Trial Outcomes & Findings for Study to Investigate the Safety and Efficacy of K-321 in Patients With Fuchs Endothelial Corneal Dystrophy (FECD) Following Descemetorhexis (NCT NCT04250207)

NCT ID: NCT04250207

Last Updated: 2024-11-05

Results Overview

Change in Central ECD at week 12

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

65 participants

Primary outcome timeframe

Baseline to Week 12

Results posted on

2024-11-05

Participant Flow

After obtaining informed consent at Visit 1, the investigator selected one eye as the study eye, and the patient returned for the descemetorhexis operation and random assignment to treatment after 1 to 4 weeks (Visit 2). At Visit 2, eligibility for study participation was confirmed, which included the requirement of a successful descemetorhexis operation which met the inclusion criteria. After eligibility was confirmed, patients were randomly assigned to the 3 treatment groups in a 1:1:1 ratio.

Participant milestones

Participant milestones
Measure	K-321 QID K-321 ophthalmic solution 4 times daily for 12 Weeks (Morning, Mid-day, Evening, Night).	K-321 BID K-321 ophthalmic solution twice daily for 12 Weeks. (Morning: K-321, Mid-day: Placebo, Evening: Placebo, Night: K-321)	Placebo Placebo ophthalmic solution four times daily for 12 Weeks. (Morning, Mid-day, Evening, Night)
12 Week Treatment STARTED	21	22	22
12 Week Treatment COMPLETED	21	22	20
12 Week Treatment NOT COMPLETED	0	0	2
40 Week Follow-up Observation STARTED	21	22	22
40 Week Follow-up Observation COMPLETED	21	21	20
40 Week Follow-up Observation NOT COMPLETED	0	1	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study to Investigate the Safety and Efficacy of K-321 in Patients With Fuchs Endothelial Corneal Dystrophy (FECD) Following Descemetorhexis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	K-321 QID n=21 Participants K-321 ophthalmic solution 4 times daily for 12 Weeks (Morning, Mid-day, Evening, Night).	K-321 BID n=22 Participants K-321 ophthalmic solution twice daily for 12 Weeks. (Morning: K-321, Mid-day: Placebo, Evening: Placebo, Night: K-321)	Placebo n=22 Participants Placebo ophthalmic solution four times daily for 12 Weeks. (Morning, Mid-day, Evening, Night)	Total n=65 Participants Total of all reporting groups
Age, Continuous	64.7 Years STANDARD_DEVIATION 12.28 • n=5 Participants	65.1 Years STANDARD_DEVIATION 9.68 • n=7 Participants	65.3 Years STANDARD_DEVIATION 9.00 • n=5 Participants	65.03 Years STANDARD_DEVIATION 10.23 • n=4 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	13 Participants n=7 Participants	20 Participants n=5 Participants	49 Participants n=4 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	9 Participants n=7 Participants	2 Participants n=5 Participants	16 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	8 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	16 Participants n=5 Participants	21 Participants n=7 Participants	20 Participants n=5 Participants	57 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants
Race (NIH/OMB) White	20 Participants n=5 Participants	19 Participants n=7 Participants	20 Participants n=5 Participants	59 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline to Week 12

Population: Full Analysis Set (FAS)

Change in Central ECD at week 12

Outcome measures

Outcome measures
Measure	K-321 QID n=21 Participants K-321 ophthalmic solution 4 times daily for 12 Weeks (Morning, Mid-day, Evening, Night).	K-321 BID n=22 Participants K-321 ophthalmic solution twice daily for 12 Weeks. (Morning: K-321, Mid-day: Placebo, Evening: Placebo, Night: K-321)	Placebo n=22 Participants Placebo ophthalmic solution four times daily for 12 Weeks. (Morning, Mid-day, Evening, Night)
Central Corneal Endothelial Cell Density (ECD) at Week 12	530.86 cells/mm2 Standard Deviation 312.453	468.02 cells/mm2 Standard Deviation 322.361	228.05 cells/mm2 Standard Deviation 297.860

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: The number of participants analyzed for the outcome measure may differ from the overall number of participants in each group. This discrepancy can be attributed to several factors, including: * Missing data: Some participants may have incomplete data due to factors such as missed visits, early withdrawal, or loss to follow-up. * Optional visits: Week 2 was an optional visit and saw a smaller number of participants contributing data to specific outcome measures.

