Nonproliferative Diabetic Retinopathy
Conditions
Brief summary
The purpose of this study is to evaluate the safety and efficacy of subcutaneously administered AKB-9778 15mg once daily or 15mg twice daily for 12 months in patients with moderate to severe non-proliferative diabetic retinopathy (NPDR).
Interventions
DRUGAKB-9778
Subcutaneous AKB-9778 15mg
DRUGPlacebo
Subcutaneous Placebo
Sponsors
EyePoint Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Adults 18 through 80 years of age (inclusive) * Subjects with moderate to very severe NPDR (ETDRS Level 43 - 53 inclusive) * No evidence of central involved diabetic macular edema * ETDRS best-corrected visual acuity letter score ≥ 70 (Snellen 20/40 or better) Key
Exclusion criteria
* Ocular disease other than DR that may cause substantial reduction in visual acuity, including iris neovascularization, retinal detachment, visually significant epiretinal membrane, vitreous hemorrhage or fibrosis, ocular inflammation (uveitis), other retinal inflammatory or infectious diseases * Evidence of neovascularization on clinical examination or imaging * Hemoglobin A1C (HbA1C) ≥ 12.0% at Screening * Severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With an Improvement in Study Eye Severity of Diabetic Retinopathy (DR) (ETDRS DR Severity Score or DRSS) of ≥ 2 Steps | Baseline to Week 48 | Change from baseline to Week 48 in Diabetic Retinopathy Severity Scale Score in Study Eye by visit in the modified intent-to-treat population. ETDRS DR severity levels 10-85; ETDRS Steps 1-12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in DRSS in the Study Eye at Week 48 | Week 48 | Mean change from baseline in Diabetic Retinopathy Severity Score (DRSS) in the study eye at week 48. Note: Observed values at Week 48 instead of change from baseline values at Week 48 were analyzed Grading will follow Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) criteria. DRSS grades ranging from 10-85 will be converted to an ordinal score ranging from 1-11. ETDRS DRSS Level 10 = No retinopathy ETDRS DRSS Level 20 = Very mild NPDR ETDRS DRSS Level 35 = Mild NPDR ETDRS DRSS Level 43 = Moderate NPDR ETDRS DRSS Level 53 = Severe NPDR ETDRS DRSS Level 61 = Mild PDR ETDRS DRSS Level 65 = Moderate PDR ETDRS DRSS Level 71-75 = High-Risk PDR ETDRS DRSS Level 81-85 = Advanced PDR |
| Summary of Subjects With an Improvement or Worsening in the Study Eye DRSS of ≥ 3 Steps at Week 48. | Baseline to Week 48 | Summary of subjects with an improvement or worsening in the study eye Diabetic Retinopathy Severity Score (DRSS) of ≥ 3 steps at Week 48 (compared to placebo) Grading will follow Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) criteria. DRSS grades ranging from 10-85 will be converted to an ordinal score ranging from 1-11. ETDRS DRSS Level 10 = No retinopathy ETDRS DRSS Level 20 = Very mild NPDR ETDRS DRSS Level 35 = Mild NPDR ETDRS DRSS Level 43 = Moderate NPDR ETDRS DRSS Level 53 = Severe NPDR ETDRS DRSS Level 61 = Mild PDR ETDRS DRSS Level 65 = Moderate PDR ETDRS DRSS Level 71-75 = High-Risk PDR ETDRS DRSS Level 81-85 = Advanced PDR |
| Subjects With Criterion Step Improvement in DRSS at Week 48/EOT (>=2 Steps Improvement in the Study Eye for Patients With Non-qualified Fellow Eye and >=3 Steps Improvement on the Person Scale for Patients With Qualified Fellow Eyes) | Treatment Period - 12 months (48 weeks) | Subjects with Criterion Step Improvement in Diabetic Retinopathy Severity Score (DRSS) at Week 48/EOT (\>=2 Steps Improvement in the Study Eye for Patients with Non-qualified Fellow Eye and \>=3 Steps Improvement on the Person Scale for Patients with Qualified Fellow Eyes). Grading will follow Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) criteria. DRSS grades ranging from 10-85 will be converted to an ordinal score ranging from 1-11. ETDRS DRSS Level 10 = No retinopathy ETDRS DRSS Level 20 = Very mild NPDR ETDRS DRSS Level 35 = Mild NPDR ETDRS DRSS Level 43 = Moderate NPDR ETDRS DRSS Level 53 = Severe NPDR ETDRS DRSS Level 61 = Mild PDR ETDRS DRSS Level 65 = Moderate PDR ETDRS DRSS Level 71-75 = High-Risk PDR ETDRS DRSS Level 81-85 = Advanced PDR |
