Diabetic Retinopathy
Conditions
Keywords
Diabetic Retinopathy, Ophthalmic solution, Non-proliferative diabetic retinopathy, Proliferative diabetic retinopathy
Brief summary
This study will evaluate the safety and efficacy of OTT166 Ophthalmic solution in participants with Diabetic Retinopathy.
Detailed description
This randomized, double-masked, vehicle controlled, phase 2 study will evaluate the safety and efficacy of OTT166 ophthalmic solution in participants with diabetic retinopathy and select an optimum dosing regimen for Phase 3 pivotal trials. Approximately 210 participants diagnosed with moderately severe to severe non-proliferative diabetic retinopathy (NPDR) or mild proliferative diabetic retinopathy (PDR) and who are treatment naïve (ie, no prior anti-vascular endothelial growth factor \[anti-VEGF\] or laser \[focal, grid, pan-retinal photocoagulation (PRP)\] administered) will be randomized 2:2:1:1 into the following groups: OTT166 5% twice daily (BID), OTT166 5% four times daily (QID), vehicle control BID, vehicle control QID. Randomization will be stratified by baseline Diabetic Retinopathy Severity Scale (DRSS) score (47 or 53 or 61B). Participants with PDR (DRSS score 61B) will be capped at 20% of all randomized participants. Each group will self-administer one 50-μl eye drop of study solution (frequency as assigned) for 24 weeks.
Interventions
DRUGOTT166
Participants will receive OTT166 ophthalmic solution
DRUGVehicle control
Participants will receive vehicle control
Sponsors
Parexel
OcuTerra Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Men or women ≥ 18 years of age with type 1 or 2 diabetes mellitus who have moderately severe to severe NPDR \[DRSS levels 47 or 53\], or mild PDR \[DRSS level 61\] NVE \< 0.5 DA in 1 + quadrants\], in whom PRP and/or anti-VEGF IVT can be safely deferred for at least 6 months per the Investigator 2. BCVA ETDRS letter score in the study eye of ≥ 69 letters (approximate Snellen equivalent of 20/40 or better) 3. Normal foveal contour 4. Treatment naïve (ie, no previous anti-VEGF or steroid treatment or PRP or laser) 5. Willing and able to return for all study visits and comply with study-related procedures 6. Able to adhere to the study dosing requirements 7. Understands and signs the written Informed Consent Form
Exclusion criteria
1. CST of \> 325 μm a. Fluid in the central subfield is allowed so long as CST is ≤325 μm and there is a normal foveal contour as determined by the Central Reading Center 2. Any prior focal or grid laser photocoagulation or any prior PRP in the study eye as it pertains to treatment of DME or DR (peripheral retinal hole treated with laser is allowed) 3. Eyes with DRSS score 61 with fibrous proliferations at disc or fibrous proliferations elsewhere a. DRSS score 61B with NVE only is allowed. Any sign of fibrosis proliferation is exclusionary 4. Any prior systemic anti-VEGF treatment or IVT anti-VEGF treatment in the study eye 5. Any prior intraocular steroid injection in the study eye, inclusive of Iluvien® and Retisert® a. History of Ozurdex® and triamcinolone use prior to 12 months before study enrollment is allowed 6. Current ASNV, vitreous hemorrhage, or tractional retinal detachment visible at the screening assessments in the study eye 7. Uncontrolled glaucoma or ocular hypertension in the study eye defined as an IOP \> 25 mmHg regardless of concomitant treatment with IOP-lowering medications 8. Hypertension defined as systolic \> 180 mmHg or \> 160 mmHg on 2 consecutive measurements (during the same visit) or diastolic \> 100 mmHg 9. Screening HbA1c blood test \> 12.0% 10. Renal failure (stage 4 or end-stage), dialysis, or history of renal transplant 11. History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect interpretation of the results of the study or render the participant at high risk for treatment complications 12. Initiation of intensive insulin treatment (a pump or multiple daily injections) within 4 months prior to randomization or plans to do so in the next 4 months 13. Epiretinal membrane, posterior hyaloidal traction, and/or vitreomacular traction in the study eye as determined to be significant by the Investigator 14. Previous pars plana vitrectomy in the study eye 15. Any intraocular surgery in the study eye within 90 days (3 months) prior to study enrollment 16. YAG laser treatment in the study eye within 90 days prior to study enrollment 17. Concomitant use of any topical ophthalmic medications in the study eye, including dry eye or glaucoma medications, unless on a stable dose for at least 90 days prior to study enrollment and expected to stay on stable dose throughout study participation. Topical eyedrops are allowed but not within ±10 minutes of study drop application 18. Contact lens use from time of screening throughout the study 19. Central corneal changes from dry eye that are visually significant and/or Sjogren's syndrome 20. Visually significant Fuchs endothelial dystrophy or other diagnosed conditions of corneal compromise including Anterior Basement Membrane Dystrophy, or any corneal dystrophy affecting central vision (peripheral processes are not exclusionary) 21. Chronic or recurrent uveitis in the study eye 22. Ongoing ocular infection or inflammation in either eye 23. A history of cataract surgery complicated by vitreous loss in the study eye 24. Congenital eye malformations in the study eye 25. A history of penetrating ocular trauma in the study eye 26. Cognitive impairment that, in the opinion of the investigator, could compromise compliance with the requirements of the study 27. Females of childbearing potential (ie, who are not postmenopausal for at least 1 year or surgically sterile for at least 6 weeks prior to Visit 1 - Screening/Randomization) who are lactating, or who are pregnant as determined by a positive serum pregnancy test at Visit 1 -Screening/Randomization. Women of childbearing potential must agree to use acceptable methods of birth control throughout the study a. Women who are breastfeeding or who have a positive serum hCG/urine pregnancy test at the screening or BL Visit 28. Females and males of childbearing potential unwilling or unable to utilize the following acceptable methods of birth control: tubal ligation, transdermal patch, intrauterine devices/systems, oral/implantable/injectable or contraceptives, diaphragm or cervical cap with spermicide, or vasectomized partner for females; condoms with spermicidal agent and vasectomy for males; or sexual abstinence for males and females 29. Participation in any other investigational device or drug clinical research study within 12 weeks of Visit 1 - Screening/Randomization and during the duration of enrollment 30. Contraindication to the study medications or fluorescein dye 31. Other ocular pathologies that, in the investigator's opinion, would interfere with the participant's vision in the study eye 32. Ocular media of insufficient quality to obtain fundus photographs, fluorescein angiography, and OCT images in the study eye 33. Concomitant use of Semaglutide (Wegovy®, Ozempic®, Rybelsus®), Thiazolidinediones (Actos®, Avandia®), Liraglutides (Victoza®, Saxenda®), Dulaglutide (Trulicity®), or Tirzepatide (Mounjaro®) within 12 months prior to Visit 1 (allowed if a stable dose has been established for at least 1 year of use) a. Plans to start concomitant use of Semaglutide or Thiazolidinediones during the study duration is exclusionary