Outcome measures

Outcome measures
Measure	K-321 QID n=21 Participants K-321 ophthalmic solution 4 times daily for 12 Weeks (Morning, Mid-day, Evening, Night).	K-321 BID n=22 Participants K-321 ophthalmic solution twice daily for 12 Weeks. (Morning: K-321, Mid-day: Placebo, Evening: Placebo, Night: K-321)	Placebo n=22 Participants Placebo ophthalmic solution four times daily for 12 Weeks. (Morning, Mid-day, Evening, Night)
Central Corneal ECD From Baseline to Each Subsequent Visit Baseline	440.01 cells/mm2 Standard Deviation 774.300	319.06 cells/mm2 Standard Deviation 593.294	254.27 cells/mm2 Standard Deviation 468.027
Central Corneal ECD From Baseline to Each Subsequent Visit Week 1	0.00 cells/mm2 Standard Deviation 0.00	0.05 cells/mm2 Standard Deviation 0.218	0.05 cells/mm2 Standard Deviation 0.213
Central Corneal ECD From Baseline to Each Subsequent Visit Week 2	0.00 cells/mm2 Standard Deviation 0.00	0.05 cells/mm2 Standard Deviation 0.218	0.05 cells/mm2 Standard Deviation 0.213
Central Corneal ECD From Baseline to Each Subsequent Visit Week 3	131.98 cells/mm2 Standard Deviation 171.648	31.90 cells/mm2 Standard Deviation 102.749	27.49 cells/mm2 Standard Deviation 127.828
Central Corneal ECD From Baseline to Each Subsequent Visit Week 5	167.36 cells/mm2 Standard Deviation 176.049	167.94 cells/mm2 Standard Deviation 218.321	104.54 cells/mm2 Standard Deviation 218.264
Central Corneal ECD From Baseline to Each Subsequent Visit Week 7	303.14 cells/mm2 Standard Deviation 294.919	302.95 cells/mm2 Standard Deviation 232.956	79.38 cells/mm2 Standard Deviation 215.197
Central Corneal ECD From Baseline to Each Subsequent Visit Week 9	370.71 cells/mm2 Standard Deviation 338.393	340.76 cells/mm2 Standard Deviation 310.264	156.04 cells/mm2 Standard Deviation 278.455
Central Corneal ECD From Baseline to Each Subsequent Visit Week 12	530.86 cells/mm2 Standard Deviation 312.453	468.02 cells/mm2 Standard Deviation 322.361	228.05 cells/mm2 Standard Deviation 297.860
Central Corneal ECD From Baseline to Each Subsequent Visit Week 16	540.52 cells/mm2 Standard Deviation 311.004	499.77 cells/mm2 Standard Deviation 358.411	286.75 cells/mm2 Standard Deviation 350.269
Central Corneal ECD From Baseline to Each Subsequent Visit Week 20	655.20 cells/mm2 Standard Deviation 260.268	518.50 cells/mm2 Standard Deviation 296.094	347.21 cells/mm2 Standard Deviation 313.930
Central Corneal ECD From Baseline to Each Subsequent Visit Week 24	668.22 cells/mm2 Standard Deviation 313.783	541.02 cells/mm2 Standard Deviation 328.131	386.83 cells/mm2 Standard Deviation 353.840
Central Corneal ECD From Baseline to Each Subsequent Visit Week 38	722.23 cells/mm2 Standard Deviation 331.954	529.65 cells/mm2 Standard Deviation 303.691	391.10 cells/mm2 Standard Deviation 316.339
Central Corneal ECD From Baseline to Each Subsequent Visit Week 52	751.45 cells/mm2 Standard Deviation 407.259	633.05 cells/mm2 Standard Deviation 313.372	431.79 cells/mm2 Standard Deviation 327.488