| Summary of Subjects With a Worsening in the Study Eye DRSS of ≥ 2 Steps at Week 48 | Baseline to Week 48 | Worsening of Diabetic Retinopathy Severity Score (DRSS) severity of ≥ 2 steps in study eyes at Week 48 (compared to placebo group) Grading will follow Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) criteria. DRSS grades ranging from 10-85 will be converted to an ordinal score ranging from 1-11. ETDRS DRSS Level 10 = No retinopathy ETDRS DRSS Level 20 = Very mild NPDR ETDRS DRSS Level 35 = Mild NPDR ETDRS DRSS Level 43 = Moderate NPDR ETDRS DRSS Level 53 = Severe NPDR ETDRS DRSS Level 61 = Mild PDR ETDRS DRSS Level 65 = Moderate PDR ETDRS DRSS Level 71-75 = High-Risk PDR ETDRS DRSS Level 81-85 = Advanced PDR |
| Summary of Patients Developing Center-involved DME or PDR or PDR-related Outcomes During Treatment Period Based on Clinical Data. | Treatment Period - 12 months (48 weeks) | Summary of patients developing center-involved Diabetic Macular Edema (DME) or Proliferative Diabetic Retinopathy (PDR) or PDR-related outcomes during treatment period based on Clinical Data. Based on either clinical data or central image reading center evaluation. |
| Summary of Subjects Developing Center-involved DME or PDR or Worsening of >=2 Steps DRSS at Week 48 Based on Central Image Reading Center Evaluation | Treatment Period - 12 months (48 weeks) | Summary of Subjects Developing Center-involved Diabetic Macular Edema (DME) or Proliferative Diabetic Retinopathy (PDR) or Worsening of \>=2 Steps Diabetic Retinopathy Severity Scale (DRSS) at Week 48 Based on Central Image Reading Center Evaluation - Study Eyes Grading will follow Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) criteria. DRSS grades ranging from 10-85 will be converted to an ordinal score ranging from 1-11. ETDRS DRSS Level 10 = No retinopathy ETDRS DRSS Level 20 = Very mild NPDR ETDRS DRSS Level 35 = Mild NPDR ETDRS DRSS Level 43 = Moderate NPDR ETDRS DRSS Level 53 = Severe NPDR ETDRS DRSS Level 61 = Mild PDR ETDRS DRSS Level 65 = Moderate PDR ETDRS DRSS Level 71-75 = High-Risk PDR ETDRS DRSS Level 81-85 = Advanced PDR |
| Subjects With Criterion Step Improvement in DRSS at Week 48/EOT (>=2 Steps Improvement in the Study Eye for Patients With Non-qualified Fellow Eye and >=3 Steps Improvement on the Binocular Scale for Patients With Qualified Fellow Eyes) | Treatment Period - 12 months (48 weeks) | Subjects With Criterion Step Improvement in Diabetic Retinopathy Severity Score (DRSS) at Week 48/EOT (\>=2 Steps Improvement in the Study Eye for Patients With Non-qualified Fellow Eye and \>=3 Steps Improvement on the Binocular Scale for Patients With Qualified Fellow Eyes). Grading will follow Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) criteria. DRSS grades ranging from 10-85 will be converted to an ordinal score ranging from 1-11. ETDRS DRSS Level 10 = No retinopathy ETDRS DRSS Level 20 = Very mild NPDR ETDRS DRSS Level 35 = Mild NPDR ETDRS DRSS Level 43 = Moderate NPDR ETDRS DRSS Level 53 = Severe NPDR ETDRS DRSS Level 61 = Mild PDR ETDRS DRSS Level 65 = Moderate PDR ETDRS DRSS Level 71-75 = High-Risk PDR ETDRS DRSS Level 81-85 = Advanced PDR |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Razuprotafib 15mg Twice Daily Razuprotafib: Subcutaneous Razuprotafib 15mg | 55 |
