Trial Outcomes & Findings for Nesvategrast (OTT166) in Diabetic Retinopathy (DR) (NCT NCT05409235)
NCT ID: NCT05409235
Last Updated: 2024-08-09
Results Overview
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.
COMPLETED
PHASE2
225 participants
At week 24
2024-08-09
Participant Flow
Participant milestones
| Measure |
OTT166 Cohort 1
Participants will receive OTT166 low dose for 24 weeks
OTT166: Participants will receive OTT166 5% ophthalmic solution twice a day for 24 weeks
|
OTT166 Cohort 2
Participants will receive OTT166 high dose for 24 weeks
OTT166: Participants will receive OTT166 5% ophthalmic solution four time a day for 24 weeks
|
Vehicle Control Cohort 1
Participants will receive vehicle control for 24 weeks
Vehicle control: Participants will receive vehicle control twice a day for 24 weeks
|
Vehicle Control Cohort 2
Participants will receive vehicle control for 24 weeks
Vehicle control: Participants will receive vehicle control four times a day for 24 weeks
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
75
|
76
|
38
|
36
|
|
Overall Study
COMPLETED
|
70
|
65
|
34
|
30
|
|
Overall Study
NOT COMPLETED
|
5
|
11
|
4
|
6
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Nesvategrast (OTT166) in Diabetic Retinopathy (DR)
Baseline characteristics by cohort
| Measure |
OTT166 Cohort 1
n=75 Participants
Participants received OTT166 low dose for 24 weeks
OTT166: Participants received OTT166 5% ophthalmic solution twice a day for 24 weeks
|
OTT166 Cohort 2
n=76 Participants
Participants received OTT166 high dose for 24 weeks
OTT166: Participants received OTT166 5% ophthalmic solution four times a day for 24 weeks
|
Vehicle Control Cohort 1
n=38 Participants
Participants received vehicle control for 24 weeks
Vehicle control: Participants received vehicle control twice a day for 24 weeks
|
Vehicle Control Cohort 2
n=36 Participants
Participants received vehicle control for 24 weeks
Vehicle control: Participants received vehicle control four times a day for 24 weeks
|
Total
n=225 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
54 Participants
n=99 Participants
|
57 Participants
n=107 Participants
|
25 Participants
n=206 Participants
|
28 Participants
n=7 Participants
|
164 Participants
n=31 Participants
|
|
Age, Categorical
>=65 years
|
21 Participants
n=99 Participants
|
19 Participants
n=107 Participants
|
13 Participants
n=206 Participants
|
8 Participants
n=7 Participants
|
61 Participants
n=31 Participants
|
|
Age, Continuous
|
56.7 years
n=99 Participants
|
56.8 years
n=107 Participants
|
57.7 years
n=206 Participants
|
53.9 years
n=7 Participants
|
56.4 years
n=31 Participants
|
|
Sex: Female, Male
Female
|
38 Participants
n=99 Participants
|
32 Participants
n=107 Participants
|
13 Participants
n=206 Participants
|
12 Participants
n=7 Participants
|
95 Participants
n=31 Participants
|
|
Sex: Female, Male
Male
|
37 Participants
n=99 Participants
|
44 Participants
n=107 Participants
|
25 Participants
n=206 Participants
|
24 Participants
n=7 Participants
|
130 Participants
n=31 Participants
|
|
Race/Ethnicity, Customized
Asian
|
4 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
2 Participants
n=7 Participants
|
11 Participants
n=31 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
12 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
3 Participants
n=7 Participants
|
24 Participants
n=31 Participants
|
|
Race/Ethnicity, Customized
White
|
55 Participants
n=99 Participants
|
66 Participants
n=107 Participants
|
31 Participants
n=206 Participants
|
30 Participants
n=7 Participants
|
182 Participants
n=31 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
4 Participants
n=31 Participants
|
|
Race/Ethnicity, Customized
Not reported
|
3 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=31 Participants
|
|
Body mass index
|
34.1 kg/m^2
n=99 Participants
|
33.4 kg/m^2
n=107 Participants
|
33.2 kg/m^2
n=206 Participants
|
34.1 kg/m^2
n=7 Participants
|
34.1 kg/m^2
n=31 Participants
|
|
Hemoglobin a1c
|
8.56 % of RBCs with glycosylated hemoglobin
n=99 Participants
|
8.50 % of RBCs with glycosylated hemoglobin
n=107 Participants
|
8.37 % of RBCs with glycosylated hemoglobin
n=206 Participants
|
8.64 % of RBCs with glycosylated hemoglobin
n=7 Participants
|
8.52 % of RBCs with glycosylated hemoglobin
n=31 Participants
|
|
Diabetic retinopathy Severity Scale at Screening
DRSS 47
|
47 participants
n=99 Participants
|
46 participants
n=107 Participants
|
23 participants
n=206 Participants
|
23 participants
n=7 Participants
|
139 participants
n=31 Participants
|
|
Diabetic retinopathy Severity Scale at Screening
DRSS 53
|
13 participants
n=99 Participants
|
14 participants
n=107 Participants
|
7 participants
n=206 Participants
|
6 participants
n=7 Participants
|
40 participants
n=31 Participants
|
|
Diabetic retinopathy Severity Scale at Screening
DRSS 61B
|
15 participants
n=99 Participants
|
16 participants
n=107 Participants
|
8 participants
n=206 Participants
|
7 participants
n=7 Participants
|
46 participants
n=31 Participants
|
|
Best corrected visual acuity
|
82.8 letters
n=99 Participants
|
82.6 letters
n=107 Participants
|
82.9 letters
n=206 Participants
|
83.4 letters
n=7 Participants
|
82.9 letters
n=31 Participants
|
|
Central subfield thickness (CST)
|
252.18 microns
n=99 Participants
|
260.72 microns
n=107 Participants
|
262.01 microns
n=206 Participants
|
256.53 microns
n=7 Participants
|
257.42 microns
n=31 Participants
|
|
Duration of Diabetic Retinopathy
|
1.699 years
n=99 Participants
|
1.896 years
n=107 Participants
|
2.667 years
n=206 Participants
|
1.166 years
n=7 Participants
|
1.843 years
n=31 Participants
|
PRIMARY outcome
Timeframe: At week 24Population: 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.
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.
Outcome measures
| Measure |
OTT166 Cohort 1
n=75 Participants
Participants received OTT166 5% twice a day for 24 weeks in the study eye
|
OTT166 Cohort 2
n=76 Participants
Participants received OTT166 four times a day for 24 weeks in the study eye
|
Vehicle Control Combined
n=74 Participants
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.
|
|---|---|---|---|
|
Proportion of Participants Who Improved by ≥ 2 Steps From Baseline in Diabetic Retinopathy Severity Scale (DRSS) Scores
|
12.187 estimated improvement percentage
Interval 5.557 to 18.816
|
12.263 estimated improvement percentage
Interval 5.297 to 19.229
|
13.311 estimated improvement percentage
Interval 6.26 to 20.361
|
SECONDARY outcome
Timeframe: At week 24Population: 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.
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.
Outcome measures
| Measure |
OTT166 Cohort 1
n=75 Participants
Participants received OTT166 5% twice a day for 24 weeks in the study eye
|
OTT166 Cohort 2
n=76 Participants
Participants received OTT166 four times a day for 24 weeks in the study eye
|
Vehicle Control Combined
n=74 Participants
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.
|
|---|---|---|---|
|
Proportion of Participants That Developed Worse Than Mild PDR (DRSS 65 and Above)
|
12.467 estimated risk percentage
Interval 6.105 to 18.828
|
15.316 estimated risk percentage
Interval 8.158 to 22.473
|
9.405 estimated risk percentage
Interval 3.503 to 15.307
|
SECONDARY outcome
Timeframe: At week 24Population: 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.
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.
Outcome measures
| Measure |
OTT166 Cohort 1
n=75 Participants
Participants received OTT166 5% twice a day for 24 weeks in the study eye
|
OTT166 Cohort 2
n=76 Participants
Participants received OTT166 four times a day for 24 weeks in the study eye
|
Vehicle Control Combined
n=74 Participants
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.
|
|---|---|---|---|
|
Proportion of Participants Who Developed ASNV
|
4.200 estimated risk percentage
Interval 0.285 to 8.115
|
4.487 estimated risk percentage
Interval 0.288 to 8.686
|
6.068 estimated risk percentage
Interval 1.243 to 10.892
|
SECONDARY outcome
Timeframe: At week 24Population: 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.
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.
Outcome measures
| Measure |
OTT166 Cohort 1
n=75 Participants
Participants received OTT166 5% twice a day for 24 weeks in the study eye
|
OTT166 Cohort 2
n=76 Participants
Participants received OTT166 four times a day for 24 weeks in the study eye
|
Vehicle Control Combined
n=74 Participants
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.
|
|---|---|---|---|
|
Development of PDR Worse Than Mild (Wtm) (DRSS 65 and Above)
|
13 percentage of participants
Interval 7.46 to 20.75
|
17 percentage of participants
Interval 10.88 to 25.82
|
16 percentage of participants
Interval 10.24 to 25.35
|
SECONDARY outcome
Timeframe: At week 24Population: 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.
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.
Outcome measures
| Measure |
OTT166 Cohort 1
n=75 Participants
Participants received OTT166 5% twice a day for 24 weeks in the study eye
|
OTT166 Cohort 2
n=76 Participants
Participants received OTT166 four times a day for 24 weeks in the study eye
|
Vehicle Control Combined
n=74 Participants
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.
|
|---|---|---|---|
|
Proportion of Participants Who Developed CI-DME
|
14.827 estimated risk percentage
Interval 7.787 to 21.867
|
20.513 estimated risk percentage
Interval 12.331 to 28.695
|
25.459 estimated risk percentage
Interval 16.581 to 34.338
|
SECONDARY outcome
Timeframe: At week 24Population: 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.
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.
Outcome measures
| Measure |
OTT166 Cohort 1
n=75 Participants
Participants received OTT166 5% twice a day for 24 weeks in the study eye
|
OTT166 Cohort 2
n=76 Participants
Participants received OTT166 four times a day for 24 weeks in the study eye
|
Vehicle Control Combined
n=74 Participants
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.
|
|---|---|---|---|
|
The Development of CI-DME
|
21 percentage of participants
Interval 14.44 to 30.65
|
32 percentage of participants
Interval 23.93 to 42.11
|
27 percentage of participants
Interval 19.65 to 37.37
|
SECONDARY outcome
Timeframe: At Week 24Population: 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.
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.
Outcome measures
| Measure |
OTT166 Cohort 1
n=75 Participants
Participants received OTT166 5% twice a day for 24 weeks in the study eye
|
OTT166 Cohort 2
n=76 Participants
Participants received OTT166 four times a day for 24 weeks in the study eye
|
Vehicle Control Combined
n=74 Participants
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.
|
|---|---|---|---|
|
Proportion of Participants That Developed Visually Threatening Complications (VTC) Complications (VTC)
|
23.387 estimated risk percentage
Interval 14.99 to 31.783
|
28.829 estimated risk percentage
Interval 19.73 to 37.928
|
29.838 estimated risk percentage
Interval 20.442 to 39.233
|
SECONDARY outcome
Timeframe: From Baseline (Day 1) up to Week 24Population: 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.
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.
Outcome measures
| Measure |
OTT166 Cohort 1
n=75 Participants
Participants received OTT166 5% twice a day for 24 weeks in the study eye
|
OTT166 Cohort 2
n=76 Participants
Participants received OTT166 four times a day for 24 weeks in the study eye
|
Vehicle Control Combined
n=74 Participants
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.
|
|---|---|---|---|
|
Time to Development of PDR Worse Than Mild (DRSS 65 and Above) or CI-DME
|
NA median time to event (days)
median and 90% confidence interval were not calculable due to an insufficient number of participants having events
|
NA median time to event (days)
median and 90% confidence interval were not calculable due to an insufficient number of participants having events
|
NA median time to event (days)
median and 90% confidence interval were not calculable due to an insufficient number of participants having events
|
SECONDARY outcome
Timeframe: At week 24Population: 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.
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.
Outcome measures
| Measure |
OTT166 Cohort 1
n=75 Participants
Participants received OTT166 5% twice a day for 24 weeks in the study eye
|
OTT166 Cohort 2
n=76 Participants
Participants received OTT166 four times a day for 24 weeks in the study eye
|
Vehicle Control Combined
n=74 Participants
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.
|
|---|---|---|---|
|
Proportion of Participants With Change in DRSS Steps at Week 24 Compared to Baseline
Improved by ≥3 steps
|
4.0 percentage of participants
|
1.3 percentage of participants
|
6.8 percentage of participants
|
|
Proportion of Participants With Change in DRSS Steps at Week 24 Compared to Baseline
Improved by 2 steps
|
8.0 percentage of participants
|
7.9 percentage of participants
|
4.1 percentage of participants
|
|
Proportion of Participants With Change in DRSS Steps at Week 24 Compared to Baseline
Improved by 1 step
|
18.7 percentage of participants
|
17.1 percentage of participants
|
27.0 percentage of participants
|
|
Proportion of Participants With Change in DRSS Steps at Week 24 Compared to Baseline
No change
|
44.0 percentage of participants
|
36.8 percentage of participants
|
29.7 percentage of participants
|
|
Proportion of Participants With Change in DRSS Steps at Week 24 Compared to Baseline
Worsened by 1 step
|
6.7 percentage of participants
|
5.3 percentage of participants
|
8.1 percentage of participants
|
|
Proportion of Participants With Change in DRSS Steps at Week 24 Compared to Baseline
Worsened by 2 steps
|
6.7 percentage of participants
|
2.6 percentage of participants
|
1.4 percentage of participants
|
|
Proportion of Participants With Change in DRSS Steps at Week 24 Compared to Baseline
Worsened by ≥3 steps
|
1.3 percentage of participants
|
5.3 percentage of participants
|
2.7 percentage of participants
|
|
Proportion of Participants With Change in DRSS Steps at Week 24 Compared to Baseline
missing
|
10.7 percentage of participants
|
23.7 percentage of participants
|
20.3 percentage of participants
|
SECONDARY outcome
Timeframe: At week 24Population: 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.
