis	2.0% 2/99 • Number of events 2 • From first dose of study drug until ≥28 days to <35 days after the last dose of study drug (up to 24 weeks) Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of faricimab in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.
Infections and infestations COVID-19	1.0% 1/99 • Number of events 1 • From first dose of study drug until ≥28 days to <35 days after the last dose of study drug (up to 24 weeks) Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of faricimab in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.
Infections and infestations Cellulitis	1.0% 1/99 • Number of events 1 • From first dose of study drug until ≥28 days to <35 days after the last dose of study drug (up to 24 weeks) Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of faricimab in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.
Infections and infestations Escherichia urinary tract infection	1.0% 1/99 • Number of events 1 • From first dose of study drug until ≥28 days to <35 days after the last dose of study drug (up to 24 weeks) Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of faricimab in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.
Infections and infestations Osteomyelitis	1.0% 1/99 • Number of events 1 • From first dose of study drug until ≥28 days to <35 days after the last dose of study drug (up to 24 weeks) Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of faricimab in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.
Cardiac disorders Acute myocardial infarction	1.0% 1/99 • Number of events 1 • From first dose of study drug until ≥28 days to <35 days after the last dose of study drug (up to 24 weeks) Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of faricimab in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.
Cardiac disorders Coronary artery disease	1.0% 1/99 • Number of events 1 • From first dose of study drug until ≥28 days to <35 days after the last dose of study drug (up to 24 weeks) Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of faricimab in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.
Surgical and medical procedures Spinal operation	1.0% 1/99 • Number of events 1 • From first dose of study drug until ≥28 days to <35 days after the last dose of study drug (up to 24 weeks) Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of faricimab in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.
Surgical and medical procedures Toe amputation	1.0% 1/99 • Number of events 1 • From first dose of study drug until ≥28 days to <35 days after the last dose of study drug (up to 24 weeks) Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of faricimab in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.
Injury, poisoning and procedural complications Fall	1.0% 1/99 • Number of events 1 • From first dose of study drug until ≥28 days to <35 days after the last dose of study drug (up to 24 weeks) Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of faricimab in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.

Other adverse events

Other adverse events
Measure	Faricimab n=99 participants at risk Participants received 6 doses of faricimab (one 6-mg faricimab intravitreal \[IVT\] injection every 28 days \[Q4W\]) starting at Day 1 and ending on the Day 140 visit. Participants returned for a safety follow-up visit (SFV) after ≥28 days and within \<35 days following their last study treatment.
Eye disorders Diabetic retinal oedema	6.1% 6/99 • Number of events 6 • From first dose of study drug until ≥28 days to <35 days after the last dose of study drug (up to 24 weeks) Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of faricimab in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.
Eye disorders Retinal exudates	5.1% 5/99 • Number of events 10 • From first dose of study drug until ≥28 days to <35 days after the last dose of study drug (up to 24 weeks) Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of faricimab in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.
Infections and infestations COVID-19	7.1% 7/99 • Number of events 7 • From first dose of study drug until ≥28 days to <35 days after the last dose of study drug (up to 24 weeks) Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of faricimab in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.
Vascular disorders Hypertension	5.1% 5/99 • Number of events 5 • From first dose of study drug until ≥28 days to <35 days after the last dose of study drug (up to 24 weeks) Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of faricimab in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800-821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The study being conducted under this agreement is part of the overall study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the study, but only after the first publication or presentation that involves the overall study. The Sponsor may request that confidential information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER