Trial Outcomes & Findings for A Study to Evaluate AXR-159 Ophthalmic Solution in Patients With Dry Eye Disease (NCT NCT03598699)
NCT ID: NCT03598699
Last Updated: 2023-10-13
Results Overview
Change from Baseline in Ora Calibra® Corneal and Conjunctival Staining Scale with a range from 0 to 4 (0=None, 1=Trace, 2=Mild, 3=Moderate, 4=Severe) in the study eye. Higher negative scores mean a better outcome.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
102 participants
Primary outcome timeframe
Month 3
Results posted on
2023-10-13
Participant Flow
Participants were recruited based on prespecified inclusion and exclusion criteria between June 2018 and September 2018. Of 265 subjects initially screened, 102 subjects were randomized. The first subject's screening visit was on June 26; the last subject's exit visit was on December 28.
All subjects who met the enrollment criteria at the initial screening visit were assigned to a 2-week run-in period on thrice daily topical vehicle. At the conclusion of the run-in period, 102 subjects again met the enrollment criteria and were randomized to either active or vehicle groups.
Participant milestones
| Measure |
AXR-159 Ophthalmic Solution 50 mg/mL
AXR-159 High Dose
AXR-159: AXR-159 Ophthalmic Solution
|
AXR-159 Ophthalmic Solution Vehicle
Control Group
AXR-159: AXR-159 Ophthalmic Solution Vehicle
|
|---|---|---|
|
Overall Study
STARTED
|
54
|
48
|
|
Overall Study
COMPLETED
|
45
|
46
|
|
Overall Study
NOT COMPLETED
|
9
|
2
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Baseline Measure population = Modified Intent-to-Treat population with LOCF; Overall population = Safety population
Baseline characteristics by cohort
| Measure |
AXR-159 Ophthalmic Solution 50 mg/mL
n=54 Participants
AXR-159 High Dose
AXR-159: AXR-159 Ophthalmic Solution
|
AXR-159 Ophthalmic Solution Vehicle
n=48 Participants
Control Group
AXR-159: AXR-159 Ophthalmic Solution Vehicle
|
Total
n=102 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
62.5 years
STANDARD_DEVIATION 10.72 • n=54 Participants
|
65.3 years
STANDARD_DEVIATION 10.18 • n=48 Participants
|
63.8 years
STANDARD_DEVIATION 10.51 • n=102 Participants
|
|
Sex: Female, Male
Female
|
42 Participants
n=54 Participants
|
33 Participants
n=48 Participants
|
75 Participants
n=102 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=54 Participants
|
15 Participants
n=48 Participants
|
27 Participants
n=102 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=54 Participants
|
1 Participants
n=48 Participants
|
4 Participants
n=102 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
51 Participants
n=54 Participants
|
47 Participants
n=48 Participants
|
98 Participants
n=102 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=54 Participants
|
0 Participants
n=48 Participants
|
0 Participants
n=102 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=54 Participants
|
0 Participants
n=48 Participants
|
0 Participants
n=102 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=54 Participants
|
1 Participants
n=48 Participants
|
1 Participants
n=102 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=54 Participants
|
0 Participants
n=48 Participants
|
0 Participants
n=102 Participants
|
|
Race (NIH/OMB)
Black or African American
|
6 Participants
n=54 Participants
|
8 Participants
n=48 Participants
|
14 Participants
n=102 Participants
|
|
Race (NIH/OMB)
White
|
47 Participants
n=54 Participants
|
39 Participants
n=48 Participants
|
86 Participants
n=102 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=54 Participants
|
0 Participants
n=48 Participants
|
1 Participants
n=102 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=54 Participants
|
0 Participants
n=48 Participants
|
0 Participants
n=102 Participants
|
|
Region of Enrollment
United States
|
54 participants
n=54 Participants
|
48 participants
n=48 Participants
|
102 participants
n=102 Participants
|
|
Inferior Corneal Staining Score
|
2.16 units on a scale
n=50 Participants • Baseline Measure population = Modified Intent-to-Treat population with LOCF; Overall population = Safety population
|
2.29 units on a scale
n=47 Participants • Baseline Measure population = Modified Intent-to-Treat population with LOCF; Overall population = Safety population
|
2.22 units on a scale
n=97 Participants • Baseline Measure population = Modified Intent-to-Treat population with LOCF; Overall population = Safety population
|
|
Eye Dryness
|
76.8 units on a scale
n=50 Participants • Baseline Measure population = Modified Intent-to-Treat population with LOCF; Overall population = Safety population
|
76.9 units on a scale
n=47 Participants • Baseline Measure population = Modified Intent-to-Treat population with LOCF; Overall population = Safety population
|
76.9 units on a scale
n=97 Participants • Baseline Measure population = Modified Intent-to-Treat population with LOCF; Overall population = Safety population