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.
Outcome measures
| Measure |
OTT166 Cohort 1
n=75 Participants
Participants received OTT166 5% twice a day for 24 weeks in the study eye
|
OTT166 Cohort 2
n=76 Participants
Participants received OTT166 four times a day for 24 weeks in the study eye
|
Vehicle Control Combined
n=74 Participants
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.
|
|---|---|---|---|
|
Proportion of Participants With Mild PDR at Baseline Who Regressed to NPDR
|
4.533 estimated improvement percentage
Interval 0.437 to 8.629
|
2.908 estimated improvement percentage
Interval -0.687 to 6.502
|
6.149 estimated improvement percentage
Interval 1.329 to 10.968
|
SECONDARY outcome
Timeframe: From Baseline (Day 1) up to Week 24Population: 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.
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.
Outcome measures
| Measure |
OTT166 Cohort 1
n=75 Participants
Participants received OTT166 5% twice a day for 24 weeks in the study eye
|
OTT166 Cohort 2
n=76 Participants
Participants received OTT166 four times a day for 24 weeks in the study eye
|
Vehicle Control Combined
n=74 Participants
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.
|
|---|---|---|---|
|
Change From Baseline in Best Corrected Visual Acuity (BCVA)
|
-0.5829 ETDRS letters
Standard Error 1.0530
|
-2.3353 ETDRS letters
Standard Error 1.0647
|
-0.0504 ETDRS letters
Standard Error 1.0594
|
SECONDARY outcome
Timeframe: From Baseline (Day 1) up to Week 24Population: 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.
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.
Outcome measures
| Measure |
OTT166 Cohort 1
n=75 Participants
Participants received OTT166 5% twice a day for 24 weeks in the study eye
|
OTT166 Cohort 2
n=76 Participants
Participants received OTT166 four times a day for 24 weeks in the study eye
|
Vehicle Control Combined
n=74 Participants
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.
|
|---|---|---|---|
|
Proportion of Participants With Lines Gained/Lost of BCVA
>=15 letter gain
|
0 percentage of participants
|
0 percentage of participants
|
1.4 percentage of participants
|
|
Proportion of Participants With Lines Gained/Lost of BCVA
10-14 letter gain
|
2.7 percentage of participants
|
1.3 percentage of participants
|
4.1 percentage of participants
|
|
Proportion of Participants With Lines Gained/Lost of BCVA
5-9 letter gain
|
20.0 percentage of participants
|
9.2 percentage of participants
|
12.2 percentage of participants
|
|
Proportion of Participants With Lines Gained/Lost of BCVA
1-4 letter gain
|
30.7 percentage of participants
|
30.3 percentage of participants
|
27.0 percentage of participants
|
|
Proportion of Participants With Lines Gained/Lost of BCVA
0 letter loss or gain
|
8.0 percentage of participants
|
13.2 percentage of participants
|
5.4 percentage of participants
|
|
Proportion of Participants With Lines Gained/Lost of BCVA
1-4 letter loss
|
21.3 percentage of participants
|
13.2 percentage of participants
|
23.0 percentage of participants
|
|
Proportion of Participants With Lines Gained/Lost of BCVA
5-9 letter loss
|
4.0 percentage of participants
|
9.2 percentage of participants
|
8.1 percentage of participants
|
|
Proportion of Participants With Lines Gained/Lost of BCVA
10-14 letter loss
|
1.3 percentage of participants
|
2.6 percentage of participants
|
1.4 percentage of participants
|
|
Proportion of Participants With Lines Gained/Lost of BCVA
>=15 letter loss
|
1.3 percentage of participants
|
2.6 percentage of participants
|
0 percentage of participants
|
|
Proportion of Participants With Lines Gained/Lost of BCVA
missing
|
10.7 percentage of participants
|
18.4 percentage of participants
|
17.6 percentage of participants
|
SECONDARY outcome
Timeframe: From Baseline (Day 1) up to Week 24Population: 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.
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.
Outcome measures
| Measure |
OTT166 Cohort 1
n=75 Participants
Participants received OTT166 5% twice a day for 24 weeks in the study eye
|
OTT166 Cohort 2
n=76 Participants
Participants received OTT166 four times a day for 24 weeks in the study eye
|
Vehicle Control Combined
n=74 Participants
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.
|
|---|---|---|---|
|
Area Under the Curve for BCVA (ETDRS Letters) From Baseline to Week 24
|
1997.9673 letters*day
Standard Error 19.3899
|
1977.5682 letters*day
Standard Error 19.1258
|
1993.8143 letters*day
Standard Error 19.4706
|
SECONDARY outcome
Timeframe: From Baseline (Day 1) up to Week 24Population: 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.