| Razuprotafib 15mg Daily Razuprotafib: Subcutaneous Razuprotafib 15mg
Placebo: Subcutaneous Placebo | 55 |
| Placebo Twice Daily Placebo: Subcutaneous Placebo | 57 |
| Total | 167 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 9 | 4 | 6 |
| Overall Study | data not available | 1 | 1 | 0 |
| Overall Study | Lost to Follow-up | 2 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 3 | 0 |
Baseline characteristics
| Characteristic | Razuprotafib 15mg Twice Daily | Total | Placebo Twice Daily | Razuprotafib 15mg Daily |
|---|---|---|---|---|
| Age, Continuous | 56.7 years STANDARD_DEVIATION 11.17 | 57.0 years STANDARD_DEVIATION 10.58 | 55.9 years STANDARD_DEVIATION 9.88 | 58.5 years STANDARD_DEVIATION 10.69 |
| Best-Corrected Visual Acuity in Study Eye, Letters | 82.4 letter score STANDARD_DEVIATION 5.41 | 82.7 letter score STANDARD_DEVIATION 6.06 | 83.5 letter score STANDARD_DEVIATION 6.33 | 82.2 letter score STANDARD_DEVIATION 6.4 |
| Body Mass Index, kg/m² | 31.91 kg/m² STANDARD_DEVIATION 4.776 | 30.71 kg/m² STANDARD_DEVIATION 4.949 | 30.58 kg/m² STANDARD_DEVIATION 4.752 | 29.63 kg/m² STANDARD_DEVIATION 5.138 |
| Diabetic Retinopathy Severity Scale Score in Study Eye | 4.8 units on a scale STANDARD_DEVIATION 0.7 | 4.9 units on a scale STANDARD_DEVIATION 0.69 | 4.9 units on a scale STANDARD_DEVIATION 0.68 | 4.9 units on a scale STANDARD_DEVIATION 0.7 |
| Duration of Diabetes, years | 17.83 years STANDARD_DEVIATION 12.232 | 16.69 years STANDARD_DEVIATION 10.749 | 14.54 years STANDARD_DEVIATION 8.625 | 17.78 years STANDARD_DEVIATION 11.001 |
| Duration of non-proliferative diabetic retinopathy in Study Eye, years | 2.69 years STANDARD_DEVIATION 4.36 | 2.43 years STANDARD_DEVIATION 3.841 | 2.55 years STANDARD_DEVIATION 4.267 | 2.04 years STANDARD_DEVIATION 2.679 |
| Duration of NPDR in qualified fellow eye, years | 1.78 years STANDARD_DEVIATION 2.54 | 2.00 years STANDARD_DEVIATION 2.75 | 2.14 years STANDARD_DEVIATION 2.512 | 2.00 years STANDARD_DEVIATION 3.282 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 25 Participants | 70 Participants | 25 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants | 97 Participants | 32 Participants | 35 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Hemoglobin A1c, % | 8.58 % of Glycated hemoglobin STANDARD_DEVIATION 1.38 | 8.35 % of Glycated hemoglobin STANDARD_DEVIATION 1.587 | 8.18 % of Glycated hemoglobin STANDARD_DEVIATION 1.457 | 8.31 % of Glycated hemoglobin STANDARD_DEVIATION 1.885 |
| Prior Treatment for PDR or DME in Qualified Fellow Eye No | 12 Participants | 47 Participants | 17 Participants | 18 Participants |
| Prior Treatment for PDR or DME in Qualified Fellow Eye Yes | 1 Participants | 8 Participants | 5 Participants | 2 Participants |
| Prior Treatment for Proliferative Diabetic Retinopathy or Diabetic Macular Edema in Study Eye No | 41 Participants | 139 Participants | 50 Participants | 48 Participants |
| Prior Treatment for Proliferative Diabetic Retinopathy or Diabetic Macular Edema in Study Eye Yes | 14 Participants | 28 Participants | 7 Participants | 7 Participants |
| Race/Ethnicity, Customized American Indian/Native Alaskan | 1 Participants | 3 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 6 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Black/African American | 4 Participants | 14 Participants | 3 Participants | 7 Participants |
| Race/Ethnicity, Customized Native Hawaiian/Pacific Islander | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 2 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 47 Participants | 141 Participants | 49 Participants | 45 Participants |
| Sex: Female, Male Female | 23 Participants | 71 Participants | 25 Participants | 23 Participants |
