Trial Outcomes & Findings for CyclASol for the Treatment of Moderate to Severe Dry-eye Disease (DED) (NCT NCT02617667)

Results Overview

The primary analysis and objective of the study was to compare the two CyclASol groups versus vehicle (all blinded treatment arms) for one sign and one symptom endpoint. The open label active comparator arm was not included in the primary analysis to reduce the number of comparisons. The sign endpoint was the change from baseline in total corneal fluorescein staining at day 113. The cornea is divided into five regions: central, superior, inferior, nasal and temporal. Each region is graded from 0-3 based on the National Eye Institute scale, where 0 indicates no staining and 3 maximal staining. The total score is the sum of all these regions. The maximum score for each eye is 15.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

207 participants

Primary outcome timeframe

Baseline to 113 Days

Results posted on

2019-11-06

Participant Flow

Participant milestones

Participant milestones
Measure	CyclASol 0.05% Ophthalmic Solution Blinded treatment arm. Cyclosporine A solution (0.05%) in vehicle. Topical ocular eye drops. 1 drop in each eye, twice daily	CyclASol 0.1% Ophthalmic Solution Blinded treatment arm. Cyclosporine A solution (0.1%) in vehicle. Topical ocular eye drops. 1 drop in each eye, twice daily.	Placebo Ophthalmic Solution Blinded treatment arm. Vehicle only. Topical ocular eye drops. 1 drop in each eye, twice daily.	Restasis Active comparator, open label arm. Cyclosporine A 0.05% ophthalmic emulsion topical ocular eye drops. 1 drop in each eye, twice daily.
Overall Study STARTED	51	51	52	53
Overall Study COMPLETED	50	50	48	52
Overall Study NOT COMPLETED	1	1	4	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

CyclASol for the Treatment of Moderate to Severe Dry-eye Disease (DED)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	CyclASol 0.05% Ophthalmic Solution n=51 Participants Blinded treatment arm. Cyclosporine A solution (0.05%) in vehicle. Topical ocular eye drops. 1 drop in each eye, twice daily.	CyclASol 0.1% Ophthalmic Solution n=51 Participants Blinded treatment arm. Cyclosporine A solution (0.1%) in vehicle. Topical ocular eye drops. 1 drop in each eye, twice daily.	Placebo Ophthalmic Solution n=52 Participants Blinded treatment arm. Vehicle only. Topical ocular eye drops. 1 drop in each eye, twice daily.	Restasis n=53 Participants Active comparator, open label arm . Cyclosporine A 0.05% ophthalmic emulsion topical ocular eye drops. 1 drop in each eye, twice daily.	Total n=207 Participants Total of all reporting groups
Age, Continuous	64.3 years STANDARD_DEVIATION 10.72 • n=5 Participants	61.1 years STANDARD_DEVIATION 12.29 • n=7 Participants	61.3 years STANDARD_DEVIATION 10.45 • n=5 Participants	62.8 years STANDARD_DEVIATION 11.20 • n=4 Participants	62.4 years STANDARD_DEVIATION 11.36 • n=21 Participants
Sex: Female, Male Female	38 Participants n=5 Participants	36 Participants n=7 Participants	39 Participants n=5 Participants	40 Participants n=4 Participants	153 Participants n=21 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	15 Participants n=7 Participants	13 Participants n=5 Participants	13 Participants n=4 Participants	54 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline to 113 Days

Population: Full analysis set population for worst eye. Worst eye: Eyes were eligible for analysis if they met all inclusion criteria. If both eyes qualified, the worst eye was taken as the eye with higher (worse) staining at Visit 1. If staining was the same, the right eye was selected as the worst eye.