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Who Improved by ≥ 2 Steps From Baseline in Diabetic Retinopathy Severity Scale (DRSS) Scores | At week 24 | To characterize the efficacy of topical OTT166 in participants with DR, the Diabetic Retinopathy Severity Scale (DRSS) was used. The DRSS ranges from 10 to 85 in 12 discrete steps with higher score representing worse DR. The DRSS values were determined by the central reading center. The data reported are the estimated percentage of participants that improved by at least 2 steps from baseline. The reported data include the use of imputation according to the primary estimand as described in the protocol. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants That Developed Worse Than Mild PDR (DRSS 65 and Above) | At week 24 | To determine if topical OTT166 prevented or delayed the occurrence of worse than mild PDR, DRSS of 65 and above. The higher the DRSS, the greater the risk of vision loss and thus the standard of care is to treat affected patients aggressively. The reported data include the use of imputation according to the primary estimand as described in the protocol. |
| Proportion of Participants Who Developed ASNV | At week 24 | To determine if topical OTT166 prevented or delayed the occurrence of anterior segment neovascularization (ASNV). Measure is the percentage of patients that developed ASNV at 24 weeks. The reported data include the use of imputation according to the primary estimand as described in the protocol. |
| Development of PDR Worse Than Mild (Wtm) (DRSS 65 and Above) | At week 24 | To determine if topical OTT166 prevented or delayed the occurrence of worse than mild PDR (wtmPDR). The determination was made using Kaplan-Meier methodology. The estimated percentage that progressed to wtmPDR by Week 24 is reported. The reported data include the use of imputation according to the primary estimand as described in the protocol. |
| Proportion of Participants Who Developed CI-DME | At week 24 | To determine if topical OTT166 prevented or delayed the occurrence of CI-DME. CI-DME is defined as the presence of fluid in the central subfield in participants who have no fluid at baseline or CST\> 325 μm. The reported data include the use of imputation according to the primary estimand as described in the protocol. |
| The Development of CI-DME | At week 24 | To determine if topical OTT166 prevented or delayed the occurrence of CI-DME. CI-DME is defined as the presence of fluid in the central subfield in participants who have no fluid at baseline or CST\> 325 μm. The reported data include the use of imputation according to the primary estimand as described in the protocol. The percentages of participants that developed CI-DME at Week 24 are reported. |
| Proportion of Participants That Developed Visually Threatening Complications (VTC) Complications (VTC) | At Week 24 | To determine if topical OTT166 prevented or delayed the occurrence of a VTC. VTC is defined as the composite outcome of PDR and/or ASNV and/or CI-DME. |
| Time to Development of PDR Worse Than Mild (DRSS 65 and Above) or CI-DME | From Baseline (Day 1) up to Week 24 | To determine if topical OTT166 prevented or delayed the occurrence of PDR worse than mild (DRSS 65 and above) or CI-DME. CI-DME is defined as the presence of fluid in the central subfield in participants who have no fluid at baseline or CST\> 325 μm. Participants who experienced one or more events (worse than mild PDR and/or CI-DME), the earliest event date was selected. Participants who did not experience either event were censored at the earliest of the last available assessment. Median time to event is reported if calculable. |
| Proportion of Participants With Change in DRSS Steps at Week 24 Compared to Baseline | At week 24 | To determine the effect of OTT166 on DRSS in participants with moderately severe to severe NPDR and mild PDR treated with topical OTT166. Change in DRSS steps is defined as DR worsening or improving by 1, 2, or ≥ 3 steps along with no change. The reported data include the use of imputation according to the primary estimand as described in the protocol. |
| Proportion of Participants With Mild PDR at Baseline Who Regressed to NPDR | At week 24 | To determine the effect of OTT166 on DRSS in participants with mild PDR (DRSS 61B) treated with topical OTT166. Regression of disease was defined as decrease in DRSS to 53 or lower. The reported data include the use of imputation according to the primary estimand as described in the protocol. |
| Proportion That Met Objective Rescue Therapy Criteria by Week 24 | From Baseline (Day 1) up to Week 24 | To determine the effect of OTT166 on the need for rescue therapy in participants with moderately severe to severe NPDR and mild PDR. The reported data include the use of imputation according to the primary estimand as described in the protocol. |
| Percentages of Participants at Week 24 That Had Had Rescue Therapy Administered | 24 Weeks | To determine the impact of treatment with OTT166 on the time to receiving rescue therapy. Analysis was performed using the Kaplan-Meier methodology. The reported data include the use of imputation according to the primary estimand as described in the protocol. The data reported are the estimated percentages of participants at Week 24 that had had rescue therapy administered. |
| Change From Baseline in Best Corrected Visual Acuity (BCVA) | From Baseline (Day 1) up to Week 24 | To determine the effect of OTT166 on BCVA in participants with moderately severe to severe NPDR and mild PDR. BCVA was assessed by Early Treatment Diabetic Retinopathy Study (ETDRS) letters score. A higher score represents better visual function. |