|
|
Total Ocular Surface and Disease Index (OSDI) © for Dry Eye
|
50.9 units on a scale
n=50 Participants • Baseline Measure population = Modified Intent-to-Treat population with observed data only; Overall population = Safety population
|
44.1 units on a scale
n=47 Participants • Baseline Measure population = Modified Intent-to-Treat population with observed data only; Overall population = Safety population
|
47.6 units on a scale
n=97 Participants • Baseline Measure population = Modified Intent-to-Treat population with observed data only; Overall population = Safety population
|
|
Schirmer's Test
|
5.7 millimeters
n=50 Participants • Baseline Measure population = Modified Intent-to-Treat population with observed data only; Overall population = Safety population
|
6.4 millimeters
n=47 Participants • Baseline Measure population = Modified Intent-to-Treat population with observed data only; Overall population = Safety population
|
6.0 millimeters
n=97 Participants • Baseline Measure population = Modified Intent-to-Treat population with observed data only; Overall population = Safety population
|
|
Tear Film Break-up Time (TBUT)
|
2.239 seconds
n=50 Participants • Baseline Measure population = Modified Intent-to-Treat population with observed data only; Overall population = Safety population
|
2.388 seconds
n=47 Participants • Baseline Measure population = Modified Intent-to-Treat population with observed data only; Overall population = Safety population
|
2.311 seconds
n=97 Participants • Baseline Measure population = Modified Intent-to-Treat population with observed data only; Overall population = Safety population
|
|
Conjunctival Redness Score
|
1.72 units on a scale
n=50 Participants • Baseline Measure population = Modified Intent-to-Treat population with observed data only; Overall population = Safety population
|
1.61 units on a scale
n=47 Participants • Baseline Measure population = Modified Intent-to-Treat population with observed data only; Overall population = Safety population
|
1.67 units on a scale
n=97 Participants • Baseline Measure population = Modified Intent-to-Treat population with observed data only; Overall population = Safety population
|
|
Total Lissamine Green Conjunctival Staining
|
3.28 units on a scale
n=50 Participants • Baseline Measure population = Modified Intent-to-Treat population with observed data only; Overall population = Safety population
|
2.96 units on a scale
n=47 Participants • Baseline Measure population = Modified Intent-to-Treat population with observed data only; Overall population = Safety population
|
3.12 units on a scale
n=97 Participants • Baseline Measure population = Modified Intent-to-Treat population with observed data only; Overall population = Safety population
|
PRIMARY outcome
Timeframe: Month 3Population: Modified Intent-to-Treat population with last observation carried forward (LOCF)
Change from Baseline in Ora Calibra® Corneal and Conjunctival Staining Scale with a range from 0 to 4 (0=None, 1=Trace, 2=Mild, 3=Moderate, 4=Severe) in the study eye. Higher negative scores mean a better outcome.
Outcome measures
| Measure |
AXR-159 Ophthalmic Solution 50 mg/mL
n=50 Participants
AXR-159 High Dose
AXR-159: AXR-159 Ophthalmic Solution
|
AXR-159 Ophthalmic Solution Vehicle
n=47 Participants
Control Group
AXR-159: AXR-159 Ophthalmic Solution Vehicle
|
|---|---|---|
|
Inferior Corneal Staining Score
|
-0.08 units on a scale
Standard Deviation 0.65
|
-0.03 units on a scale
Standard Deviation 0.447
|
PRIMARY outcome
Timeframe: Month 3Population: Modified Intent-to-Treat population with last observation carried forward
Change from baseline in Eye Dryness score on a subject level across both eyes. Using the visual analogue scale (VAS) subjects rated eye dryness by placing a vertical mark on the horizontal line to indicate the level of discomfort with a range of 0 to 100. 0% corresponds to "no dryness" (no discomfort) and 100% corresponds to "maximal dryness" indicating maximal discomfort. A greater negative change from baseline score means a better outcome.
Outcome measures
| Measure |
AXR-159 Ophthalmic Solution 50 mg/mL
n=50 Participants
AXR-159 High Dose
AXR-159: AXR-159 Ophthalmic Solution
|
AXR-159 Ophthalmic Solution Vehicle
n=47 Participants
Control Group
AXR-159: AXR-159 Ophthalmic Solution Vehicle
|
|---|---|---|
|
Eye Dryness
|
-12.5 units on a scale
Standard Deviation 22.62
|
-14.9 units on a scale
Standard Deviation 21.79
|
SECONDARY outcome
Timeframe: Month 3Population: Modified Intent-to-Treat with observed data only
Change from baseline in OSDI © score on a subject level. The 12-question OSDI © is assessed on a total scale from 0 to 100, where higher scores represent greater disability. A greater negative change from baseline indicates a better outcome.