The primary analysis and objective of the study was to compare the two CyclASol groups versus vehicle (all blinded treatment arms) for one sign and one symptom endpoint. The open label active comparator arm was not included in the primary analysis to reduce the number of comparisons. The sign endpoint was the change from baseline in total corneal fluorescein staining at day 113. The cornea is divided into five regions: central, superior, inferior, nasal and temporal. Each region is graded from 0-3 based on the National Eye Institute scale, where 0 indicates no staining and 3 maximal staining. The total score is the sum of all these regions. The maximum score for each eye is 15.

Outcome measures

Outcome measures
Measure	CyclASol 0.05% Ophthalmic Solution n=51 Participants Blinded treatment arm. Cyclosporine A solution (0.05%) in vehicle. Topical ocular eye drops. 1 drop in each eye, twice daily.	CyclASol 0.1% Ophthalmic Solution n=51 Participants Blinded treatment arm. Cyclosporine A solution (0.1%) in vehicle. Topical ocular eye drops. 1 drop in each eye, twice daily.	Placebo Ophthalmic Solution n=52 Participants Blinded treatment arm. Vehicle only. Topical ocular eye drops. 1 drop in each eye, twice daily.
Change From Baseline (Visit 1) in Total Corneal Fluorescein Staining at 113 Days	-2.38 units on a scale Standard Deviation 2.156	-2.10 units on a scale Standard Deviation 2.252	-1.69 units on a scale Standard Deviation 2.619

PRIMARY outcome

Timeframe: Baseline to 113 Days

Population: Full analysis set population for worst eye. Worst eye: Eyes were eligible for analysis if they met all inclusion criteria. If both eyes qualified, the worst eye was taken as the eye with higher (worse) staining at Visit 1. If staining was the same, the right eye was taken.

The primary analysis and objective of the study was to compare the the two CyclASol groups versus vehicle (all blinded treatment arms) for one sign and one symptom endpoint. The open label active comparator arm was not included in the primary analysis to reduce the number of comparisons. Furthermore, the open label character could have had an impact on patient reported outcomes. The symptom endpoint was the change from baseline in severity of dryness VAS at Day 113. Dryness severity was rated from 0 to 100%, where 0% corresponds to "no dryness" and 100% corresponds to "maximum dryness".

Outcome measures

Outcome measures
Measure	CyclASol 0.05% Ophthalmic Solution n=51 Participants Blinded treatment arm. Cyclosporine A solution (0.05%) in vehicle. Topical ocular eye drops. 1 drop in each eye, twice daily.	CyclASol 0.1% Ophthalmic Solution n=51 Participants Blinded treatment arm. Cyclosporine A solution (0.1%) in vehicle. Topical ocular eye drops. 1 drop in each eye, twice daily.	Placebo Ophthalmic Solution n=52 Participants Blinded treatment arm. Vehicle only. Topical ocular eye drops. 1 drop in each eye, twice daily.
Change From Baseline (Visit 1) in Dryness Severity Visual Analog Scale (VAS) at 113 Days	-11.00 units on a scale Standard Deviation 19.362	-9.30 units on a scale Standard Deviation 27.832	-13.85 units on a scale Standard Deviation 25.301