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).
Outcome measures
| Measure |
OTT166 Cohort 1
n=75 Participants
Participants received OTT166 5% twice a day for 24 weeks in the study eye
|
OTT166 Cohort 2
n=76 Participants
Participants received OTT166 four times a day for 24 weeks in the study eye
|
Vehicle Control Combined
n=74 Participants
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.
|
|---|---|---|---|
|
Change From Baseline in Central Subfield Thickness (CST)
|
14.479 microns
Standard Error 4.0974
|
9.365 microns
Standard Error 4.1020
|
10.416 microns
Standard Error 4.1107
|
SECONDARY outcome
Timeframe: From Baseline (Day 1) up to Week 24Population: 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.
To determine the effect of OTT166 on CST in participants with moderately severe to severe NPDR and mild PDR. CST was measured by OCT.
Outcome measures
| Measure |
OTT166 Cohort 1
n=75 Participants
Participants received OTT166 5% twice a day for 24 weeks in the study eye
|
OTT166 Cohort 2
n=76 Participants
Participants received OTT166 four times a day for 24 weeks in the study eye
|
Vehicle Control Combined
n=74 Participants
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.
|
|---|---|---|---|
|
Area Under The Curve (AUC) for Change From Baseline in CST
|
6.308 microns*day
Standard Error 0.0568
|
6.296 microns*day
Standard Error 0.0561
|
6.287 microns*day
Standard Error 0.0567
|
SECONDARY outcome
Timeframe: From Baseline (Day 1) up to Week 24Population: 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.
To determine the effect of OTT166 on the need for rescue therapy in participants with moderately severe to severe NPDR and mild PDR.
Outcome measures
| Measure |
OTT166 Cohort 1
n=75 Participants
Participants received OTT166 5% twice a day for 24 weeks in the study eye
|
OTT166 Cohort 2
n=76 Participants
Participants received OTT166 four times a day for 24 weeks in the study eye
|
Vehicle Control Combined
n=74 Participants
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.
|
|---|---|---|---|
|
Proportion of Participants Who Met the Objective Rescue Criteria
|
20.000 estimated percentage
Interval 12.752 to 29.113
|
23.684 estimated percentage
Interval 15.902 to 33.071
|
21.622 estimated percentage
Interval 14.058 to 30.969
|
SECONDARY outcome
Timeframe: From Baseline (Day 1) up to Week 24Population: 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.
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.
Outcome measures
| Measure |
OTT166 Cohort 1
n=75 Participants
Participants received OTT166 5% twice a day for 24 weeks in the study eye
|
OTT166 Cohort 2
n=76 Participants
Participants received OTT166 four times a day for 24 weeks in the study eye
|
Vehicle Control Combined
n=74 Participants
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.
|
|---|---|---|---|
|
Proportion That Met Objective Rescue Therapy Criteria by Week 24
|
20 estimated rescue percentage
Interval 12.752 to 29.113
|
26.684 estimated rescue percentage
Interval 15.902 to 33.071
|
21.622 estimated rescue percentage
Interval 14.058 to 30.969
|
SECONDARY outcome
Timeframe: 24 WeeksPopulation: 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.
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.
Outcome measures
| Measure |
OTT166 Cohort 1
n=75 Participants
Participants received OTT166 5% twice a day for 24 weeks in the study eye
|
OTT166 Cohort 2
n=76 Participants
Participants received OTT166 four times a day for 24 weeks in the study eye
|
Vehicle Control Combined
n=74 Participants
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.
|
|---|---|---|---|
|
Percentages of Participants at Week 24 That Had Had Rescue Therapy Administered
|
4 estimated percentage of participants
Interval 1.67 to 10.67
|
6 estimated percentage of participants
Interval 2.72 to 13.33
|
4 estimated percentage of participants
Interval 1.71 to 10.87
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 24 weeksPopulation: 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.
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.
Outcome measures
| Measure |
OTT166 Cohort 1
n=60 Participants
Participants received OTT166 5% twice a day for 24 weeks in the study eye
|
OTT166 Cohort 2
n=60 Participants
Participants received OTT166 four times a day for 24 weeks in the study eye
|
Vehicle Control Combined
n=59 Participants
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.
|
|---|---|---|---|
|
Proportion of Participants That Develop a VTC by Week 24 for DRSS Levels 47 and 53 at Baseline
|
17.3559 estimated risk percentage
Interval 8.813 to 25.8988
|
26.9180 estimated risk percentage
Interval 17.0207 to 36.8154
|
30.5254 estimated risk percentage
Interval 19.9191 to 41.1318
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 24 weeksPopulation: 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.