Outcome measures
| Measure |
AXR-159 Ophthalmic Solution 50 mg/mL
n=45 Participants
AXR-159 High Dose
AXR-159: AXR-159 Ophthalmic Solution
|
AXR-159 Ophthalmic Solution Vehicle
n=46 Participants
Control Group
AXR-159: AXR-159 Ophthalmic Solution Vehicle
|
|---|---|---|
|
Total Ocular Surface and Disease Index (OSDI) © for Dry Eye
|
-8.8 units on a scale
Standard Deviation 9.3
|
-5.0 units on a scale
Standard Deviation 16.93
|
SECONDARY outcome
Timeframe: Month 3Population: Modified Intent-to-Treat population with observed data only
Change from baseline in Schirmer's Test score in the study eye. Unanesthetized Schirmer's Test measures the length of the moistened area of a test strip, placed in the lower temporal lid margin of each eye, in mm following a 5-minute exposure period. Greater positive numbers indicate a better outcome.
Outcome measures
| Measure |
AXR-159 Ophthalmic Solution 50 mg/mL
n=45 Participants
AXR-159 High Dose
AXR-159: AXR-159 Ophthalmic Solution
|
AXR-159 Ophthalmic Solution Vehicle
n=46 Participants
Control Group
AXR-159: AXR-159 Ophthalmic Solution Vehicle
|
|---|---|---|
|
Schirmer's Test
|
0.8 millimeters
Standard Deviation 5.13
|
1.9 millimeters
Standard Deviation 6.77
|
SECONDARY outcome
Timeframe: Month 3Population: Modified Intent-to-Treat with observed data only
Change from baseline in the study eye with a greater positive increase indicating a better outcome. Following the instillation of a sodium fluorescein solution into the inferior conjunctival cul-de-sac of each eye and several blinks over 30 seconds, the examiner monitored the integrity of the tear film with the aid of a slit lamp, noting the time it takes to form micelles from the time that the eye is opened. TBUT was measured in seconds using a stopwatch and a digital image recording system for the right eye followed by the left eye. Values reported are for the study eye.
Outcome measures
| Measure |
AXR-159 Ophthalmic Solution 50 mg/mL
n=45 Participants
AXR-159 High Dose
AXR-159: AXR-159 Ophthalmic Solution
|
AXR-159 Ophthalmic Solution Vehicle
n=46 Participants
Control Group
AXR-159: AXR-159 Ophthalmic Solution Vehicle
|
|---|---|---|
|
Tear Film Break-up Time (TBUT)
|
-0.143 seconds
Standard Deviation 1.093
|
-0.178 seconds
Standard Deviation 1.105
|
SECONDARY outcome
Timeframe: Month 3Population: Modified Intent-to-Treat population with observed data only
Change from baseline of Ora Calibra® Conjunctival Redness Scale for Dry Eye. Scores range from 0 to 4 with 0=None, 1=Trace, 2=Mild, 3=Moderate, 4=Severe; with higher numbers indicating more conjunctival redness. Greater negative numbers indicate a better outcome. Values reported are for the study eye.
Outcome measures
| Measure |
AXR-159 Ophthalmic Solution 50 mg/mL
n=45 Participants
AXR-159 High Dose
AXR-159: AXR-159 Ophthalmic Solution
|
AXR-159 Ophthalmic Solution Vehicle
n=45 Participants
Control Group
AXR-159: AXR-159 Ophthalmic Solution Vehicle
|
|---|---|---|
|
Conjunctival Redness Score
|
0.04 units on a scale
Standard Deviation 0.673
|
0.26 units on a scale
Standard Deviation 0.518
|
SECONDARY outcome
Timeframe: Month 3Population: Modified Intent-to-Treat population with observed data only
Change from baseline of Oxford Grading Scale measuring staining within a range from 0-5 (0=None, 1=Trace, 2=Mild, 3=Moderate, 4=Severe, 5=Confluent) for each panel (temporal and nasal) and 0-10 as the sum of both panel scores for the total exposed inter-palpebral conjunctiva. Larger negative numbers indicate reduced staining and a better outcome. Values reported are for the study eye.