| Sex: Female, Male Male | 32 Participants | 96 Participants | 32 Participants | 32 Participants |
| Study eye, n (%) Left Eye | 28 Participants | 82 Participants | 31 Participants | 23 Participants |
| Study eye, n (%) Right Eye | 27 Participants | 85 Participants | 26 Participants | 32 Participants |
| Taking Angiotensin-Converting Enzyme Inhibitor (ACEi)/Angiotensin Receptor Blocker (ARB) No | 26 Participants | 66 Participants | 24 Participants | 16 Participants |
| Taking Angiotensin-Converting Enzyme Inhibitor (ACEi)/Angiotensin Receptor Blocker (ARB) Yes | 29 Participants | 101 Participants | 33 Participants | 39 Participants |
| Taking Insulin, n (%) No | 12 Participants | 54 Participants | 24 Participants | 18 Participants |
| Taking Insulin, n (%) Yes | 43 Participants | 113 Participants | 33 Participants | 37 Participants |
| Type of Diabetes, n (%) Type 1 | 6 Participants | 16 Participants | 4 Participants | 6 Participants |
| Type of Diabetes, n (%) Type 2 | 49 Participants | 151 Participants | 53 Participants | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 55 | 0 / 55 | 1 / 57 |
| other Total, other adverse events | 55 / 55 | 55 / 55 | 57 / 57 |
| serious Total, serious adverse events | 8 / 55 | 6 / 55 | 5 / 57 |
Outcome results
Primary
Percentage of Subjects With an Improvement in Study Eye Severity of Diabetic Retinopathy (DR) (ETDRS DR Severity Score or DRSS) of ≥ 2 Steps
Change from baseline to Week 48 in Diabetic Retinopathy Severity Scale Score in Study Eye by visit in the modified intent-to-treat population. ETDRS DR severity levels 10-85; ETDRS Steps 1-12
Time frame: Baseline to Week 48
Population: The modified intent-to-treat population consisted of all enrolled subjects who received at least 1 dose of study medication and was the population used for the efficacy population.
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| Razuprotafib 15mg Twice Daily | Percentage of Subjects With an Improvement in Study Eye Severity of Diabetic Retinopathy (DR) (ETDRS DR Severity Score or DRSS) of ≥ 2 Steps | 0 eyes |
| Razuprotafib 15mg Daily | Percentage of Subjects With an Improvement in Study Eye Severity of Diabetic Retinopathy (DR) (ETDRS DR Severity Score or DRSS) of ≥ 2 Steps | 5 eyes |
| Placebo Twice Daily | Percentage of Subjects With an Improvement in Study Eye Severity of Diabetic Retinopathy (DR) (ETDRS DR Severity Score or DRSS) of ≥ 2 Steps | 2 eyes |
Comparison: The primary hypotheses tested was that razuprotafib 15 mg twice daily and razuprotafib 15 mg once daily will be superior to placebo in the improvement of diabetic retinopathy as measured by the Early Treatment Diabetic Retinopathy Study severity scale change from baseline at 48 weeks.p-value: 0.495Fisher Exact
Secondary
Mean Change From Baseline in DRSS in the Study Eye at Week 48
Mean change from baseline in Diabetic Retinopathy Severity Score (DRSS) in the study eye at week 48. Note: Observed values at Week 48 instead of change from baseline values at Week 48 were analyzed Grading will follow Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) criteria. DRSS grades ranging from 10-85 will be converted to an ordinal score ranging from 1-11. ETDRS DRSS Level 10 = No retinopathy ETDRS DRSS Level 20 = Very mild NPDR ETDRS DRSS Level 35 = Mild NPDR ETDRS DRSS Level 43 = Moderate NPDR ETDRS DRSS Level 53 = Severe NPDR ETDRS DRSS Level 61 = Mild PDR ETDRS DRSS Level 65 = Moderate PDR ETDRS DRSS Level 71-75 = High-Risk PDR ETDRS DRSS Level 81-85 = Advanced PDR
Time frame: Week 48
Population: Modified Intent-to-Treat Population With at Least 1 Scheduled Post-Baseline Measure (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Razuprotafib 15mg Twice Daily | Mean Change From Baseline in DRSS in the Study Eye at Week 48 | 5.0 score on a scale | Standard Deviation 1.15 |