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.
Outcome measures
| Measure |
OTT166 Cohort 1
n=60 Participants
Participants received OTT166 5% twice a day for 24 weeks in the study eye
|
OTT166 Cohort 2
n=60 Participants
Participants received OTT166 four times a day for 24 weeks in the study eye
|
Vehicle Control Combined
n=59 Participants
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.
|
|---|---|---|---|
|
Proportion of Participants Who Developed CI-DME at Week 24 for Randomization Strata DRSS 47 and 53
|
13.6949 estimated percentage of participants
Interval 5.9131 to 21.4767
|
20.8033 estimated percentage of participants
Interval 11.7263 to 29.8803
|
28.0508 estimated percentage of participants
Interval 17.7603 to 38.3414
|
Adverse Events
OTT166 Cohort 1
OTT166 Cohort 2
Vehicle Control Cohort 1
Vehicle Control Cohort 2
Serious adverse events
| Measure |
OTT166 Cohort 1
n=75 participants at risk
Participants received OTT166 5% twice a day for 24 weeks in the study eye
|
OTT166 Cohort 2
n=76 participants at risk
Participants received OTT166 four times a day for 24 weeks in the study eye
|
Vehicle Control Cohort 1
n=38 participants at risk
Participants received vehicle control twice a day for 24 weeks in the study eye
|
Vehicle Control Cohort 2
n=36 participants at risk
Participants received vehicle control four times a day for 24 weeks in the study eye
|
|---|---|---|---|---|
|
Infections and infestations
Escherichia urinary tract infection
|
0.00%
0/75 • Adverse event data were collected over 6 months
|
1.3%
1/76 • Adverse event data were collected over 6 months
|
0.00%
0/38 • Adverse event data were collected over 6 months
|
0.00%
0/36 • Adverse event data were collected over 6 months
|
|
Infections and infestations
Pneumonia
|
1.3%
1/75 • Adverse event data were collected over 6 months
|
0.00%
0/76 • Adverse event data were collected over 6 months
|
0.00%
0/38 • Adverse event data were collected over 6 months
|
0.00%
0/36 • Adverse event data were collected over 6 months
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/75 • Adverse event data were collected over 6 months
|
1.3%
1/76 • Adverse event data were collected over 6 months
|
0.00%
0/38 • Adverse event data were collected over 6 months
|
2.8%
1/36 • Adverse event data were collected over 6 months
|
|
Infections and infestations
Pyelonephritis acute
|
0.00%
0/75 • Adverse event data were collected over 6 months
|
1.3%
1/76 • Adverse event data were collected over 6 months
|
0.00%
0/38 • Adverse event data were collected over 6 months
|
0.00%
0/36 • Adverse event data were collected over 6 months
|
|
Infections and infestations
Sepsis
|
0.00%
0/75 • Adverse event data were collected over 6 months
|
1.3%
1/76 • Adverse event data were collected over 6 months
|
0.00%
0/38 • Adverse event data were collected over 6 months
|
0.00%
0/36 • Adverse event data were collected over 6 months
|
|
Infections and infestations
Appendicitis
|
0.00%
0/75 • Adverse event data were collected over 6 months
|
0.00%
0/76 • Adverse event data were collected over 6 months
|
0.00%
0/38 • Adverse event data were collected over 6 months
|
2.8%
1/36 • Adverse event data were collected over 6 months
|
|
Cardiac disorders
Cardiac failure congestive
|
0.00%
0/75 • Adverse event data were collected over 6 months
|
1.3%
1/76 • Adverse event data were collected over 6 months
|
0.00%
0/38 • Adverse event data were collected over 6 months
|
0.00%
0/36 • Adverse event data were collected over 6 months
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/75 • Adverse event data were collected over 6 months
|
1.3%
1/76 • Adverse event data were collected over 6 months
|
0.00%
0/38 • Adverse event data were collected over 6 months
|
0.00%
0/36 • Adverse event data were collected over 6 months
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/75 • Adverse event data were collected over 6 months
|
1.3%
1/76 • Adverse event data were collected over 6 months
|
0.00%
0/38 • Adverse event data were collected over 6 months
|
0.00%
0/36 • Adverse event data were collected over 6 months
|
|
Gastrointestinal disorders
Diarrhoea
|
1.3%
1/75 • Adverse event data were collected over 6 months
|
0.00%
0/76 • Adverse event data were collected over 6 months
|
0.00%
0/38 • Adverse event data were collected over 6 months
|
0.00%
0/36 • Adverse event data were collected over 6 months
|
|
Gastrointestinal disorders