| Proportion of Participants With Lines Gained/Lost of BCVA | From Baseline (Day 1) up to Week 24 | To determine the effect of OTT166 on BCVA in participants with moderately severe to severe NPDR and mild PDR. Proportion of participants who gained/lost lines of BCVA (± 5, 10, and 15 ETDRS letters) were assessed. The reported data include the use of imputation according to the primary estimand as described in the protocol. 5 ETDRS letters = 1 line. |
| Area Under the Curve for BCVA (ETDRS Letters) From Baseline to Week 24 | From Baseline (Day 1) up to Week 24 | To determine the effect of OTT166 on BCVA in participants with moderately severe to severe NPDR and mild PDR. BCVA was assessed by ETDRS letters score. A higher score represents better functioning. AUC from baseline to 24 weeks is calculated by the linear trapezoidal method. |
| Change From Baseline in Central Subfield Thickness (CST) | From Baseline (Day 1) up to Week 24 | To determine the effect of OTT166 on CST in participants with moderately severe to severe NPDR and mild PDR. CST was measured by optical coherence tomography (OCT). |
| Area Under The Curve (AUC) for Change From Baseline in CST | From Baseline (Day 1) up to Week 24 | To determine the effect of OTT166 on CST in participants with moderately severe to severe NPDR and mild PDR. CST was measured by OCT. |
| Proportion of Participants Who Met the Objective Rescue Criteria | From Baseline (Day 1) up to Week 24 | To determine the effect of OTT166 on the need for rescue therapy in participants with moderately severe to severe NPDR and mild PDR. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants That Develop a VTC by Week 24 for DRSS Levels 47 and 53 at Baseline | 24 weeks | A pre-specified sub group analysis of the NPDR population (DRSS 47 or 53) for the development of a VTC defined as worse than mild PDR, CI-DME or ASNV. The reported data include the use of imputation according to the primary estimand as described in the protocol. |
| Proportion of Participants Who Developed CI-DME at Week 24 for Randomization Strata DRSS 47 and 53 | 24 weeks | A measure of the ability to prevent CI-DME in participants with NPDR treated with OTT166. The proportion of patients that develop CI-DME (defined as new fluid in patients with no fluid at baseline or CST \> 325 microns) by week 24. This is a pre-specified sub group analysis and excludes the participants in the DRSS 61B stratum. The reported data include the use of imputation according to the primary estimand as described in the protocol. |
Countries
Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| OTT166 Cohort 1 Participants received OTT166 low dose for 24 weeks
OTT166: Participants received OTT166 5% ophthalmic solution twice a day for 24 weeks | 75 |
| OTT166 Cohort 2 Participants received OTT166 high dose for 24 weeks
OTT166: Participants received OTT166 5% ophthalmic solution four times a day for 24 weeks | 76 |
| Vehicle Control Cohort 1 Participants received vehicle control for 24 weeks
Vehicle control: Participants received vehicle control twice a day for 24 weeks | 38 |
| Vehicle Control Cohort 2 Participants received vehicle control for 24 weeks
Vehicle control: Participants received vehicle control four times a day for 24 weeks | 36 |
| Total | 225 |
Baseline characteristics
| Characteristic | Vehicle Control Cohort 1 | OTT166 Cohort 1 | OTT166 Cohort 2 | Vehicle Control Cohort 2 | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 13 Participants | 21 Participants | 19 Participants | 8 Participants | 61 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants | 54 Participants | 57 Participants | 28 Participants | 164 Participants |
| Age, Continuous | 57.7 years | 56.7 years | 56.8 years | 53.9 years | 56.4 years |
| Best corrected visual acuity | 82.9 letters | 82.8 letters | 82.6 letters | 83.4 letters | 82.9 letters |
| Body mass index | 33.2 kg/m^2 | 34.1 kg/m^2 | 33.4 kg/m^2 | 34.1 kg/m^2 | 34.1 kg/m^2 |
| Central subfield thickness (CST) | 262.01 microns | 252.18 microns | 260.72 microns | 256.53 microns | 257.42 microns |
| Diabetic retinopathy Severity Scale at Screening DRSS 47 | 23 participants | 47 participants | 46 participants | 23 participants | 139 participants |
| Diabetic retinopathy Severity Scale at Screening DRSS 53 | 7 participants | 13 participants | 14 participants | 6 participants | 40 participants |
| Diabetic retinopathy Severity Scale at Screening DRSS 61B | 8 participants | 15 participants | 16 participants | 7 participants | 46 participants |
| Duration of Diabetic Retinopathy | 2.667 years | 1.699 years | 1.896 years | 1.166 years | 1.843 years |
| Hemoglobin a1c | 8.37 % of RBCs with glycosylated hemoglobin | 8.56 % of RBCs with glycosylated hemoglobin | 8.50 % of RBCs with glycosylated hemoglobin | 8.64 % of RBCs with glycosylated hemoglobin | 8.52 % of RBCs with glycosylated hemoglobin |
| Race/Ethnicity, Customized Asian | 3 Participants | 4 Participants | 2 Participants | 2 Participants | 11 Participants |
| Race/Ethnicity, Customized Black or African American | 3 Participants | 12 Participants | 6 Participants | 3 Participants | 24 Participants |
| Race/Ethnicity, Customized Not reported | 0 Participants | 3 Participants | 0 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized White | 31 Participants | 55 Participants | 66 Participants | 30 Participants | 182 Participants |
| Sex: Female, Male Female | 13 Participants | 38 Participants | 32 Participants | 12 Participants | 95 Participants |
| Sex: Female, Male Male | 25 Participants | 37 Participants | 44 Participants | 24 Participants | 130 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 75 | 0 / 76 | 0 / 38 | 0 / 36 |
| other Total, other adverse events | 36 / 75 | 35 / 76 | 13 / 38 | 17 / 36 |
| serious Total, serious adverse events | 6 / 75 | 6 / 76 | 1 / 38 | 5 / 36 |
Outcome results
Primary
Proportion of Participants Who Improved by ≥ 2 Steps From Baseline in Diabetic Retinopathy Severity Scale (DRSS) Scores
To characterize the efficacy of topical OTT166 in participants with DR, the Diabetic Retinopathy Severity Scale (DRSS) was used. The DRSS ranges from 10 to 85 in 12 discrete steps with higher score representing worse DR. The DRSS values were determined by the central reading center. The data reported are the estimated percentage of participants that improved by at least 2 steps from baseline. The reported data include the use of imputation according to the primary estimand as described in the protocol.
