Trial Outcomes & Findings for LME636 in the Relief of Persistent Ocular Discomfort in Subjects With Severe Dry Eye Disease (NCT NCT02365519)
NCT ID: NCT02365519
Last Updated: 2018-07-02
Results Overview
Discomfort frequency and severity (each graded on a separate 100-units scale) were assessed daily using a visual analog scale (VAS) displayed on a handheld digital Pad (electronic patient-reported outcome (ePRO)). Frequency score was in response to the question 'how often your eyes felt uncomfortable during the past 24 hours' ranging from 'Rarely' to 'All the time.' Severity score was in response to the question 'how uncomfortable your eyes felt during the past 24 hours' ranging from 'Very mildly uncomfortable' to 'Very severely uncomfortable.' The Global Ocular Discomfort Score, ranging from 0 to 100, was calculated for any given day, as the square root of the product of the discomfort frequency score multiplied by the discomfort severity score. Improvement results in a reduction of the discomfort frequency or severity, or both, translating into a reduction of the resulting Global Ocular Discomfort score as compared to baseline. A negative change from baseline indicates improvement.
COMPLETED
PHASE2
514 participants
Baseline (Day 43), Day 71
2018-07-02
Participant Flow
Subjects were recruited from 31 investigational sites located in the US.
Of the 514 enrolled, 213 subjects entered the vehicle run-in period and 134 entered the randomized treatment period.
Participant milestones
| Measure |
Vehicle Run-In
All subjects exposed to LME636 Vehicle prior to the initiation of randomized study treatment
|
LME636
All subjects exposed to LME636 ophthalmic solution during randomized study treatment
|
Vehicle
All subjects exposed to LME636 Vehicle during randomized study treatment
|
|---|---|---|---|
|
Vehicle Run-In
STARTED
|
213
|
0
|
0
|
|
Vehicle Run-In
COMPLETED
|
134
|
0
|
0
|
|
Vehicle Run-In
NOT COMPLETED
|
79
|
0
|
0
|
|
Randomized and Treated
STARTED
|
0
|
69
|
65
|
|
Randomized and Treated
COMPLETED
|
0
|
67
|
64
|
|
Randomized and Treated
NOT COMPLETED
|
0
|
2
|
1
|
Reasons for withdrawal
| Measure |
Vehicle Run-In
All subjects exposed to LME636 Vehicle prior to the initiation of randomized study treatment
|
LME636
All subjects exposed to LME636 ophthalmic solution during randomized study treatment
|
Vehicle
All subjects exposed to LME636 Vehicle during randomized study treatment
|
|---|---|---|---|
|
Randomized and Treated
Adverse Event
|
0
|
1
|
0
|
|
Randomized and Treated
Withdrawal by Subject
|
0
|
1
|
1
|
Baseline Characteristics
LME636 in the Relief of Persistent Ocular Discomfort in Subjects With Severe Dry Eye Disease
Baseline characteristics by cohort
| Measure |
LME636
n=69 Participants
All subjects randomized and treated with LME636 ophthalmic solution
|
Vehicle
n=65 Participants
All subjects randomized and treated with LME636 Vehicle
|
Total
n=134 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
61.7 years
STANDARD_DEVIATION 13.05 • n=5 Participants
|
58.8 years
STANDARD_DEVIATION 14.48 • n=7 Participants
|
60.3 years
STANDARD_DEVIATION 13.78 • n=5 Participants
|
|
Sex: Female, Male
Female
|
61 Participants
n=5 Participants
|
54 Participants
n=7 Participants
|
115 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline (Day 43), Day 71Population: This analysis population includes all randomized subjects with at least a post-baseline primary endpoint assessment excluding all subjects who met the critical deviation criteria (Per-Protocol Set). Number Analyzed is the number of subjects with data at visit.