SECONDARY outcome

Timeframe: Baseline to Week 52

Outcome measures

Outcome measures
Measure	K-321 QID n=21 Participants K-321 ophthalmic solution 4 times daily for 12 Weeks (Morning, Mid-day, Evening, Night).	K-321 BID n=22 Participants K-321 ophthalmic solution twice daily for 12 Weeks. (Morning: K-321, Mid-day: Placebo, Evening: Placebo, Night: K-321)	Placebo n=22 Participants Placebo ophthalmic solution four times daily for 12 Weeks. (Morning, Mid-day, Evening, Night)
Change From Baseline in Central Corneal Thickness Week 1	265.57 μm Standard Deviation 125.944	250.30 μm Standard Deviation 90.448	319.33 μm Standard Deviation 130.570
Change From Baseline in Central Corneal Thickness Week 2	237.54 μm Standard Deviation 94.157	249.14 μm Standard Deviation 90.636	315.18 μm Standard Deviation 131.996
Change From Baseline in Central Corneal Thickness Week 3	96.73 μm Standard Deviation 134.360	132.63 μm Standard Deviation 152.920	201.68 μm Standard Deviation 126.387
Change From Baseline in Central Corneal Thickness Week 5	52.71 μm Standard Deviation 109.696	32.31 μm Standard Deviation 110.784	159.95 μm Standard Deviation 128.295
Change From Baseline in Central Corneal Thickness Week 7	42.24 μm Standard Deviation 114.048	2.37 μm Standard Deviation 98.340	134.83 μm Standard Deviation 132.811
Change From Baseline in Central Corneal Thickness Week 9	10.36 μm Standard Deviation 98.235	-14.23 μm Standard Deviation 60.223	116.77 μm Standard Deviation 141.046
Change From Baseline in Central Corneal Thickness Week 12	0.59 μm Standard Deviation 86.332	-22.69 μm Standard Deviation 61.127	100.19 μm Standard Deviation 137.191
Change From Baseline in Central Corneal Thickness Week 16	2.40 μm Standard Deviation 67.680	-9.71 μm Standard Deviation 50.918	70.00 μm Standard Deviation 132.908
Change From Baseline in Central Corneal Thickness Week 20	16.99 μm Standard Deviation 90.440	-17.70 μm Standard Deviation 46.593	70.52 μm Standard Deviation 139.880
Change From Baseline in Central Corneal Thickness Week 24	10.60 μm Standard Deviation 78.376	-27.80 μm Standard Deviation 42.954	68.17 μm Standard Deviation 147.116
Change From Baseline in Central Corneal Thickness Week 38	-12.32 μm Standard Deviation 66.319	-21.40 μm Standard Deviation 42.525	63.09 μm Standard Deviation 149.562
Change From Baseline in Central Corneal Thickness Week 52	-6.74 μm Standard Deviation 65.888	-25.88 μm Standard Deviation 44.360	55.29 μm Standard Deviation 155.649

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: Proportions of patients from the FAS who achieved no corneal edema of the study eye

Outcome measures

Outcome measures
Measure	K-321 QID n=21 Participants K-321 ophthalmic solution 4 times daily for 12 Weeks (Morning, Mid-day, Evening, Night).	K-321 BID n=22 Participants K-321 ophthalmic solution twice daily for 12 Weeks. (Morning: K-321, Mid-day: Placebo, Evening: Placebo, Night: K-321)	Placebo n=22 Participants Placebo ophthalmic solution four times daily for 12 Weeks. (Morning, Mid-day, Evening, Night)
Time to Achievement of no Corneal Oedema of Study Eye	35.0 Days Interval 22.0 to 64.0	51.5 Days Interval 50.0 to 269.0	267.0 Days Interval 141.0 to 365.0