Time frame: At week 24
Population: All participants randomized received at least one dose of study drug which is the Intent to Treat (ITT) population for the study. As was pre-specified in the study protocol, all participants assigned to receive vehicle control are reported as a single Arm/Group, Vehicle Control Combined.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OTT166 Cohort 1 | Proportion of Participants Who Improved by ≥ 2 Steps From Baseline in Diabetic Retinopathy Severity Scale (DRSS) Scores | 12.187 estimated improvement percentage |
| OTT166 Cohort 2 | Proportion of Participants Who Improved by ≥ 2 Steps From Baseline in Diabetic Retinopathy Severity Scale (DRSS) Scores | 12.263 estimated improvement percentage |
| Vehicle Control Combined | Proportion of Participants Who Improved by ≥ 2 Steps From Baseline in Diabetic Retinopathy Severity Scale (DRSS) Scores | 13.311 estimated improvement percentage |
Comparison: The study was powered to provide a 90% probability to detect a 20% difference between each treatment arm and the combined vehicle control.p-value: 0.57390% CI: [-10.578, 8.449]Mantel Haenszel
p-value: 0.57590% CI: [-11.178, 8.874]Mantel Haenszel
Secondary
Area Under The Curve (AUC) for Change From Baseline in CST
To determine the effect of OTT166 on CST in participants with moderately severe to severe NPDR and mild PDR. CST was measured by OCT.
Time frame: From Baseline (Day 1) up to Week 24
Population: ITT population. As was pre-specified in the study protocol, all participants assigned to receive vehicle control are reported as a single Arm/Group, Vehicle Control Combined.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| OTT166 Cohort 1 | Area Under The Curve (AUC) for Change From Baseline in CST | 6.308 microns*day | Standard Error 0.0568 |
| OTT166 Cohort 2 | Area Under The Curve (AUC) for Change From Baseline in CST | 6.296 microns*day | Standard Error 0.0561 |
| Vehicle Control Combined | Area Under The Curve (AUC) for Change From Baseline in CST | 6.287 microns*day | Standard Error 0.0567 |
p-value: 0.60690% CI: [-0.1043, 0.1452]ANCOVA
p-value: 0.54490% CI: [-0.1161, 0.1326]ANCOVA
Secondary
Area Under the Curve for BCVA (ETDRS Letters) From Baseline to Week 24
To determine the effect of OTT166 on BCVA in participants with moderately severe to severe NPDR and mild PDR. BCVA was assessed by ETDRS letters score. A higher score represents better functioning. AUC from baseline to 24 weeks is calculated by the linear trapezoidal method.
Time frame: From Baseline (Day 1) up to Week 24
Population: ITT population. As was pre-specified in the study protocol, all participants assigned to receive vehicle control are reported as a single Arm/Group, Vehicle Control Combined.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| OTT166 Cohort 1 | Area Under the Curve for BCVA (ETDRS Letters) From Baseline to Week 24 | 1997.9673 letters*day | Standard Error 19.3899 |
| OTT166 Cohort 2 | Area Under the Curve for BCVA (ETDRS Letters) From Baseline to Week 24 | 1977.5682 letters*day | Standard Error 19.1258 |
| Vehicle Control Combined | Area Under the Curve for BCVA (ETDRS Letters) From Baseline to Week 24 | 1993.8143 letters*day | Standard Error 19.4706 |
p-value: 0.43790% CI: [-38.793, 47.0991]ANCOVA
p-value: 0.73390% CI: [-59.2538, 26.7616]ANCOVA
Secondary
Change From Baseline in Best Corrected Visual Acuity (BCVA)
To determine the effect of OTT166 on BCVA in participants with moderately severe to severe NPDR and mild PDR. BCVA was assessed by Early Treatment Diabetic Retinopathy Study (ETDRS) letters score. A higher score represents better visual function.
Time frame: From Baseline (Day 1) up to Week 24
Population: ITT population. As was pre-specified in the study protocol, all participants assigned to receive vehicle control are reported as a single Arm/Group, Vehicle Control Combined.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| OTT166 Cohort 1 | Change From Baseline in Best Corrected Visual Acuity (BCVA) | -0.5829 ETDRS letters | Standard Error 1.053 |
| OTT166 Cohort 2 | Change From Baseline in Best Corrected Visual Acuity (BCVA) | -2.3353 ETDRS letters | Standard Error 1.0647 |
| Vehicle Control Combined | Change From Baseline in Best Corrected Visual Acuity (BCVA) | -0.0504 ETDRS letters | Standard Error 1.0594 |
p-value: 0.64790% CI: [-2.8478, 1.7827]ANCOVA
p-value: 0.94590% CI: [-4.6356, 0.0658]ANCOVA
Secondary
Change From Baseline in Central Subfield Thickness (CST)
To determine the effect of OTT166 on CST in participants with moderately severe to severe NPDR and mild PDR. CST was measured by optical coherence tomography (OCT).
Time frame: From Baseline (Day 1) up to Week 24
Population: ITT population. As was pre-specified in the study protocol, all participants assigned to receive vehicle control are reported as a single Arm/Group, Vehicle Control Combined.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| OTT166 Cohort 1 | Change From Baseline in Central Subfield Thickness (CST) | 14.479 microns | Standard Error 4.0974 |
| OTT166 Cohort 2 | Change From Baseline in Central Subfield Thickness (CST) | 9.365 microns | Standard Error 4.102 |
| Vehicle Control Combined | Change From Baseline in Central Subfield Thickness (CST) | 10.416 microns | Standard Error 4.1107 |
p-value: 0.7790% CI: [-4.9712, 13.098]ANCOVA
p-value: 0.42490% CI: [-10.1046, 8.0032]ANCOVA
Secondary
Development of PDR Worse Than Mild (Wtm) (DRSS 65 and Above)
To determine if topical OTT166 prevented or delayed the occurrence of worse than mild PDR (wtmPDR). The determination was made using Kaplan-Meier methodology. The estimated percentage that progressed to wtmPDR by Week 24 is reported. The reported data include the use of imputation according to the primary estimand as described in the protocol.