| Razuprotafib 15mg Daily | Mean Change From Baseline in DRSS in the Study Eye at Week 48 | 4.9 score on a scale | Standard Deviation 1.55 |
| Placebo Twice Daily | Mean Change From Baseline in DRSS in the Study Eye at Week 48 | 4.8 score on a scale | Standard Deviation 1.35 |
Secondary
Subjects With Criterion Step Improvement in DRSS at Week 48/EOT (>=2 Steps Improvement in the Study Eye for Patients With Non-qualified Fellow Eye and >=3 Steps Improvement on the Binocular Scale for Patients With Qualified Fellow Eyes)
Subjects With Criterion Step Improvement in Diabetic Retinopathy Severity Score (DRSS) at Week 48/EOT (\>=2 Steps Improvement in the Study Eye for Patients With Non-qualified Fellow Eye and \>=3 Steps Improvement on the Binocular Scale for Patients With Qualified Fellow Eyes). Grading will follow Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) criteria. DRSS grades ranging from 10-85 will be converted to an ordinal score ranging from 1-11. ETDRS DRSS Level 10 = No retinopathy ETDRS DRSS Level 20 = Very mild NPDR ETDRS DRSS Level 35 = Mild NPDR ETDRS DRSS Level 43 = Moderate NPDR ETDRS DRSS Level 53 = Severe NPDR ETDRS DRSS Level 61 = Mild PDR ETDRS DRSS Level 65 = Moderate PDR ETDRS DRSS Level 71-75 = High-Risk PDR ETDRS DRSS Level 81-85 = Advanced PDR
Time frame: Treatment Period - 12 months (48 weeks)
Population: Modified Intent-to-Treat Population with at least 1 scheduled Post-Baseline Measure (LOCF)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Razuprotafib 15mg Twice Daily | Subjects With Criterion Step Improvement in DRSS at Week 48/EOT (>=2 Steps Improvement in the Study Eye for Patients With Non-qualified Fellow Eye and >=3 Steps Improvement on the Binocular Scale for Patients With Qualified Fellow Eyes) | 0 Participants |
| Razuprotafib 15mg Daily | Subjects With Criterion Step Improvement in DRSS at Week 48/EOT (>=2 Steps Improvement in the Study Eye for Patients With Non-qualified Fellow Eye and >=3 Steps Improvement on the Binocular Scale for Patients With Qualified Fellow Eyes) | 5 Participants |
| Placebo Twice Daily | Subjects With Criterion Step Improvement in DRSS at Week 48/EOT (>=2 Steps Improvement in the Study Eye for Patients With Non-qualified Fellow Eye and >=3 Steps Improvement on the Binocular Scale for Patients With Qualified Fellow Eyes) | 1 Participants |
Secondary
Subjects With Criterion Step Improvement in DRSS at Week 48/EOT (>=2 Steps Improvement in the Study Eye for Patients With Non-qualified Fellow Eye and >=3 Steps Improvement on the Person Scale for Patients With Qualified Fellow Eyes)
Subjects with Criterion Step Improvement in Diabetic Retinopathy Severity Score (DRSS) at Week 48/EOT (\>=2 Steps Improvement in the Study Eye for Patients with Non-qualified Fellow Eye and \>=3 Steps Improvement on the Person Scale for Patients with Qualified Fellow Eyes). Grading will follow Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) criteria. DRSS grades ranging from 10-85 will be converted to an ordinal score ranging from 1-11. ETDRS DRSS Level 10 = No retinopathy ETDRS DRSS Level 20 = Very mild NPDR ETDRS DRSS Level 35 = Mild NPDR ETDRS DRSS Level 43 = Moderate NPDR ETDRS DRSS Level 53 = Severe NPDR ETDRS DRSS Level 61 = Mild PDR ETDRS DRSS Level 65 = Moderate PDR ETDRS DRSS Level 71-75 = High-Risk PDR ETDRS DRSS Level 81-85 = Advanced PDR
Time frame: Treatment Period - 12 months (48 weeks)