SECONDARY outcome

Timeframe: Baseline to Week 52

Outcome measures

Outcome measures
Measure	K-321 QID n=21 Participants K-321 ophthalmic solution 4 times daily for 12 Weeks (Morning, Mid-day, Evening, Night).	K-321 BID n=22 Participants K-321 ophthalmic solution twice daily for 12 Weeks. (Morning: K-321, Mid-day: Placebo, Evening: Placebo, Night: K-321)	Placebo n=22 Participants Placebo ophthalmic solution four times daily for 12 Weeks. (Morning, Mid-day, Evening, Night)
Proportion of Patients Who Achieved Central Corneal ECD of 700 Cells/mm2 or More at Each Visit Week 1	0 Participants	0 Participants	0 Participants
Proportion of Patients Who Achieved Central Corneal ECD of 700 Cells/mm2 or More at Each Visit Week 2	0 Participants	0 Participants	0 Participants
Proportion of Patients Who Achieved Central Corneal ECD of 700 Cells/mm2 or More at Each Visit Week 3	0 Participants	0 Participants	0 Participants
Proportion of Patients Who Achieved Central Corneal ECD of 700 Cells/mm2 or More at Each Visit Week 5	0 Participants	0 Participants	1 Participants
Proportion of Patients Who Achieved Central Corneal ECD of 700 Cells/mm2 or More at Each Visit Week 7	3 Participants	0 Participants	1 Participants
Proportion of Patients Who Achieved Central Corneal ECD of 700 Cells/mm2 or More at Each Visit Week 9	3 Participants	2 Participants	2 Participants
Proportion of Patients Who Achieved Central Corneal ECD of 700 Cells/mm2 or More at Each Visit Week 12	6 Participants	4 Participants	2 Participants
Proportion of Patients Who Achieved Central Corneal ECD of 700 Cells/mm2 or More at Each Visit Week 16	6 Participants	7 Participants	3 Participants
Proportion of Patients Who Achieved Central Corneal ECD of 700 Cells/mm2 or More at Each Visit Week 20	9 Participants	7 Participants	3 Participants
Proportion of Patients Who Achieved Central Corneal ECD of 700 Cells/mm2 or More at Each Visit Week 24	10 Participants	8 Participants	6 Participants
Proportion of Patients Who Achieved Central Corneal ECD of 700 Cells/mm2 or More at Each Visit Week 38	12 Participants	5 Participants	3 Participants
Proportion of Patients Who Achieved Central Corneal ECD of 700 Cells/mm2 or More at Each Visit Week 52	15 Participants	8 Participants	5 Participants

SECONDARY outcome

Timeframe: Up to 52 Weeks

Outcome measures

Outcome measures
Measure	K-321 QID n=21 Participants K-321 ophthalmic solution 4 times daily for 12 Weeks (Morning, Mid-day, Evening, Night).	K-321 BID n=22 Participants K-321 ophthalmic solution twice daily for 12 Weeks. (Morning: K-321, Mid-day: Placebo, Evening: Placebo, Night: K-321)	Placebo n=22 Participants Placebo ophthalmic solution four times daily for 12 Weeks. (Morning, Mid-day, Evening, Night)
Time to Achieve Central Corneal ECD 700 Cells/mm2 or More	141.0 Days Interval 83.0 to 363.0	181.0 Days Interval 113.0 to The curve that represents the upper confidence limits for the failure function lies under 0.50. Therefore, the upper limits of 50th (Median) event time couldn't be estimated.	273.0 Days Interval 135.0 to The curve that represents the upper confidence limits for the failure function lies under 0.50. Therefore, the upper limits of 50th (Median) event time couldn't be estimated.

