| 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. | 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. | Posted | | Number | 90% Confidence Interval | estimated improvement percentage | | At week 24 | | | | ID | Title | Description |
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| OG000 | OTT166 Cohort 1 | Participants received OTT166 5% twice a day for 24 weeks in the study eye | | OG001 | OTT166 Cohort 2 | Participants received OTT166 four times a day for 24 weeks in the study eye | | OG002 | Vehicle Control Combined | The combination of the vehicle control twice a day and the vehicle control four times a day groups. Comparisons are made between the two OTT166 dose groups and the combined vehicle control. |
| | | Title | Denominators | Categories |
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| | | Title | Measurements |
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| - OG00012.187(5.557 to 18.816)
- OG00112.263(5.297 to 19.229)
- OG00213.311(6.260 to 20.361)
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| | Group IDs | Group Description | Statistical Method | Statistical Comment | P-Value | P-Value Comment | Parameter Type | Parameter Value | Dispersion Type | Dispersion Value | Confidence Interval Sides | Confidence Interval % | CI Lower Limit | CI Upper Limit | CI Lower Limit Comment | CI Upper Limit Comment | Estimate Comment | Tested Non-Inferiority | Non-Inferiority Type | Non-Inferiority Comment | Other Analysis Description |
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| The study was powered to provide a 90% probability to detect a 20% difference between each treatment arm and the combined vehicle control. | Mantel Haenszel | MH test is adjusted for the randomization stratification factor (Screening DRSS score 47 or 53 or 61B). | 0.5730 | | difference in percentage of participants | -1.064 | | | 2-Sided | 90 | -10.578 | 8.449 | | | A single imputation (non-response) when applying composite variable strategy. MI based for missing data at Week 24, assuming MAR when applying hypothetical strategy. Kept in the analysis when applying treatment policy strategy. | | |
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| 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. | 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. | Posted | | Number | 90% Confidence Interval | estimated risk percentage | | At week 24 | | | | ID | Title | Description |
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| OG000 | OTT166 Cohort 1 | Participants received OTT166 5% twice a day for 24 weeks in the study eye | | OG001 | OTT166 Cohort 2 | Participants received OTT166 four times a day for 24 weeks in the study eye | | OG002 | Vehicle Control Combined | The combination of the vehicle control twice a day and the vehicle control four times a day groups. Comparisons are made between the two OTT166 dose groups and the combined vehicle control. |
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| 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. | 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. | Posted | | Number | 90% Confidence Interval | estimated risk percentage | | At week 24 | | | | ID | Title | Description |
|---|
| OG000 | OTT166 Cohort 1 | Participants received OTT166 5% twice a day for 24 weeks in the study eye | | OG001 | OTT166 Cohort 2 | Participants received OTT166 four times a day for 24 weeks in the study eye | | OG002 | Vehicle Control Combined | The combination of the vehicle control twice a day and the vehicle control four times a day groups. Comparisons are made between the two OTT166 dose groups and the combined vehicle control. |
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| 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. | 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. | Posted | | Number | 90% Confidence Interval | percentage of participants | | At week 24 | | | | ID | Title | Description |
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| OG000 | OTT166 Cohort 1 | Participants received OTT166 5% twice a day for 24 weeks in the study eye | | OG001 | OTT166 Cohort 2 | Participants received OTT166 four times a day for 24 weeks in the study eye | | OG002 | Vehicle Control Combined | The combination of the vehicle control twice a day and the vehicle control four times a day groups. Comparisons are made between the two OTT166 dose groups and the combined vehicle control. |
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| 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. | 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. | Posted | | Number | 90% Confidence Interval | estimated risk percentage | | At week 24 | | | | ID | Title | Description |
|---|
| OG000 | OTT166 Cohort 1 | Participants received OTT166 5% twice a day for 24 weeks in the study eye | | OG001 | OTT166 Cohort 2 | Participants received OTT166 four times a day for 24 weeks in the study eye | | OG002 | Vehicle Control Combined | The combination of the vehicle control twice a day and the vehicle control four times a day groups. Comparisons are made between the two OTT166 dose groups and the combined vehicle control. |
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| 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. | 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. | Posted | | Number | 90% Confidence Interval | percentage of participants | | At week 24 | | | | ID | Title | Description |
|---|