Time frame: At week 24
Population: ITT Population. As was pre-specified in the study protocol, all participants assigned to receive vehicle control are reported as a single Arm/Group, Vehicle Control Combined.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OTT166 Cohort 1 | Development of PDR Worse Than Mild (Wtm) (DRSS 65 and Above) | 13 percentage of participants |
| OTT166 Cohort 2 | Development of PDR Worse Than Mild (Wtm) (DRSS 65 and Above) | 17 percentage of participants |
| Vehicle Control Combined | Development of PDR Worse Than Mild (Wtm) (DRSS 65 and Above) | 16 percentage of participants |
p-value: 0.39790% CI: [0.4378, 1.8467]Log Rank
p-value: 0.60590% CI: [0.5596, 2.2117]Log Rank
Secondary
Percentages of Participants at Week 24 That Had Had Rescue Therapy Administered
To determine the impact of treatment with OTT166 on the time to receiving rescue therapy. Analysis was performed using the Kaplan-Meier methodology. The reported data include the use of imputation according to the primary estimand as described in the protocol. The data reported are the estimated percentages of participants at Week 24 that had had rescue therapy administered.
Time frame: 24 Weeks
Population: ITT population. As was pre-specified in the study protocol, all participants assigned to receive vehicle control are reported as a single Arm/Group, Vehicle Control Combined.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OTT166 Cohort 1 | Percentages of Participants at Week 24 That Had Had Rescue Therapy Administered | 4 estimated percentage of participants |
| OTT166 Cohort 2 | Percentages of Participants at Week 24 That Had Had Rescue Therapy Administered | 6 estimated percentage of participants |
| Vehicle Control Combined | Percentages of Participants at Week 24 That Had Had Rescue Therapy Administered | 4 estimated percentage of participants |
p-value: 0.47890% CI: [0.2473, 3.6295]Log Rank
p-value: 0.63190% CI: [0.3688, 4.5512]Log Rank
Secondary
Proportion of Participants That Developed Visually Threatening Complications (VTC) Complications (VTC)
To determine if topical OTT166 prevented or delayed the occurrence of a VTC. VTC is defined as the composite outcome of PDR and/or ASNV and/or CI-DME.
Time frame: At Week 24
Population: ITT population. As was pre-specified in the study protocol, all participants assigned to receive vehicle control are reported as a single Arm/Group, Vehicle Control Combined.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OTT166 Cohort 1 | Proportion of Participants That Developed Visually Threatening Complications (VTC) Complications (VTC) | 23.387 estimated risk percentage |
| OTT166 Cohort 2 | Proportion of Participants That Developed Visually Threatening Complications (VTC) Complications (VTC) | 28.829 estimated risk percentage |
| Vehicle Control Combined | Proportion of Participants That Developed Visually Threatening Complications (VTC) Complications (VTC) | 29.838 estimated risk percentage |
p-value: 0.202290% CI: [-18.994, 6.215]Mantel Haenszel
p-value: 0.447690% CI: [-14.07, 11.984]Mantel Haenszel
Secondary
Proportion of Participants That Developed Worse Than Mild PDR (DRSS 65 and Above)
To determine if topical OTT166 prevented or delayed the occurrence of worse than mild PDR, DRSS of 65 and above. The higher the DRSS, the greater the risk of vision loss and thus the standard of care is to treat affected patients aggressively. The reported data include the use of imputation according to the primary estimand as described in the protocol.
Time frame: At week 24
Population: ITT population. As was pre-specified in the study protocol, all participants assigned to receive vehicle control are reported as a single Arm/Group, Vehicle Control Combined.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OTT166 Cohort 1 | Proportion of Participants That Developed Worse Than Mild PDR (DRSS 65 and Above) | 12.467 estimated risk percentage |
| OTT166 Cohort 2 | Proportion of Participants That Developed Worse Than Mild PDR (DRSS 65 and Above) | 15.316 estimated risk percentage |
| Vehicle Control Combined | Proportion of Participants That Developed Worse Than Mild PDR (DRSS 65 and Above) | 9.405 estimated risk percentage |
p-value: 0.727690% CI: [-5.314, 11.592]Mantel Haenszel
p-value: 0.849290% CI: [-3.424, 14.982]Mantel Haenszel
Secondary
Proportion of Participants Who Developed ASNV
To determine if topical OTT166 prevented or delayed the occurrence of anterior segment neovascularization (ASNV). Measure is the percentage of patients that developed ASNV at 24 weeks. The reported data include the use of imputation according to the primary estimand as described in the protocol.
Time frame: At week 24
Population: ITT population. As was pre-specified in the study protocol, all participants assigned to receive vehicle control are reported as a single Arm/Group, Vehicle Control Combined.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OTT166 Cohort 1 | Proportion of Participants Who Developed ASNV | 4.200 estimated risk percentage |
| OTT166 Cohort 2 | Proportion of Participants Who Developed ASNV | 4.487 estimated risk percentage |
| Vehicle Control Combined | Proportion of Participants Who Developed ASNV | 6.068 estimated risk percentage |
p-value: 0.309790% CI: [-8.036, 4.309]Mantel Haenszel
p-value: 0.341490% CI: [-8.021, 4.829]Mantel Haenszel
Secondary
Proportion of Participants Who Developed CI-DME
To determine if topical OTT166 prevented or delayed the occurrence of CI-DME. CI-DME is defined as the presence of fluid in the central subfield in participants who have no fluid at baseline or CST\> 325 μm. The reported data include the use of imputation according to the primary estimand as described in the protocol.
Time frame: At week 24
Population: ITT population. As was pre-specified in the study protocol, all participants assigned to receive vehicle control are reported as a single Arm/Group, Vehicle Control Combined.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OTT166 Cohort 1 | Proportion of Participants Who Developed CI-DME | 14.827 estimated risk percentage |
| OTT166 Cohort 2 | Proportion of Participants Who Developed CI-DME | 20.513 estimated risk percentage |
| Vehicle Control Combined | Proportion of Participants Who Developed CI-DME | 25.459 estimated risk percentage |
p-value: 0.061990% CI: [-21.972, 0.728]Mantel Haenszel
p-value: 0.248390% CI: [-16.897, 7.013]Mantel Haenszel
Secondary
Proportion of Participants Who Met the Objective Rescue Criteria
To determine the effect of OTT166 on the need for rescue therapy in participants with moderately severe to severe NPDR and mild PDR.