Population: Modified Intent-to-Treat Population with at least 1 scheduled Post-Baseline Measure (LOCF)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Razuprotafib 15mg Twice Daily | Subjects With Criterion Step Improvement in DRSS at Week 48/EOT (>=2 Steps Improvement in the Study Eye for Patients With Non-qualified Fellow Eye and >=3 Steps Improvement on the Person Scale for Patients With Qualified Fellow Eyes) | 0 Participants |
| Razuprotafib 15mg Daily | Subjects With Criterion Step Improvement in DRSS at Week 48/EOT (>=2 Steps Improvement in the Study Eye for Patients With Non-qualified Fellow Eye and >=3 Steps Improvement on the Person Scale for Patients With Qualified Fellow Eyes) | 5 Participants |
| Placebo Twice Daily | Subjects With Criterion Step Improvement in DRSS at Week 48/EOT (>=2 Steps Improvement in the Study Eye for Patients With Non-qualified Fellow Eye and >=3 Steps Improvement on the Person Scale for Patients With Qualified Fellow Eyes) | 1 Participants |
Secondary
Summary of Patients Developing Center-involved DME or PDR or PDR-related Outcomes During Treatment Period Based on Clinical Data.
Summary of patients developing center-involved Diabetic Macular Edema (DME) or Proliferative Diabetic Retinopathy (PDR) or PDR-related outcomes during treatment period based on Clinical Data. Based on either clinical data or central image reading center evaluation.
Time frame: Treatment Period - 12 months (48 weeks)
Population: mITT Population With ≥1 Scheduled Post-Baseline Measure (LOCF)
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| Razuprotafib 15mg Twice Daily | Summary of Patients Developing Center-involved DME or PDR or PDR-related Outcomes During Treatment Period Based on Clinical Data. | 12 study eyes |
| Razuprotafib 15mg Daily | Summary of Patients Developing Center-involved DME or PDR or PDR-related Outcomes During Treatment Period Based on Clinical Data. | 10 study eyes |
| Placebo Twice Daily | Summary of Patients Developing Center-involved DME or PDR or PDR-related Outcomes During Treatment Period Based on Clinical Data. | 10 study eyes |
Secondary
Summary of Subjects Developing Center-involved DME or PDR or Worsening of >=2 Steps DRSS at Week 48 Based on Central Image Reading Center Evaluation
Summary of Subjects Developing Center-involved Diabetic Macular Edema (DME) or Proliferative Diabetic Retinopathy (PDR) or Worsening of \>=2 Steps Diabetic Retinopathy Severity Scale (DRSS) at Week 48 Based on Central Image Reading Center Evaluation - Study Eyes Grading will follow Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) criteria. DRSS grades ranging from 10-85 will be converted to an ordinal score ranging from 1-11. ETDRS DRSS Level 10 = No retinopathy ETDRS DRSS Level 20 = Very mild NPDR ETDRS DRSS Level 35 = Mild NPDR ETDRS DRSS Level 43 = Moderate NPDR ETDRS DRSS Level 53 = Severe NPDR ETDRS DRSS Level 61 = Mild PDR ETDRS DRSS Level 65 = Moderate PDR ETDRS DRSS Level 71-75 = High-Risk PDR ETDRS DRSS Level 81-85 = Advanced PDR
Time frame: Treatment Period - 12 months (48 weeks)
Population: Modified Intent-to-Treat Population With at Least 1 Scheduled Post-Baseline Measure (LOCF)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Razuprotafib 15mg Twice Daily | Summary of Subjects Developing Center-involved DME or PDR or Worsening of >=2 Steps DRSS at Week 48 Based on Central Image Reading Center Evaluation | 10 Participants |
| Razuprotafib 15mg Daily | Summary of Subjects Developing Center-involved DME or PDR or Worsening of >=2 Steps DRSS at Week 48 Based on Central Image Reading Center Evaluation | 8 Participants |
| Placebo Twice Daily | Summary of Subjects Developing Center-involved DME or PDR or Worsening of >=2 Steps DRSS at Week 48 Based on Central Image Reading Center Evaluation | 7 Participants |
Secondary
Summary of Subjects With an Improvement or Worsening in the Study Eye DRSS of ≥ 3 Steps at Week 48.