| OG000 | OTT166 Cohort 1 | Participants received OTT166 5% twice a day for 24 weeks in the study eye | | OG001 | OTT166 Cohort 2 | Participants received OTT166 four times a day for 24 weeks in the study eye | | OG002 | Vehicle Control Combined | The combination of the vehicle control twice a day and the vehicle control four times a day groups. Comparisons are made between the two OTT166 dose groups and the combined vehicle control. |
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| 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. | 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. | Posted | | Number | 90% Confidence Interval | estimated risk percentage | | At Week 24 | | | | ID | Title | Description |
|---|
| OG000 | OTT166 Cohort 1 | Participants received OTT166 5% twice a day for 24 weeks in the study eye | | OG001 | OTT166 Cohort 2 | Participants received OTT166 four times a day for 24 weeks in the study eye | | OG002 | Vehicle Control Combined | The combination of the vehicle control twice a day and the vehicle control four times a day groups. Comparisons are made between the two OTT166 dose groups and the combined vehicle control. |
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| 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. | 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. | Posted | | Median | 90% Confidence Interval | median time to event (days) | | From Baseline (Day 1) up to Week 24 | | | | ID | Title | Description |
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| OG000 | OTT166 Cohort 1 | Participants received OTT166 5% twice a day for 24 weeks in the study eye | | OG001 | OTT166 Cohort 2 | Participants received OTT166 four times a day for 24 weeks in the study eye | | OG002 | Vehicle Control Combined | The combination of the vehicle control twice a day and the vehicle control four times a day groups. Comparisons are made between the two OTT166 dose groups and the combined vehicle control. |
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| 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. | 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. | Posted | | Number | | percentage of participants | | At week 24 | | | | ID | Title | Description |
|---|
| OG000 | OTT166 Cohort 1 | Participants received OTT166 5% twice a day for 24 weeks in the study eye | | OG001 | OTT166 Cohort 2 | Participants received OTT166 four times a day for 24 weeks in the study eye | | OG002 | Vehicle Control Combined | The combination of the vehicle control twice a day and the vehicle control four times a day groups. Comparisons are made between the two OTT166 dose groups and the combined vehicle control. |
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| 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. | 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. | Posted | | Number | 90% Confidence Interval | estimated improvement percentage | | At week 24 | | | | ID | Title | Description |
|---|
| OG000 | OTT166 Cohort 1 | Participants received OTT166 5% twice a day for 24 weeks in the study eye | | OG001 | OTT166 Cohort 2 | Participants received OTT166 four times a day for 24 weeks in the study eye | | OG002 | Vehicle Control Combined | The combination of the vehicle control twice a day and the vehicle control four times a day groups. Comparisons are made between the two OTT166 dose groups and the combined vehicle control. |
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| 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. | 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. | Posted | | Least Squares Mean | Standard Error | ETDRS letters | | From Baseline (Day 1) up to Week 24 | | | | ID | Title | Description |
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| OG000 | OTT166 Cohort 1 | Participants received OTT166 5% twice a day for 24 weeks in the study eye | | OG001 | OTT166 Cohort 2 | Participants received OTT166 four times a day for 24 weeks in the study eye | | OG002 | Vehicle Control Combined | The combination of the vehicle control twice a day and the vehicle control four times a day groups. Comparisons are made between the two OTT166 dose groups and the combined vehicle control. |
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| 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. | 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. | Posted | | Number | | percentage of participants | | From Baseline (Day 1) up to Week 24 | | | | ID | Title | Description |
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| OG000 | OTT166 Cohort 1 | Participants received OTT166 5% twice a day for 24 weeks in the study eye | | OG001 | OTT166 Cohort 2 | Participants received OTT166 four times a day for 24 weeks in the study eye | | OG002 | Vehicle Control Combined | The combination of the vehicle control twice a day and the vehicle control four times a day groups. Comparisons are made between the two OTT166 dose groups and the combined vehicle control. |
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| 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. | 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. | Posted | | Least Squares Mean | Standard Error | letters*day | | From Baseline (Day 1) up to Week 24 | | | | ID | Title | Description |
|---|
| OG000 | OTT166 Cohort 1 | Participants received OTT166 5% twice a day for 24 weeks in the study eye | | OG001 | OTT166 Cohort 2 | Participants received OTT166 four times a day for 24 weeks in the study eye | | OG002 | Vehicle Control Combined | The combination of the vehicle control twice a day and the vehicle control four times a day groups. Comparisons are made between the two OTT166 dose groups and the combined vehicle control. |