Constipation
|
1.3%
1/75 • Adverse event data were collected over 6 months
|
1.3%
1/76 • Adverse event data were collected over 6 months
|
0.00%
0/38 • Adverse event data were collected over 6 months
|
0.00%
0/36 • Adverse event data were collected over 6 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic carcinoma
|
1.3%
1/75 • Adverse event data were collected over 6 months
|
0.00%
0/76 • Adverse event data were collected over 6 months
|
0.00%
0/38 • Adverse event data were collected over 6 months
|
0.00%
0/36 • Adverse event data were collected over 6 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
0.00%
0/75 • Adverse event data were collected over 6 months
|
1.3%
1/76 • Adverse event data were collected over 6 months
|
0.00%
0/38 • Adverse event data were collected over 6 months
|
0.00%
0/36 • Adverse event data were collected over 6 months
|
|
Vascular disorders
Accelerated hypertension
|
1.3%
1/75 • Adverse event data were collected over 6 months
|
0.00%
0/76 • Adverse event data were collected over 6 months
|
0.00%
0/38 • Adverse event data were collected over 6 months
|
0.00%
0/36 • Adverse event data were collected over 6 months
|
|
Vascular disorders
Hypotension
|
1.3%
1/75 • Adverse event data were collected over 6 months
|
0.00%
0/76 • Adverse event data were collected over 6 months
|
0.00%
0/38 • Adverse event data were collected over 6 months
|
0.00%
0/36 • Adverse event data were collected over 6 months
|
|
Vascular disorders
Hypertension
|
0.00%
0/75 • Adverse event data were collected over 6 months
|
0.00%
0/76 • Adverse event data were collected over 6 months
|
0.00%
0/38 • Adverse event data were collected over 6 months
|
2.8%
1/36 • Adverse event data were collected over 6 months
|
|
Vascular disorders
Hypertensive emergency
|
0.00%
0/75 • Adverse event data were collected over 6 months
|
0.00%
0/76 • Adverse event data were collected over 6 months
|
0.00%
0/38 • Adverse event data were collected over 6 months
|
2.8%
1/36 • Adverse event data were collected over 6 months
|
|
Ear and labyrinth disorders
Vertigo
|
1.3%
1/75 • Adverse event data were collected over 6 months
|
0.00%
0/76 • Adverse event data were collected over 6 months
|
0.00%
0/38 • Adverse event data were collected over 6 months
|
0.00%
0/36 • Adverse event data were collected over 6 months
|
|
Injury, poisoning and procedural complications
Foot fracture
|
0.00%
0/75 • Adverse event data were collected over 6 months
|
1.3%
1/76 • Adverse event data were collected over 6 months
|
0.00%
0/38 • Adverse event data were collected over 6 months
|
0.00%
0/36 • Adverse event data were collected over 6 months
|
|
Injury, poisoning and procedural complications
Tibia fracture
|
0.00%
0/75 • Adverse event data were collected over 6 months
|
1.3%
1/76 • Adverse event data were collected over 6 months
|
0.00%
0/38 • Adverse event data were collected over 6 months
|
0.00%
0/36 • Adverse event data were collected over 6 months
|
|
Musculoskeletal and connective tissue disorders
Spinal stenosis
|
1.3%
1/75 • Adverse event data were collected over 6 months
|
0.00%
0/76 • Adverse event data were collected over 6 months
|
0.00%
0/38 • Adverse event data were collected over 6 months
|
0.00%
0/36 • Adverse event data were collected over 6 months
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/75 • Adverse event data were collected over 6 months
|
0.00%
0/76 • Adverse event data were collected over 6 months
|
0.00%
0/38 • Adverse event data were collected over 6 months
|
2.8%
1/36 • Adverse event data were collected over 6 months
|
|
Nervous system disorders
Cranial nerve paralysis
|
1.3%
1/75 • Adverse event data were collected over 6 months
|
0.00%
0/76 • Adverse event data were collected over 6 months
|
0.00%
0/38 • Adverse event data were collected over 6 months
|
0.00%
0/36 • Adverse event data were collected over 6 months
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/75 • Adverse event data were collected over 6 months
|
0.00%
0/76 • Adverse event data were collected over 6 months
|
2.6%
1/38 • Adverse event data were collected over 6 months
|
2.8%
1/36 • Adverse event data were collected over 6 months
|
|
Psychiatric disorders
Alcohol abuse
|
1.3%
1/75 • Adverse event data were collected over 6 months
|
0.00%
0/76 • Adverse event data were collected over 6 months
|
0.00%
0/38 • Adverse event data were collected over 6 months