Time frame: From Baseline (Day 1) up to Week 24
Population: ITT population. As was pre-specified in the study protocol, all participants assigned to receive vehicle control are reported as a single Arm/Group, Vehicle Control Combined.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OTT166 Cohort 1 | Proportion of Participants Who Met the Objective Rescue Criteria | 20.000 estimated percentage |
| OTT166 Cohort 2 | Proportion of Participants Who Met the Objective Rescue Criteria | 23.684 estimated percentage |
| Vehicle Control Combined | Proportion of Participants Who Met the Objective Rescue Criteria | 21.622 estimated percentage |
p-value: 0.40690% CI: [-12.247, 9.158]Mantel Haenszel
p-value: 0.60590% CI: [-9.114, 12.64]Mantel Haenszel
Secondary
Proportion of Participants With Change in DRSS Steps at Week 24 Compared to Baseline
To determine the effect of OTT166 on DRSS in participants with moderately severe to severe NPDR and mild PDR treated with topical OTT166. Change in DRSS steps is defined as DR worsening or improving by 1, 2, or ≥ 3 steps along with no change. The reported data include the use of imputation according to the primary estimand as described in the protocol.
Time frame: At week 24
Population: ITT population. As was pre-specified in the study protocol, all participants assigned to receive vehicle control are reported as a single Arm/Group, Vehicle Control Combined.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| OTT166 Cohort 1 | Proportion of Participants With Change in DRSS Steps at Week 24 Compared to Baseline | Improved by ≥3 steps | 4.0 percentage of participants |
| OTT166 Cohort 1 | Proportion of Participants With Change in DRSS Steps at Week 24 Compared to Baseline | Improved by 2 steps | 8.0 percentage of participants |
| OTT166 Cohort 1 | Proportion of Participants With Change in DRSS Steps at Week 24 Compared to Baseline | Improved by 1 step | 18.7 percentage of participants |
| OTT166 Cohort 1 | Proportion of Participants With Change in DRSS Steps at Week 24 Compared to Baseline | No change | 44.0 percentage of participants |
| OTT166 Cohort 1 | Proportion of Participants With Change in DRSS Steps at Week 24 Compared to Baseline | Worsened by 1 step | 6.7 percentage of participants |
| OTT166 Cohort 1 | Proportion of Participants With Change in DRSS Steps at Week 24 Compared to Baseline | Worsened by 2 steps | 6.7 percentage of participants |
| OTT166 Cohort 1 | Proportion of Participants With Change in DRSS Steps at Week 24 Compared to Baseline | Worsened by ≥3 steps | 1.3 percentage of participants |
| OTT166 Cohort 1 | Proportion of Participants With Change in DRSS Steps at Week 24 Compared to Baseline | missing | 10.7 percentage of participants |
| OTT166 Cohort 2 | Proportion of Participants With Change in DRSS Steps at Week 24 Compared to Baseline | Improved by 1 step | 17.1 percentage of participants |
| OTT166 Cohort 2 | Proportion of Participants With Change in DRSS Steps at Week 24 Compared to Baseline | Worsened by ≥3 steps | 5.3 percentage of participants |
| OTT166 Cohort 2 | Proportion of Participants With Change in DRSS Steps at Week 24 Compared to Baseline | No change | 36.8 percentage of participants |
| OTT166 Cohort 2 | Proportion of Participants With Change in DRSS Steps at Week 24 Compared to Baseline | Worsened by 1 step | 5.3 percentage of participants |
| OTT166 Cohort 2 | Proportion of Participants With Change in DRSS Steps at Week 24 Compared to Baseline | Worsened by 2 steps | 2.6 percentage of participants |
| OTT166 Cohort 2 | Proportion of Participants With Change in DRSS Steps at Week 24 Compared to Baseline | Improved by ≥3 steps | 1.3 percentage of participants |
| OTT166 Cohort 2 | Proportion of Participants With Change in DRSS Steps at Week 24 Compared to Baseline | Improved by 2 steps | 7.9 percentage of participants |
| OTT166 Cohort 2 | Proportion of Participants With Change in DRSS Steps at Week 24 Compared to Baseline | missing | 23.7 percentage of participants |
| Vehicle Control Combined | Proportion of Participants With Change in DRSS Steps at Week 24 Compared to Baseline | Improved by 1 step | 27.0 percentage of participants |
| Vehicle Control Combined | Proportion of Participants With Change in DRSS Steps at Week 24 Compared to Baseline | Improved by 2 steps | 4.1 percentage of participants |
| Vehicle Control Combined | Proportion of Participants With Change in DRSS Steps at Week 24 Compared to Baseline | Improved by ≥3 steps | 6.8 percentage of participants |
| Vehicle Control Combined | Proportion of Participants With Change in DRSS Steps at Week 24 Compared to Baseline | No change | 29.7 percentage of participants |
| Vehicle Control Combined | Proportion of Participants With Change in DRSS Steps at Week 24 Compared to Baseline | Worsened by ≥3 steps | 2.7 percentage of participants |
| Vehicle Control Combined | Proportion of Participants With Change in DRSS Steps at Week 24 Compared to Baseline | Worsened by 2 steps | 1.4 percentage of participants |
| Vehicle Control Combined | Proportion of Participants With Change in DRSS Steps at Week 24 Compared to Baseline | Worsened by 1 step | 8.1 percentage of participants |
| Vehicle Control Combined | Proportion of Participants With Change in DRSS Steps at Week 24 Compared to Baseline | missing | 20.3 percentage of participants |
p-value: 0.42890% CI: [0.4573, 2.657]odds ratio
p-value: 0.41990% CI: [0.45, 2.7846]odds ratio
Secondary
Proportion of Participants With Lines Gained/Lost of BCVA
To determine the effect of OTT166 on BCVA in participants with moderately severe to severe NPDR and mild PDR. Proportion of participants who gained/lost lines of BCVA (± 5, 10, and 15 ETDRS letters) were assessed. The reported data include the use of imputation according to the primary estimand as described in the protocol. 5 ETDRS letters = 1 line.