SECONDARY outcome

Timeframe: Baseline up to 52 Weeks

Outcome measures

Outcome measures
Measure	K-321 QID n=21 Participants K-321 ophthalmic solution 4 times daily for 12 Weeks (Morning, Mid-day, Evening, Night).	K-321 BID n=22 Participants K-321 ophthalmic solution twice daily for 12 Weeks. (Morning: K-321, Mid-day: Placebo, Evening: Placebo, Night: K-321)	Placebo n=22 Participants Placebo ophthalmic solution four times daily for 12 Weeks. (Morning, Mid-day, Evening, Night)
Number of Patients Who Achieved Corneal Thickness Less Than or Equal to Baseline Corneal Thickness Week 9	11 Participants	16 Participants	5 Participants
Number of Patients Who Achieved Corneal Thickness Less Than or Equal to Baseline Corneal Thickness Week 12	13 Participants	17 Participants	5 Participants
Number of Patients Who Achieved Corneal Thickness Less Than or Equal to Baseline Corneal Thickness Week 1	0 Participants	0 Participants	0 Participants
Number of Patients Who Achieved Corneal Thickness Less Than or Equal to Baseline Corneal Thickness Week 2	0 Participants	0 Participants	0 Participants
Number of Patients Who Achieved Corneal Thickness Less Than or Equal to Baseline Corneal Thickness Week 3	5 Participants	3 Participants	1 Participants
Number of Patients Who Achieved Corneal Thickness Less Than or Equal to Baseline Corneal Thickness Week 5	8 Participants	9 Participants	2 Participants
Number of Patients Who Achieved Corneal Thickness Less Than or Equal to Baseline Corneal Thickness Week 7	11 Participants	13 Participants	3 Participants
Number of Patients Who Achieved Corneal Thickness Less Than or Equal to Baseline Corneal Thickness Week 16	14 Participants	13 Participants	6 Participants
Number of Patients Who Achieved Corneal Thickness Less Than or Equal to Baseline Corneal Thickness Week 20	12 Participants	14 Participants	8 Participants
Number of Patients Who Achieved Corneal Thickness Less Than or Equal to Baseline Corneal Thickness Week 24	13 Participants	17 Participants	9 Participants
Number of Patients Who Achieved Corneal Thickness Less Than or Equal to Baseline Corneal Thickness Week 38	15 Participants	16 Participants	10 Participants
Number of Patients Who Achieved Corneal Thickness Less Than or Equal to Baseline Corneal Thickness Week 52	14 Participants	15 Participants	13 Participants

SECONDARY outcome

Timeframe: Baseline to Week 52

Outcome measures

Outcome measures
Measure	K-321 QID n=21 Participants K-321 ophthalmic solution 4 times daily for 12 Weeks (Morning, Mid-day, Evening, Night).	K-321 BID n=22 Participants K-321 ophthalmic solution twice daily for 12 Weeks. (Morning: K-321, Mid-day: Placebo, Evening: Placebo, Night: K-321)	Placebo n=22 Participants Placebo ophthalmic solution four times daily for 12 Weeks. (Morning, Mid-day, Evening, Night)
Proportion of Patients Who Achieve No Corneal Oedema of Study Eye by Visit Week 1	0 Participants	0 Participants	0 Participants
Proportion of Patients Who Achieve No Corneal Oedema of Study Eye by Visit Week 2	0 Participants	0 Participants	0 Participants
Proportion of Patients Who Achieve No Corneal Oedema of Study Eye by Visit Week 3	8 Participants	0 Participants	1 Participants
Proportion of Patients Who Achieve No Corneal Oedema of Study Eye by Visit Week 5	11 Participants	4 Participants	1 Participants
Proportion of Patients Who Achieve No Corneal Oedema of Study Eye by Visit Week 7	11 Participants	12 Participants	2 Participants
Proportion of Patients Who Achieve No Corneal Oedema of Study Eye by Visit Week 9	14 Participants	12 Participants	2 Participants
Proportion of Patients Who Achieve No Corneal Oedema of Study Eye by Visit Week 12	17 Participants	12 Participants	2 Participants
Proportion of Patients Who Achieve No Corneal Oedema of Study Eye by Visit Week 16	16 Participants	13 Participants	2 Participants
Proportion of Patients Who Achieve No Corneal Oedema of Study Eye by Visit Week 20	15 Participants	12 Participants	7 Participants
Proportion of Patients Who Achieve No Corneal Oedema of Study Eye by Visit Week 24	17 Participants	13 Participants	8 Participants
Proportion of Patients Who Achieve No Corneal Oedema of Study Eye by Visit Week 38	17 Participants	13 Participants	10 Participants
Proportion of Patients Who Achieve No Corneal Oedema of Study Eye by Visit Week 52	17 Participants	13 Participants	13 Participants

