Diabetic Macular Edema
Conditions
Brief summary
This is an exploratory, prospective, multicenter, open-label, single-arm, interventional, Phase IIb study designed to explore the associations over time between clinical assessments, multimodal imaging assessments, aqueous humor (AH) biomarker patterns, and genetic polymorphisms in participants with diabetic macular edema (DME) who are treated with faricimab.
Interventions
DRUGFaricimab
A 6-milligram (mg) dose of faricimab will be administered intravitreally (IVT) in the study eye once every 4 weeks (Q4W).
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of diabetes mellitus (Type 1 or Type 2), as defined by the World Health Organization (WHO) and/or American Diabetes Association * Hemoglobin A1c (HbA1c) ≤10% * Patients who are intravitreal (IVT) treatment-naïve in the study eye * Diabetic macular edema (DME) defined as macular thickening by spectral-domain optical coherence tomography (SD-OCT) involving the center of the macula. This inclusion criterion is to be assessed by the central reading center (CRC). * Decreased visual acuity (VA) attributable primarily to DME * Clear ocular media and adequate pupillary dilation to allow acquisition of good quality retinal images to confirm diagnosis
Exclusion criteria
* Currently untreated diabetes mellitus or previously untreated patients who initiated oral or injectable anti-diabetic medication within 3 months prior to Day 1 * Any known hypersensitivity to any of the components in the faricimab injection, dilating eye drops, or any of the anesthetics and antimicrobial preparations used by the patient during the study * Any major illness or major surgical procedure within 1 month before the Day 1. One re-screening for this criterion is permitted * History of other diseases, other non-diabetic metabolic dysfunction, physical examination finding, historical or current clinical laboratory finding giving reasonable suspicion of a condition that contraindicates the use of the faricimab or that might affect interpretation of the results of the study or renders the patient at high-risk for treatment complications, in the opinion of the Investigator * Active cancer within the past 12 months prior to Day 1 except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, and prostate cancer with a Gleason score of ≤6 and a stable prostate-specific antigen for \>12 months * Stroke or myocardial infarction within 12 months prior to the Day 1. One re-screening for this criterion is permitted * Any febrile illness within 1 week prior to Day 1. One re-screening for this criterion is permitted * Pregnant or breastfeeding, or intending to become pregnant during the study or within 3 months after the final dose of faricimab * Renal failure requiring renal transplant, hemodialysis, or peritoneal dialysis within 6 months prior to Day 1 or anticipated to require hemodialysis or peritoneal dialysis at any time during the study * Any condition resulting in a compromised immune system that is likely to impact the aqueous humor (AH) inflammatory biomarkers. * Patients who are currently enrolled in or have participated in any other clinical study involving an investigational product or device, or in any other type of medical research, within 3 months or 5 half-lives prior to Day 1 and up to completion of the current study * Substance abuse occurring within 12 months prior to screening, in the Investigator's judgment * Use of systemic immunomodulatory treatments within 6 months or 5 half-lives prior to Day 1 * Use of any systemic corticosteroids (including inhaled corticosteroids from inhalers used regularly, e.g., pulmonary disease, asthma, or seasonal allergy) within 1 month prior to Day 1 * Any prior or concomitant systemic anti-VEGF treatment within 6 months or 5 half-lives prior to Day 1 * Use of systemic medications known to be toxic to the lens, retina or optic nerve used during the 6-month period or 5 half-lives prior to Day 1 or likely need to be used * Received a blood transfusion within 3 months prior to the screening visit * Received any treatment that leads to immunosuppression within 6 months or 5 half-lives prior to Day 1 Ocular
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Baseline and Week 24 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adjusted Mean Change From Baseline in Best-Corrected Visual Acuity (BCVA) in the Study Eye at Week 24 | From Baseline to Week 24 | 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. |
| Adjusted Mean Change From Baseline in Central Subfield Thickness in the Study Eye at Week 24 | From Baseline to Week 24 | 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. |
| Median Time to First Absence of DME in the Study Eye During the Study | From Baseline to Week 24 | 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. |
| Percentage of Participants With Absence of Intraretinal Fluid in the Study Eye at Week 24 | Week 24 | 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. |
| Percentage of Participants With Absence of Subretinal Fluid in the Study Eye at Week 24 | Week 24 | 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. |
Countries
Argentina, Canada, Germany, Italy, Poland, United Kingdom, United States
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Participant flow
Recruitment details
A total of 99 patients were enrolled in the study at 23 sites in 7 countries.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 99 |
| Total | 99 |
Baseline characteristics
| Characteristic | Faricimab |
|---|---|
| Age, Continuous | 59.5 Years STANDARD_DEVIATION 9.8 |
| Best-Corrected Visual Acuity (BCVA) in the Study Eye at Baseline | 62.5 ETDRS Letters STANDARD_DEVIATION 11.8 |
| Central Subfield Thickness (CST) in the Study Eye at Baseline | 464.0 microns STANDARD_DEVIATION 149.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 25 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 73 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race/Ethnicity, Customized Asian | 5 Participants |
| Race/Ethnicity, Customized Black or African American | 7 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants |
| Race/Ethnicity, Customized White | 86 Participants |
| Region of Enrollment Rest of the World | 37 Participants |
| Region of Enrollment US and Canada | 62 Participants |
| Sex: Female, Male Female | 38 Participants |
| Sex: Female, Male Male | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 99 |
| other Total, other adverse events | 21 / 99 |
| serious Total, serious adverse events | 8 / 99 |
Outcome results
Primary
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
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Faricimab | 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 |
Secondary
Adjusted Mean Change From Baseline in Best-Corrected Visual Acuity (BCVA) in the Study Eye at Week 24
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Faricimab | Adjusted Mean Change From Baseline in Best-Corrected Visual Acuity (BCVA) in the Study Eye at Week 24 | 9.2 ETDRS Letters |
Secondary
Adjusted Mean Change From Baseline in Central Subfield Thickness in the Study Eye at Week 24
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Faricimab | Adjusted Mean Change From Baseline in Central Subfield Thickness in the Study Eye at Week 24 | -200.2 microns |
Secondary
Median Time to First Absence of DME in the Study Eye During the Study
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Faricimab | Median Time to First Absence of DME in the Study Eye During the Study | 8.0 Weeks |
Secondary
Percentage of Participants With Absence of Intraretinal Fluid in the Study Eye at Week 24
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.
Time frame: Week 24
Population: Participants in the modified intent-to-treat (mITT) Population with non-missing Week 24 assessments were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Faricimab | Percentage of Participants With Absence of Intraretinal Fluid in the Study Eye at Week 24 | 26.1 Percentage of participants |
Secondary
Percentage of Participants With Absence of Subretinal Fluid in the Study Eye at Week 24
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.
Time frame: Week 24
Population: Participants in the modified intent-to-treat (mITT) Population with non-missing Week 24 assessments were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Faricimab | Percentage of Participants With Absence of Subretinal Fluid in the Study Eye at Week 24 | 98.9 Percentage of participants |