Time frame: From Baseline (Day 1) up to Week 24
Population: ITT population. As was pre-specified in the study protocol, all participants assigned to receive vehicle control are reported as a single Arm/Group, Vehicle Control Combined.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| OTT166 Cohort 1 | Proportion of Participants With Lines Gained/Lost of BCVA | >=15 letter gain | 0 percentage of participants |
| OTT166 Cohort 1 | Proportion of Participants With Lines Gained/Lost of BCVA | 10-14 letter gain | 2.7 percentage of participants |
| OTT166 Cohort 1 | Proportion of Participants With Lines Gained/Lost of BCVA | 5-9 letter gain | 20.0 percentage of participants |
| OTT166 Cohort 1 | Proportion of Participants With Lines Gained/Lost of BCVA | 1-4 letter gain | 30.7 percentage of participants |
| OTT166 Cohort 1 | Proportion of Participants With Lines Gained/Lost of BCVA | 0 letter loss or gain | 8.0 percentage of participants |
| OTT166 Cohort 1 | Proportion of Participants With Lines Gained/Lost of BCVA | 1-4 letter loss | 21.3 percentage of participants |
| OTT166 Cohort 1 | Proportion of Participants With Lines Gained/Lost of BCVA | 5-9 letter loss | 4.0 percentage of participants |
| OTT166 Cohort 1 | Proportion of Participants With Lines Gained/Lost of BCVA | 10-14 letter loss | 1.3 percentage of participants |
| OTT166 Cohort 1 | Proportion of Participants With Lines Gained/Lost of BCVA | >=15 letter loss | 1.3 percentage of participants |
| OTT166 Cohort 1 | Proportion of Participants With Lines Gained/Lost of BCVA | missing | 10.7 percentage of participants |
| OTT166 Cohort 2 | Proportion of Participants With Lines Gained/Lost of BCVA | >=15 letter loss | 2.6 percentage of participants |
| OTT166 Cohort 2 | Proportion of Participants With Lines Gained/Lost of BCVA | >=15 letter gain | 0 percentage of participants |
| OTT166 Cohort 2 | Proportion of Participants With Lines Gained/Lost of BCVA | 1-4 letter loss | 13.2 percentage of participants |
| OTT166 Cohort 2 | Proportion of Participants With Lines Gained/Lost of BCVA | 0 letter loss or gain | 13.2 percentage of participants |
| OTT166 Cohort 2 | Proportion of Participants With Lines Gained/Lost of BCVA | 10-14 letter gain | 1.3 percentage of participants |
| OTT166 Cohort 2 | Proportion of Participants With Lines Gained/Lost of BCVA | missing | 18.4 percentage of participants |
| OTT166 Cohort 2 | Proportion of Participants With Lines Gained/Lost of BCVA | 10-14 letter loss | 2.6 percentage of participants |
| OTT166 Cohort 2 | Proportion of Participants With Lines Gained/Lost of BCVA | 5-9 letter gain | 9.2 percentage of participants |
| OTT166 Cohort 2 | Proportion of Participants With Lines Gained/Lost of BCVA | 5-9 letter loss | 9.2 percentage of participants |
| OTT166 Cohort 2 | Proportion of Participants With Lines Gained/Lost of BCVA | 1-4 letter gain | 30.3 percentage of participants |
| Vehicle Control Combined | Proportion of Participants With Lines Gained/Lost of BCVA | 10-14 letter loss | 1.4 percentage of participants |
| Vehicle Control Combined | Proportion of Participants With Lines Gained/Lost of BCVA | 1-4 letter gain | 27.0 percentage of participants |
| Vehicle Control Combined | Proportion of Participants With Lines Gained/Lost of BCVA | 0 letter loss or gain | 5.4 percentage of participants |
| Vehicle Control Combined | Proportion of Participants With Lines Gained/Lost of BCVA | 1-4 letter loss | 23.0 percentage of participants |
| Vehicle Control Combined | Proportion of Participants With Lines Gained/Lost of BCVA | >=15 letter loss | 0 percentage of participants |
| Vehicle Control Combined | Proportion of Participants With Lines Gained/Lost of BCVA | 5-9 letter loss | 8.1 percentage of participants |
| Vehicle Control Combined | Proportion of Participants With Lines Gained/Lost of BCVA | >=15 letter gain | 1.4 percentage of participants |
| Vehicle Control Combined | Proportion of Participants With Lines Gained/Lost of BCVA | missing | 17.6 percentage of participants |
| Vehicle Control Combined | Proportion of Participants With Lines Gained/Lost of BCVA | 10-14 letter gain | 4.1 percentage of participants |
| Vehicle Control Combined | Proportion of Participants With Lines Gained/Lost of BCVA | 5-9 letter gain | 12.2 percentage of participants |
p-value: 0.36790% CI: [0.6722, 1.8276]odds ratio
p-value: 0.85790% CI: [0.4295, 1.1981]odds ratio
Secondary
Proportion of Participants With Mild PDR at Baseline Who Regressed to NPDR
To determine the effect of OTT166 on DRSS in participants with mild PDR (DRSS 61B) treated with topical OTT166. Regression of disease was defined as decrease in DRSS to 53 or lower. The reported data include the use of imputation according to the primary estimand as described in the protocol.
Time frame: At week 24
Population: ITT population. As was pre-specified in the study protocol, all participants assigned to receive vehicle control are reported as a single Arm/Group, Vehicle Control Combined.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OTT166 Cohort 1 | Proportion of Participants With Mild PDR at Baseline Who Regressed to NPDR | 4.533 estimated improvement percentage |
| OTT166 Cohort 2 | Proportion of Participants With Mild PDR at Baseline Who Regressed to NPDR | 2.908 estimated improvement percentage |
| Vehicle Control Combined | Proportion of Participants With Mild PDR at Baseline Who Regressed to NPDR | 6.149 estimated improvement percentage |
p-value: 0.671690% CI: [-7.26, 4.172]Mantel Haenszel
p-value: 0.841490% CI: [-9.025, 2.2]Mantel Haenszel
Secondary
Proportion That Met Objective Rescue Therapy Criteria by Week 24
To determine the effect of OTT166 on the need for rescue therapy in participants with moderately severe to severe NPDR and mild PDR. The reported data include the use of imputation according to the primary estimand as described in the protocol.