SECONDARY outcome

Timeframe: Baseline up to Week 52

Outcome measures

Outcome measures
Measure	K-321 QID n=21 Participants K-321 ophthalmic solution 4 times daily for 12 Weeks (Morning, Mid-day, Evening, Night).	K-321 BID n=22 Participants K-321 ophthalmic solution twice daily for 12 Weeks. (Morning: K-321, Mid-day: Placebo, Evening: Placebo, Night: K-321)	Placebo n=22 Participants Placebo ophthalmic solution four times daily for 12 Weeks. (Morning, Mid-day, Evening, Night)
Time to Return of Corneal Thickness to Less Than or Equal to Baseline Cornea Thickness	50 Days Interval 35.0 to 110.0	50.0 Days Interval 34.0 to 66.0	165.0 Days Interval 112.0 to 366.0

SECONDARY outcome

Timeframe: Baseline to Week 52

Outcome measures

Outcome measures
Measure	K-321 QID n=21 Participants K-321 ophthalmic solution 4 times daily for 12 Weeks (Morning, Mid-day, Evening, Night).	K-321 BID n=22 Participants K-321 ophthalmic solution twice daily for 12 Weeks. (Morning: K-321, Mid-day: Placebo, Evening: Placebo, Night: K-321)	Placebo n=22 Participants Placebo ophthalmic solution four times daily for 12 Weeks. (Morning, Mid-day, Evening, Night)
Percent Change of Central Corneal Thickness From Baseline to Each Subsequent Visit Week 24	2.27 Percent Standard Deviation 14.662	-5.42 Percent Standard Deviation 5.927	2.79 Percent Standard Deviation 16.807
Percent Change of Central Corneal Thickness From Baseline to Each Subsequent Visit Week 1	45.76 Percent Standard Deviation 23.191	41.48 Percent Standard Deviation 15.582	51.41 Percent Standard Deviation 21.687
Percent Change of Central Corneal Thickness From Baseline to Each Subsequent Visit Week 2	39.03 Percent Standard Deviation 10.916	36.77 Percent Standard Deviation NA Number of Participant Analyzed is one in each Arm. Therefore SD can't be estimated.	40.97 Percent Standard Deviation NA Number of Participant Analyzed is one in each Arm. Therefore SD can't be estimated.
Percent Change of Central Corneal Thickness From Baseline to Each Subsequent Visit Week 3	16.50 Percent Standard Deviation 22.581	21.85 Percent Standard Deviation 25.600	32.39 Percent Standard Deviation 20.422
Percent Change of Central Corneal Thickness From Baseline to Each Subsequent Visit Week 5	9.24 Percent Standard Deviation 19.101	5.31 Percent Standard Deviation 17.421	25.67 Percent Standard Deviation 21.873
Percent Change of Central Corneal Thickness From Baseline to Each Subsequent Visit Week 7	7.58 Percent Standard Deviation 19.744	0.43 Percent Standard Deviation 15.276	20.84 Percent Standard Deviation 22.228
Percent Change of Central Corneal Thickness From Baseline to Each Subsequent Visit Week 9	2.51 Percent Standard Deviation 18.451	-2.28 Percent Standard Deviation 9.442	14.55 Percent Standard Deviation 18.954
Percent Change of Central Corneal Thickness From Baseline to Each Subsequent Visit Week 12	0.73 Percent Standard Deviation 15.895	-3.65 Percent Standard Deviation 9.467	10.70 Percent Standard Deviation 17.611
Percent Change of Central Corneal Thickness From Baseline to Each Subsequent Visit Week 16	0.74 Percent Standard Deviation 11.936	-1.65 Percent Standard Deviation 7.955	2.91 Percent Standard Deviation 11.967
Percent Change of Central Corneal Thickness From Baseline to Each Subsequent Visit Week 20	3.85 Percent Standard Deviation 17.227	-3.64 Percent Standard Deviation 6.726	1.93 Percent Standard Deviation 14.291
Percent Change of Central Corneal Thickness From Baseline to Each Subsequent Visit Week 38	-3.63 Percent Standard Deviation 7.992	-4.98 Percent Standard Deviation 5.229	-2.00 Percent Standard Deviation 9.969
Percent Change of Central Corneal Thickness From Baseline to Each Subsequent Visit Week 52	-2.90 Percent Standard Deviation 8.634	-5.63 Percent Standard Deviation 5.614	-3.68 Percent Standard Deviation 11.182