Adverse Events

CyclASol 0.05% Ophthalmic Solution

Serious events: 2 serious events

Other events: 5 other events

Deaths: 0 deaths

CyclASol 0.1% Ophthalmic Solution

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Placebo Ophthalmic Solution

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Restasis

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	CyclASol 0.05% Ophthalmic Solution n=51 participants at risk Blinded treatment arm. Cyclosporine A solution (0.05%) in vehicle. Topical ocular eye drops. 1 drop in each eye, twice daily.	CyclASol 0.1% Ophthalmic Solution n=51 participants at risk Blinded treatment arm. Cyclosporine A solution (0.1%) in vehicle. Topical ocular eye drops. 1 drop in each eye, twice daily.	Placebo Ophthalmic Solution n=52 participants at risk Blinded treatment arm. Vehicle only Topical ocular eye drops. 1 drop in each eye, twice daily.	Restasis n=53 participants at risk Active comparator, open label arm . Cyclosporine A 0.05% ophthalmic emulsion topical ocular eye drops. 1 drop in each eye, twice daily.
Cardiac disorders Acute coronary syndrome	2.0% 1/51 • Number of events 1 • Adverse events reported were documented from the first dose of randomized study drug until the end of the last study day visit (day 113)	0.00% 0/51 • Adverse events reported were documented from the first dose of randomized study drug until the end of the last study day visit (day 113)	0.00% 0/52 • Adverse events reported were documented from the first dose of randomized study drug until the end of the last study day visit (day 113)	0.00% 0/53 • Adverse events reported were documented from the first dose of randomized study drug until the end of the last study day visit (day 113)
Cardiac disorders Myocardial infarction	2.0% 1/51 • Number of events 1 • Adverse events reported were documented from the first dose of randomized study drug until the end of the last study day visit (day 113)	0.00% 0/51 • Adverse events reported were documented from the first dose of randomized study drug until the end of the last study day visit (day 113)	0.00% 0/52 • Adverse events reported were documented from the first dose of randomized study drug until the end of the last study day visit (day 113)	0.00% 0/53 • Adverse events reported were documented from the first dose of randomized study drug until the end of the last study day visit (day 113)
Reproductive system and breast disorders Ovarian Cyst	0.00% 0/51 • Adverse events reported were documented from the first dose of randomized study drug until the end of the last study day visit (day 113)	0.00% 0/51 • Adverse events reported were documented from the first dose of randomized study drug until the end of the last study day visit (day 113)	0.00% 0/52 • Adverse events reported were documented from the first dose of randomized study drug until the end of the last study day visit (day 113)	1.9% 1/53 • Number of events 1 • Adverse events reported were documented from the first dose of randomized study drug until the end of the last study day visit (day 113)

Other adverse events

Other adverse events
Measure	CyclASol 0.05% Ophthalmic Solution n=51 participants at risk Blinded treatment arm. Cyclosporine A solution (0.05%) in vehicle. Topical ocular eye drops. 1 drop in each eye, twice daily.	CyclASol 0.1% Ophthalmic Solution n=51 participants at risk Blinded treatment arm. Cyclosporine A solution (0.1%) in vehicle. Topical ocular eye drops. 1 drop in each eye, twice daily.	Placebo Ophthalmic Solution n=52 participants at risk Blinded treatment arm. Vehicle only Topical ocular eye drops. 1 drop in each eye, twice daily.	Restasis n=53 participants at risk Active comparator, open label arm . Cyclosporine A 0.05% ophthalmic emulsion topical ocular eye drops. 1 drop in each eye, twice daily.
Eye disorders Visual acuity reduced	3.9% 2/51 • Number of events 2 • Adverse events reported were documented from the first dose of randomized study drug until the end of the last study day visit (day 113)	7.8% 4/51 • Number of events 6 • Adverse events reported were documented from the first dose of randomized study drug until the end of the last study day visit (day 113)	1.9% 1/52 • Number of events 2 • Adverse events reported were documented from the first dose of randomized study drug until the end of the last study day visit (day 113)	7.5% 4/53 • Number of events 6 • Adverse events reported were documented from the first dose of randomized study drug until the end of the last study day visit (day 113)
Infections and infestations Nasopharyngitis	5.9% 3/51 • Number of events 3 • Adverse events reported were documented from the first dose of randomized study drug until the end of the last study day visit (day 113)	0.00% 0/51 • Adverse events reported were documented from the first dose of randomized study drug until the end of the last study day visit (day 113)	5.8% 3/52 • Number of events 3 • Adverse events reported were documented from the first dose of randomized study drug until the end of the last study day visit (day 113)	0.00% 0/53 • Adverse events reported were documented from the first dose of randomized study drug until the end of the last study day visit (day 113)

Additional Information

Dr Sonja Krösser, VP Preclinical and Clinical Development

Novaliq GmbH

Phone: +49 6221 50259-0

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60