Outcome measures
| Measure |
AXR-159 Ophthalmic Solution 50 mg/mL
n=45 Participants
AXR-159 High Dose
AXR-159: AXR-159 Ophthalmic Solution
|
AXR-159 Ophthalmic Solution Vehicle
n=46 Participants
Control Group
AXR-159: AXR-159 Ophthalmic Solution Vehicle
|
|---|---|---|
|
Total Lissamine Green Conjunctival Staining
|
0.40 units on a scale
Standard Deviation 1.912
|
0.59 units on a scale
Standard Deviation 1.758
|
Adverse Events
AXR-159 Ophthalmic Solution 50 mg/mL
Serious events: 0 serious events
Other events: 34 other events
Deaths: 0 deaths
AXR-159 Ophthalmic Solution Vehicle
Serious events: 1 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
AXR-159 Ophthalmic Solution 50 mg/mL
n=54 participants at risk
AXR-159 High Dose
AXR-159: AXR-159 Ophthalmic Solution
|
AXR-159 Ophthalmic Solution Vehicle
n=48 participants at risk
Control Group
AXR-159: AXR-159 Ophthalmic Solution Vehicle
|
|---|---|---|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
0.00%
0/54 • For each subject, AEs were reported over a 12-week study period, starting from the randomization visit and start of treatment until the exit visit. Any serious adverse event (SAE) occurring during the study period and for 12 weeks after the last dose of study drug were to be immediately reported.
All AEs spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination or other diagnostic procedures. Documentation as to the nature, date of onset, end date, severity, and relationship to Investigational Product, action(s) taken, seriousness, and outcome of any sign or symptom observed by the physician or reported by the subject upon indirect questioning.
|
2.1%
1/48 • Number of events 1 • For each subject, AEs were reported over a 12-week study period, starting from the randomization visit and start of treatment until the exit visit. Any serious adverse event (SAE) occurring during the study period and for 12 weeks after the last dose of study drug were to be immediately reported.
All AEs spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination or other diagnostic procedures. Documentation as to the nature, date of onset, end date, severity, and relationship to Investigational Product, action(s) taken, seriousness, and outcome of any sign or symptom observed by the physician or reported by the subject upon indirect questioning.
|
Other adverse events
| Measure |
AXR-159 Ophthalmic Solution 50 mg/mL
n=54 participants at risk
AXR-159 High Dose
AXR-159: AXR-159 Ophthalmic Solution
|
AXR-159 Ophthalmic Solution Vehicle
n=48 participants at risk
Control Group
AXR-159: AXR-159 Ophthalmic Solution Vehicle
|
|---|---|---|
|
Nervous system disorders
Dysgeusia
|
37.0%
20/54 • For each subject, AEs were reported over a 12-week study period, starting from the randomization visit and start of treatment until the exit visit. Any serious adverse event (SAE) occurring during the study period and for 12 weeks after the last dose of study drug were to be immediately reported.
All AEs spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination or other diagnostic procedures. Documentation as to the nature, date of onset, end date, severity, and relationship to Investigational Product, action(s) taken, seriousness, and outcome of any sign or symptom observed by the physician or reported by the subject upon indirect questioning.
|
0.00%
0/48 • For each subject, AEs were reported over a 12-week study period, starting from the randomization visit and start of treatment until the exit visit. Any serious adverse event (SAE) occurring during the study period and for 12 weeks after the last dose of study drug were to be immediately reported.
All AEs spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination or other diagnostic procedures. Documentation as to the nature, date of onset, end date, severity, and relationship to Investigational Product, action(s) taken, seriousness, and outcome of any sign or symptom observed by the physician or reported by the subject upon indirect questioning.
|
|
Infections and infestations
Nasopharyngitis
|
7.4%
4/54 • For each subject, AEs were reported over a 12-week study period, starting from the randomization visit and start of treatment until the exit visit. Any serious adverse event (SAE) occurring during the study period and for 12 weeks after the last dose of study drug were to be immediately reported.
All AEs spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination or other diagnostic procedures. Documentation as to the nature, date of onset, end date, severity, and relationship to Investigational Product, action(s) taken, seriousness, and outcome of any sign or symptom observed by the physician or reported by the subject upon indirect questioning.
|
2.1%
1/48 • For each subject, AEs were reported over a 12-week study period, starting from the randomization visit and start of treatment until the exit visit. Any serious adverse event (SAE) occurring during the study period and for 12 weeks after the last dose of study drug were to be immediately reported.