Adverse Events

K-321 QID

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

K-321 BID

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	K-321 QID n=21 participants at risk K-321 ophthalmic solution 4 times daily for 12 Weeks (Morning, Mid-day, Evening, Night).	K-321 BID n=22 participants at risk K-321 ophthalmic solution twice daily for 12 Weeks. (Morning: K-321, Mid-day: Placebo, Evening: Placebo, Night: K-321)	Placebo n=22 participants at risk Placebo ophthalmic solution four times daily for 12 Weeks. (Morning, Mid-day, Evening, Night)
Infections and infestations Appendicitis	0.00% 0/21 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	4.5% 1/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	0.00% 0/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.
Infections and infestations Pneumonia bacterial	0.00% 0/21 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	0.00% 0/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	4.5% 1/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.
Gastrointestinal disorders Terminal ileitis	0.00% 0/21 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	0.00% 0/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	4.5% 1/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/21 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	0.00% 0/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	4.5% 1/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.
Surgical and medical procedures Alcohol rehabilitation	0.00% 0/21 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	0.00% 0/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	4.5% 1/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.
Vascular disorders Deep vein thrombosis	0.00% 0/21 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	0.00% 0/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	4.5% 1/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.

Other adverse events

Additional Information

Director, Clinical Operations

Kowa Research Institute, Inc.

Phone: 919-433-1600

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Sponsor must review proposed publication 60 days before submission. Sponsor can request revisions and delay publication for up to 60 days to file patents. Sponsor may also require removal of specific information (other than study results).
Publication restrictions are in place

Restriction type: OTHER

Measure	K-321 QID n=21 participants at risk K-321 ophthalmic solution 4 times daily for 12 Weeks (Morning, Mid-day, Evening, Night).	K-321 BID n=22 participants at risk K-321 ophthalmic solution twice daily for 12 Weeks. (Morning: K-321, Mid-day: Placebo, Evening: Placebo, Night: K-321)	Placebo n=22 participants at risk Placebo ophthalmic solution four times daily for 12 Weeks. (Morning, Mid-day, Evening, Night)
Eye disorders Conjunctival hyperaemia	14.3% 3/21 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	13.6% 3/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	0.00% 0/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.
Eye disorders Corneal oedema	19.0% 4/21 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	9.1% 2/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	31.8% 7/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.
Eye disorders Eye pruritus	4.8% 1/21 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	13.6% 3/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	0.00% 0/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.
Eye disorders Vision blurred	4.8% 1/21 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	9.1% 2/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	13.6% 3/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.
Eye disorders Photophobia	4.8% 1/21 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	9.1% 2/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	9.1% 2/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.
Eye disorders Corneal disorder	0.00% 0/21 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	9.1% 2/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	4.5% 1/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.
Eye disorders Eye irritation	0.00% 0/21 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	9.1% 2/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	4.5% 1/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.
Eye disorders Foreign body sensation in eyes	0.00% 0/21 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	9.1% 2/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	4.5% 1/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.
Eye disorders Diplopia	0.00% 0/21 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	9.1% 2/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	0.00% 0/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.
Eye disorders Eye pain	0.00% 0/21 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	9.1% 2/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	22.7% 5/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.
Eye disorders Visual acuity reduced	4.8% 1/21 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	13.6% 3/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	0.00% 0/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.
Investigations Intraocular pressure increased	0.00% 0/21 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	4.5% 1/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	9.1% 2/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.
Infections and infestations Nasopharyngitis	4.8% 1/21 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	9.1% 2/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	0.00% 0/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.
Injury, poisoning and procedural complications Wrist fracture	0.00% 0/21 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	0.00% 0/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	9.1% 2/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.
Eye disorders Eye allergy (study eye)	9.5% 2/21 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	0.00% 0/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	0.00% 0/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.
Eye disorders Corneal degeneration	9.5% 2/21 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	4.5% 1/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	4.5% 1/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.
Eye disorders Eye allergy (non-study eye)	9.5% 2/21 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	0.00% 0/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	0.00% 0/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.
Eye disorders Punctate keratitis	4.8% 1/21 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	9.1% 2/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.	4.5% 1/22 • 52 Weeks Treatment emergent adverse events (TEAE) were any adverse event that occurred or worsened after the first dose of study treatment.