|
0.00%
0/36 • Adverse event data were collected over 6 months
|
|
Eye disorders
Macular hole
|
0.00%
0/75 • Adverse event data were collected over 6 months
|
0.00%
0/76 • Adverse event data were collected over 6 months
|
0.00%
0/38 • Adverse event data were collected over 6 months
|
2.8%
1/36 • Adverse event data were collected over 6 months
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/75 • Adverse event data were collected over 6 months
|
0.00%
0/76 • Adverse event data were collected over 6 months
|
2.6%
1/38 • Adverse event data were collected over 6 months
|
0.00%
0/36 • Adverse event data were collected over 6 months
|
Other adverse events
| Measure |
OTT166 Cohort 1
n=75 participants at risk
Participants received OTT166 5% twice a day for 24 weeks in the study eye
|
OTT166 Cohort 2
n=76 participants at risk
Participants received OTT166 four times a day for 24 weeks in the study eye
|
Vehicle Control Cohort 1
n=38 participants at risk
Participants received vehicle control twice a day for 24 weeks in the study eye
|
Vehicle Control Cohort 2
n=36 participants at risk
Participants received vehicle control four times a day for 24 weeks in the study eye
|
|---|---|---|---|---|
|
Eye disorders
Punctate keratitis
|
13.3%
10/75 • Adverse event data were collected over 6 months
|
15.8%
12/76 • Adverse event data were collected over 6 months
|
7.9%
3/38 • Adverse event data were collected over 6 months
|
8.3%
3/36 • Adverse event data were collected over 6 months
|
|
Eye disorders
Diabetic retinopathy
|
6.7%
5/75 • Adverse event data were collected over 6 months
|
3.9%
3/76 • Adverse event data were collected over 6 months
|
7.9%
3/38 • Adverse event data were collected over 6 months
|
8.3%
3/36 • Adverse event data were collected over 6 months
|
|
Eye disorders
Cataract
|
4.0%
3/75 • Adverse event data were collected over 6 months
|
5.3%
4/76 • Adverse event data were collected over 6 months
|
0.00%
0/38 • Adverse event data were collected over 6 months
|
2.8%
1/36 • Adverse event data were collected over 6 months
|
|
Eye disorders
Diabetic retinal oedema
|
5.3%
4/75 • Adverse event data were collected over 6 months
|
3.9%
3/76 • Adverse event data were collected over 6 months
|
5.3%
2/38 • Adverse event data were collected over 6 months
|
2.8%
1/36 • Adverse event data were collected over 6 months
|
|
Eye disorders
Retinal neovascularisation
|
5.3%
4/75 • Adverse event data were collected over 6 months
|
3.9%
3/76 • Adverse event data were collected over 6 months
|
7.9%
3/38 • Adverse event data were collected over 6 months
|
2.8%
1/36 • Adverse event data were collected over 6 months
|
|
Eye disorders
Dry eye
|
1.3%
1/75 • Adverse event data were collected over 6 months
|
5.3%
4/76 • Adverse event data were collected over 6 months
|
0.00%
0/38 • Adverse event data were collected over 6 months
|
0.00%
0/36 • Adverse event data were collected over 6 months
|
|
Eye disorders
Macular oedema
|
0.00%
0/75 • Adverse event data were collected over 6 months
|
0.00%
0/76 • Adverse event data were collected over 6 months
|
5.3%
2/38 • Adverse event data were collected over 6 months
|
0.00%
0/36 • Adverse event data were collected over 6 months
|
|
Infections and infestations
Pneumonia
|
0.00%
0/75 • Adverse event data were collected over 6 months
|
0.00%
0/76 • Adverse event data were collected over 6 months
|
0.00%
0/38 • Adverse event data were collected over 6 months
|
5.6%
2/36 • Adverse event data were collected over 6 months
|
|
Nervous system disorders
Dysgeusia
|
2.7%
2/75 • Adverse event data were collected over 6 months
|
6.6%
5/76 • Adverse event data were collected over 6 months
|
0.00%
0/38 • Adverse event data were collected over 6 months
|
0.00%
0/36 • Adverse event data were collected over 6 months
|
|
Nervous system disorders
Headache
|
1.3%
1/75 • Adverse event data were collected over 6 months
|
0.00%
0/76 • Adverse event data were collected over 6 months
|
0.00%
0/38 • Adverse event data were collected over 6 months
|
5.6%
2/36 • Adverse event data were collected over 6 months
|
|
Vascular disorders
Hypertension
|
8.0%
6/75 • Adverse event data were collected over 6 months
|
1.3%
1/76 • Adverse event data were collected over 6 months
|
0.00%
0/38 • Adverse event data were collected over 6 months
|
11.1%
4/36 • Adverse event data were collected over 6 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place