All AEs spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination or other diagnostic procedures. Documentation as to the nature, date of onset, end date, severity, and relationship to Investigational Product, action(s) taken, seriousness, and outcome of any sign or symptom observed by the physician or reported by the subject upon indirect questioning.
|
|
General disorders
Instillation site pain
|
16.7%
9/54 • For each subject, AEs were reported over a 12-week study period, starting from the randomization visit and start of treatment until the exit visit. Any serious adverse event (SAE) occurring during the study period and for 12 weeks after the last dose of study drug were to be immediately reported.
All AEs spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination or other diagnostic procedures. Documentation as to the nature, date of onset, end date, severity, and relationship to Investigational Product, action(s) taken, seriousness, and outcome of any sign or symptom observed by the physician or reported by the subject upon indirect questioning.
|
4.2%
2/48 • For each subject, AEs were reported over a 12-week study period, starting from the randomization visit and start of treatment until the exit visit. Any serious adverse event (SAE) occurring during the study period and for 12 weeks after the last dose of study drug were to be immediately reported.
All AEs spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination or other diagnostic procedures. Documentation as to the nature, date of onset, end date, severity, and relationship to Investigational Product, action(s) taken, seriousness, and outcome of any sign or symptom observed by the physician or reported by the subject upon indirect questioning.
|
|
General disorders
Instillation site pruritus
|
9.3%
5/54 • For each subject, AEs were reported over a 12-week study period, starting from the randomization visit and start of treatment until the exit visit. Any serious adverse event (SAE) occurring during the study period and for 12 weeks after the last dose of study drug were to be immediately reported.
All AEs spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination or other diagnostic procedures. Documentation as to the nature, date of onset, end date, severity, and relationship to Investigational Product, action(s) taken, seriousness, and outcome of any sign or symptom observed by the physician or reported by the subject upon indirect questioning.
|
2.1%
1/48 • For each subject, AEs were reported over a 12-week study period, starting from the randomization visit and start of treatment until the exit visit. Any serious adverse event (SAE) occurring during the study period and for 12 weeks after the last dose of study drug were to be immediately reported.
All AEs spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination or other diagnostic procedures. Documentation as to the nature, date of onset, end date, severity, and relationship to Investigational Product, action(s) taken, seriousness, and outcome of any sign or symptom observed by the physician or reported by the subject upon indirect questioning.
|
|
Eye disorders
Eyelid oedema
|
5.6%
3/54 • For each subject, AEs were reported over a 12-week study period, starting from the randomization visit and start of treatment until the exit visit. Any serious adverse event (SAE) occurring during the study period and for 12 weeks after the last dose of study drug were to be immediately reported.
All AEs spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination or other diagnostic procedures. Documentation as to the nature, date of onset, end date, severity, and relationship to Investigational Product, action(s) taken, seriousness, and outcome of any sign or symptom observed by the physician or reported by the subject upon indirect questioning.
|
4.2%
2/48 • For each subject, AEs were reported over a 12-week study period, starting from the randomization visit and start of treatment until the exit visit. Any serious adverse event (SAE) occurring during the study period and for 12 weeks after the last dose of study drug were to be immediately reported.
All AEs spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination or other diagnostic procedures. Documentation as to the nature, date of onset, end date, severity, and relationship to Investigational Product, action(s) taken, seriousness, and outcome of any sign or symptom observed by the physician or reported by the subject upon indirect questioning.
|
|
Eye disorders
Eye pruritus
|
5.6%
3/54 • For each subject, AEs were reported over a 12-week study period, starting from the randomization visit and start of treatment until the exit visit. Any serious adverse event (SAE) occurring during the study period and for 12 weeks after the last dose of study drug were to be immediately reported.
All AEs spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination or other diagnostic procedures. Documentation as to the nature, date of onset, end date, severity, and relationship to Investigational Product, action(s) taken, seriousness, and outcome of any sign or symptom observed by the physician or reported by the subject upon indirect questioning.
|
2.1%
1/48 • For each subject, AEs were reported over a 12-week study period, starting from the randomization visit and start of treatment until the exit visit. Any serious adverse event (SAE) occurring during the study period and for 12 weeks after the last dose of study drug were to be immediately reported.
All AEs spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination or other diagnostic procedures. Documentation as to the nature, date of onset, end date, severity, and relationship to Investigational Product, action(s) taken, seriousness, and outcome of any sign or symptom observed by the physician or reported by the subject upon indirect questioning.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 1. Master Clinical Development Agreement (MCDA) between AxeroVision and ORA stipulating written confidentiality agreement with third parties containing substantially similar restrictions on disclosure, use and other obligations contained in this MCDA. 2. Publication section in the Clinical Trial Protocol prohibiting individual publications without the company's consent.
- Publication restrictions are in place
Restriction type: OTHER