Summary of subjects with an improvement or worsening in the study eye Diabetic Retinopathy Severity Score (DRSS) of ≥ 3 steps at Week 48 (compared to placebo) Grading will follow Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) criteria. DRSS grades ranging from 10-85 will be converted to an ordinal score ranging from 1-11. ETDRS DRSS Level 10 = No retinopathy ETDRS DRSS Level 20 = Very mild NPDR ETDRS DRSS Level 35 = Mild NPDR ETDRS DRSS Level 43 = Moderate NPDR ETDRS DRSS Level 53 = Severe NPDR ETDRS DRSS Level 61 = Mild PDR ETDRS DRSS Level 65 = Moderate PDR ETDRS DRSS Level 71-75 = High-Risk PDR ETDRS DRSS Level 81-85 = Advanced PDR
Time frame: Baseline to Week 48
Population: The modified intent-to-treat population consisted of all enrolled subjects who received at least 1 dose of study medication and was the population used for the efficacy population.
| Arm | Measure | Group | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| Razuprotafib 15mg Twice Daily | Summary of Subjects With an Improvement or Worsening in the Study Eye DRSS of ≥ 3 Steps at Week 48. | Worsening ≥3 steps | 3 study eyes |
| Razuprotafib 15mg Twice Daily | Summary of Subjects With an Improvement or Worsening in the Study Eye DRSS of ≥ 3 Steps at Week 48. | Improvement ≥3 steps | 0 study eyes |
| Razuprotafib 15mg Daily | Summary of Subjects With an Improvement or Worsening in the Study Eye DRSS of ≥ 3 Steps at Week 48. | Worsening ≥3 steps | 4 study eyes |
| Razuprotafib 15mg Daily | Summary of Subjects With an Improvement or Worsening in the Study Eye DRSS of ≥ 3 Steps at Week 48. | Improvement ≥3 steps | 0 study eyes |
| Placebo Twice Daily | Summary of Subjects With an Improvement or Worsening in the Study Eye DRSS of ≥ 3 Steps at Week 48. | Worsening ≥3 steps | 3 study eyes |
| Placebo Twice Daily | Summary of Subjects With an Improvement or Worsening in the Study Eye DRSS of ≥ 3 Steps at Week 48. | Improvement ≥3 steps | 0 study eyes |
Secondary
Summary of Subjects With a Worsening in the Study Eye DRSS of ≥ 2 Steps at Week 48
Worsening of Diabetic Retinopathy Severity Score (DRSS) severity of ≥ 2 steps in study eyes at Week 48 (compared to placebo group) Grading will follow Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) criteria. DRSS grades ranging from 10-85 will be converted to an ordinal score ranging from 1-11. ETDRS DRSS Level 10 = No retinopathy ETDRS DRSS Level 20 = Very mild NPDR ETDRS DRSS Level 35 = Mild NPDR ETDRS DRSS Level 43 = Moderate NPDR ETDRS DRSS Level 53 = Severe NPDR ETDRS DRSS Level 61 = Mild PDR ETDRS DRSS Level 65 = Moderate PDR ETDRS DRSS Level 71-75 = High-Risk PDR ETDRS DRSS Level 81-85 = Advanced PDR
Time frame: Baseline to Week 48
Population: The modified intent-to-treat population consisted of all enrolled subjects who received at least 1 dose of study medication and was the population used for the efficacy population.
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| Razuprotafib 15mg Twice Daily | Summary of Subjects With a Worsening in the Study Eye DRSS of ≥ 2 Steps at Week 48 | 5 study eyes |
| Razuprotafib 15mg Daily | Summary of Subjects With a Worsening in the Study Eye DRSS of ≥ 2 Steps at Week 48 | 6 study eyes |
| Placebo Twice Daily | Summary of Subjects With a Worsening in the Study Eye DRSS of ≥ 2 Steps at Week 48 | 4 study eyes |