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| 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). | 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. | Posted | | Least Squares Mean | Standard Error | microns | | From Baseline (Day 1) up to Week 24 | | | | ID | Title | Description |
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| OG000 | OTT166 Cohort 1 | Participants received OTT166 5% twice a day for 24 weeks in the study eye | | OG001 | OTT166 Cohort 2 | Participants received OTT166 four times a day for 24 weeks in the study eye | | OG002 | Vehicle Control Combined | The combination of the vehicle control twice a day and the vehicle control four times a day groups. Comparisons are made between the two OTT166 dose groups and the combined vehicle control. |
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| 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. | 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. | Posted | | Least Squares Mean | Standard Error | microns*day | | From Baseline (Day 1) up to Week 24 | | | | ID | Title | Description |
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| OG000 | OTT166 Cohort 1 | Participants received OTT166 5% twice a day for 24 weeks in the study eye | | OG001 | OTT166 Cohort 2 | Participants received OTT166 four times a day for 24 weeks in the study eye | | OG002 | Vehicle Control Combined | The combination of the vehicle control twice a day and the vehicle control four times a day groups. Comparisons are made between the two OTT166 dose groups and the combined vehicle control. |
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| 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. | 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. | Posted | | Number | 90% Confidence Interval | estimated percentage | | From Baseline (Day 1) up to Week 24 | | | | ID | Title | Description |
|---|
| OG000 | OTT166 Cohort 1 | Participants received OTT166 5% twice a day for 24 weeks in the study eye | | OG001 | OTT166 Cohort 2 | Participants received OTT166 four times a day for 24 weeks in the study eye | | OG002 | Vehicle Control Combined | The combination of the vehicle control twice a day and the vehicle control four times a day groups. Comparisons are made between the two OTT166 dose groups and the combined vehicle control. |
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| 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. | 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. | Posted | | Number | 90% Confidence Interval | estimated rescue percentage | | From Baseline (Day 1) up to Week 24 | | | | ID | Title | Description |
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| OG000 | OTT166 Cohort 1 | Participants received OTT166 5% twice a day for 24 weeks in the study eye | | OG001 | OTT166 Cohort 2 | Participants received OTT166 four times a day for 24 weeks in the study eye | | OG002 | Vehicle Control Combined | The combination of the vehicle control twice a day and the vehicle control four times a day groups. Comparisons are made between the two OTT166 dose groups and the combined vehicle control. |
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| 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. | 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. | Posted | | Number | 90% Confidence Interval | estimated percentage of participants | | 24 Weeks | | | | ID | Title | Description |
|---|
| OG000 | OTT166 Cohort 1 | Participants received OTT166 5% twice a day for 24 weeks in the study eye | | OG001 | OTT166 Cohort 2 | Participants received OTT166 four times a day for 24 weeks in the study eye | | OG002 | Vehicle Control Combined | The combination of the vehicle control twice a day and the vehicle control four times a day groups. Comparisons are made between the two OTT166 dose groups and the combined vehicle control. |
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| 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. | 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. | Posted | | Number | 90% Confidence Interval | estimated risk percentage | | 24 weeks | | | | ID | Title | Description |
|---|
| OG000 | OTT166 Cohort 1 | Participants received OTT166 5% twice a day for 24 weeks in the study eye | | OG001 | OTT166 Cohort 2 | Participants received OTT166 four times a day for 24 weeks in the study eye | | OG002 | Vehicle Control Combined | The combination of the vehicle control twice a day and the vehicle control four times a day groups. Comparisons are made between the two OTT166 dose groups and the combined vehicle control. |
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| 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. | 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. | Posted | | Number | 90% Confidence Interval | estimated percentage of participants | | 24 weeks | | | | ID | Title | Description |
|---|
| OG000 | OTT166 Cohort 1 | Participants received OTT166 5% twice a day for 24 weeks in the study eye | | OG001 | OTT166 Cohort 2 | Participants received OTT166 four times a day for 24 weeks in the study eye | | OG002 | Vehicle Control Combined | The combination of the vehicle control twice a day and the vehicle control four times a day groups. Comparisons are made between the two OTT166 dose groups and the combined vehicle control. |
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