Discomfort frequency and severity (each graded on a separate 100-units scale) were assessed daily using a visual analog scale (VAS) displayed on a handheld digital Pad (electronic patient-reported outcome (ePRO)). Frequency score was in response to the question 'how often your eyes felt uncomfortable during the past 24 hours' ranging from 'Rarely' to 'All the time.' Severity score was in response to the question 'how uncomfortable your eyes felt during the past 24 hours' ranging from 'Very mildly uncomfortable' to 'Very severely uncomfortable.' The Global Ocular Discomfort Score, ranging from 0 to 100, was calculated for any given day, as the square root of the product of the discomfort frequency score multiplied by the discomfort severity score. Improvement results in a reduction of the discomfort frequency or severity, or both, translating into a reduction of the resulting Global Ocular Discomfort score as compared to baseline. A negative change from baseline indicates improvement.
Outcome measures
| Measure |
LME636
n=67 Participants
LME636 ophthalmic solution, 1 drop (approx. 40 µL; 2.4 mg) administered topically in each eye TID for 6 weeks
|
Vehicle
n=64 Participants
LME636 Vehicle, 1 drop administered topically in each eye TID for 6 weeks
|
Run-In Only
LME636 Vehicle, 1 drop administered topically in each eye TID for 4 weeks with exit prior to start of randomized treatment
|
|---|---|---|---|
|
Mean Change From Baseline in Global Ocular Discomfort Score at Day 71
|
-7.9 units on a scale
Standard Error 1.45
|
-3.6 units on a scale
Standard Error 1.49
|
—
|
PRIMARY outcome
Timeframe: Baseline (Day 43), Day 57, Day 71, Day 85Population: This analysis population includes all subjects that received any study drug (Safety Analysis Set). Number Analyzed is the number of subjects with data at visit.
Visual Acuity (VA) with the subject's best spectacles or other visual corrective devices was measured using an ETDRS visual acuity chart at 3 meters (10 feet) and reported in letters read correctly. An increase (gain) in letters read indicates improvement. Both eyes contributed to the analysis.
Outcome measures
| Measure |
LME636
n=69 Participants
LME636 ophthalmic solution, 1 drop (approx. 40 µL; 2.4 mg) administered topically in each eye TID for 6 weeks
|
Vehicle
n=65 Participants
LME636 Vehicle, 1 drop administered topically in each eye TID for 6 weeks
|
Run-In Only
LME636 Vehicle, 1 drop administered topically in each eye TID for 4 weeks with exit prior to start of randomized treatment
|
|---|---|---|---|
|
Best Corrected Visual Acuity (BCVA)
Baseline (Day 43)
|
80.6 letters
Standard Deviation 6.44
|
81.5 letters
Standard Deviation 5.72
|
—
|
|
Best Corrected Visual Acuity (BCVA)
Day 57
|
80.5 letters
Standard Deviation 6.82
|
81.6 letters
Standard Deviation 5.48
|
—
|
|
Best Corrected Visual Acuity (BCVA)
Day 71
|
81.6 letters
Standard Deviation 5.56
|
81.9 letters
Standard Deviation 5.89
|
—
|
|
Best Corrected Visual Acuity (BCVA)
Day 85
|
81.0 letters
Standard Deviation 5.73
|
81.6 letters
Standard Deviation 6.17
|
—
|
PRIMARY outcome
Timeframe: Baseline (Day 43), Day 57, Day 71, Day 85Population: Safety Analysis Set. Number Analyzed is the number of subjects with data at visit.
IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry or Tonopen and measured in millimeters of mercury (mmHg). A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). Both eyes contributed to the analysis.