Time frame: From Baseline (Day 1) up to Week 24
Population: ITT population. As was pre-specified in the study protocol, all participants assigned to receive vehicle control are reported as a single Arm/Group, Vehicle Control Combined.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OTT166 Cohort 1 | Proportion That Met Objective Rescue Therapy Criteria by Week 24 | 20 estimated rescue percentage |
| OTT166 Cohort 2 | Proportion That Met Objective Rescue Therapy Criteria by Week 24 | 26.684 estimated rescue percentage |
| Vehicle Control Combined | Proportion That Met Objective Rescue Therapy Criteria by Week 24 | 21.622 estimated rescue percentage |
p-value: 0.40490% CI: [0.5068, 1.6556]Log Rank
p-value: 0.62490% CI: [0.6399, 1.9868]Log Rank
Secondary
The Development of CI-DME
To determine if topical OTT166 prevented or delayed the occurrence of CI-DME. CI-DME is defined as the presence of fluid in the central subfield in participants who have no fluid at baseline or CST\> 325 μm. The reported data include the use of imputation according to the primary estimand as described in the protocol. The percentages of participants that developed CI-DME at Week 24 are reported.
Time frame: At week 24
Population: ITT population. As was pre-specified in the study protocol, all participants assigned to receive vehicle control are reported as a single Arm/Group, Vehicle Control Combined.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OTT166 Cohort 1 | The Development of CI-DME | 21 percentage of participants |
| OTT166 Cohort 2 | The Development of CI-DME | 32 percentage of participants |
| Vehicle Control Combined | The Development of CI-DME | 27 percentage of participants |
p-value: 0.23790% CI: [0.4675, 1.392]Log Rank
p-value: 0.76690% CI: [0.7795, 2.0981]Log Rank
Secondary
Time to Development of PDR Worse Than Mild (DRSS 65 and Above) or CI-DME
To determine if topical OTT166 prevented or delayed the occurrence of PDR worse than mild (DRSS 65 and above) or CI-DME. CI-DME is defined as the presence of fluid in the central subfield in participants who have no fluid at baseline or CST\> 325 μm. Participants who experienced one or more events (worse than mild PDR and/or CI-DME), the earliest event date was selected. Participants who did not experience either event were censored at the earliest of the last available assessment. Median time to event is reported if calculable.
Time frame: From Baseline (Day 1) up to Week 24
Population: ITT population. As was pre-specified in the study protocol, all participants assigned to receive vehicle control are reported as a single Arm/Group, Vehicle Control Combined.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| OTT166 Cohort 1 | Time to Development of PDR Worse Than Mild (DRSS 65 and Above) or CI-DME | NA median time to event (days) |
| OTT166 Cohort 2 | Time to Development of PDR Worse Than Mild (DRSS 65 and Above) or CI-DME | NA median time to event (days) |
| Vehicle Control Combined | Time to Development of PDR Worse Than Mild (DRSS 65 and Above) or CI-DME | NA median time to event (days) |
p-value: 0.26890% CI: [0.533, 1.334]Log Rank
p-value: 0.30490% CI: [0.738, 1.775]Log Rank
Other Pre-specified
Proportion of Participants That Develop a VTC by Week 24 for DRSS Levels 47 and 53 at Baseline
A pre-specified sub group analysis of the NPDR population (DRSS 47 or 53) for the development of a VTC defined as worse than mild PDR, CI-DME or ASNV. The reported data include the use of imputation according to the primary estimand as described in the protocol.
Time frame: 24 weeks
Population: ITT population. As was pre-specified in the study protocol, all participants assigned to receive vehicle control are reported as a single Arm/Group, Vehicle Control Combined.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OTT166 Cohort 1 | Proportion of Participants That Develop a VTC by Week 24 for DRSS Levels 47 and 53 at Baseline | 17.3559 estimated risk percentage |
| OTT166 Cohort 2 | Proportion of Participants That Develop a VTC by Week 24 for DRSS Levels 47 and 53 at Baseline | 26.9180 estimated risk percentage |
| Vehicle Control Combined | Proportion of Participants That Develop a VTC by Week 24 for DRSS Levels 47 and 53 at Baseline | 30.5254 estimated risk percentage |
p-value: 0.04590% CI: [-27.1319, -0.4134]Mantel Haenszel
p-value: 0.330490% CI: [-18.1549, 10.5081]Mantel Haenszel
Other Pre-specified
Proportion of Participants Who Developed CI-DME at Week 24 for Randomization Strata DRSS 47 and 53
A measure of the ability to prevent CI-DME in participants with NPDR treated with OTT166. The proportion of patients that develop CI-DME (defined as new fluid in patients with no fluid at baseline or CST \> 325 microns) by week 24. This is a pre-specified sub group analysis and excludes the participants in the DRSS 61B stratum. The reported data include the use of imputation according to the primary estimand as described in the protocol.
Time frame: 24 weeks
Population: ITT population. As was pre-specified in the study protocol, all participants assigned to receive vehicle control are reported as a single Arm/Group, Vehicle Control Combined.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OTT166 Cohort 1 | Proportion of Participants Who Developed CI-DME at Week 24 for Randomization Strata DRSS 47 and 53 | 13.6949 estimated percentage of participants |
| OTT166 Cohort 2 | Proportion of Participants Who Developed CI-DME at Week 24 for Randomization Strata DRSS 47 and 53 | 20.8033 estimated percentage of participants |
| Vehicle Control Combined | Proportion of Participants Who Developed CI-DME at Week 24 for Randomization Strata DRSS 47 and 53 | 28.0508 estimated percentage of participants |
p-value: 0.027590% CI: [-27.6462, -2.1293]Mantel Haenszel
p-value: 0.17990% CI: [-21.0688, 5.9617]Mantel Haenszel