Outcome measures
| Measure |
LME636
n=69 Participants
LME636 ophthalmic solution, 1 drop (approx. 40 µL; 2.4 mg) administered topically in each eye TID for 6 weeks
|
Vehicle
n=65 Participants
LME636 Vehicle, 1 drop administered topically in each eye TID for 6 weeks
|
Run-In Only
LME636 Vehicle, 1 drop administered topically in each eye TID for 4 weeks with exit prior to start of randomized treatment
|
|---|---|---|---|
|
Intraocular Pressure (IOP)
Baseline (Day 43)
|
14.8 mmHg
Standard Deviation 2.71
|
14.3 mmHg
Standard Deviation 2.63
|
—
|
|
Intraocular Pressure (IOP)
Day 57
|
14.6 mmHg
Standard Deviation 2.72
|
14.1 mmHg
Standard Deviation 2.92
|
—
|
|
Intraocular Pressure (IOP)
Day 71
|
14.0 mmHg
Standard Deviation 3.06
|
14.1 mmHg
Standard Deviation 2.70
|
—
|
|
Intraocular Pressure (IOP)
Day 85
|
14.4 mmHg
Standard Deviation 2.68
|
14.6 mmHg
Standard Deviation 2.58
|
—
|
PRIMARY outcome
Timeframe: Baseline (Day 43), Day 57, Day 71, Day 85Population: Safety Analysis Set
Ocular signs (cornea, lens, and iris/anterior chamber) were assessed by slit-lamp biomicroscopy. An increase indicates worsening. Only one eye contributed to the analysis.
Outcome measures
| Measure |
LME636
n=69 Participants
LME636 ophthalmic solution, 1 drop (approx. 40 µL; 2.4 mg) administered topically in each eye TID for 6 weeks
|
Vehicle
n=65 Participants
LME636 Vehicle, 1 drop administered topically in each eye TID for 6 weeks
|
Run-In Only
LME636 Vehicle, 1 drop administered topically in each eye TID for 4 weeks with exit prior to start of randomized treatment
|
|---|---|---|---|
|
Percentage of Subjects With Increase in Slit-Lamp Parameter From Baseline to Any Visit
Lens
|
0.0 percentage of subjects
|
0.0 percentage of subjects
|
—
|
|
Percentage of Subjects With Increase in Slit-Lamp Parameter From Baseline to Any Visit
Cornea
|
0.0 percentage of subjects
|
0.0 percentage of subjects
|
—
|
|
Percentage of Subjects With Increase in Slit-Lamp Parameter From Baseline to Any Visit
Iris
|
0.0 percentage of subjects
|
0.0 percentage of subjects
|
—
|
|
Percentage of Subjects With Increase in Slit-Lamp Parameter From Baseline to Any Visit
Anterior Chamber
|
0.0 percentage of subjects
|
0.0 percentage of subjects
|
—
|
PRIMARY outcome
Timeframe: Baseline (Day 43), Day 57, Day 71, Day 85Population: Safety Analysis Set
The dilated fundus examination was performed to evaluate the health of the vitreous, retina, macula, choroid, and optic nerve. An increase indicates worsening. Only one eye contributed to the analysis.
Outcome measures
| Measure |
LME636
n=69 Participants
LME636 ophthalmic solution, 1 drop (approx. 40 µL; 2.4 mg) administered topically in each eye TID for 6 weeks
|
Vehicle
n=65 Participants
LME636 Vehicle, 1 drop administered topically in each eye TID for 6 weeks
|
Run-In Only
LME636 Vehicle, 1 drop administered topically in each eye TID for 4 weeks with exit prior to start of randomized treatment
|
|---|---|---|---|
|
Percentage of Subjects With Increase in Dilated Fundus Parameter From Baseline to Any Visit
Vitreous
|
1.4 percentage of subjects
|
1.5 percentage of subjects
|
—
|
|
Percentage of Subjects With Increase in Dilated Fundus Parameter From Baseline to Any Visit
Retina
|
1.4 percentage of subjects
|
0.0 percentage of subjects
|
—
|
|
Percentage of Subjects With Increase in Dilated Fundus Parameter From Baseline to Any Visit
Macula
|
0.0 percentage of subjects
|
0.0 percentage of subjects
|
—
|
|
Percentage of Subjects With Increase in Dilated Fundus Parameter From Baseline to Any Visit
Choroid
|
0.0 percentage of subjects
|
0.0 percentage of subjects
|
—
|
|
Percentage of Subjects With Increase in Dilated Fundus Parameter From Baseline to Any Visit
Optic Nerve
|
0.0 percentage of subjects
|
0.0 percentage of subjects
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 43), Day 71Population: Per-Protocol Set
Discomfort frequency and severity (each graded on a separate 100-units scale) were assessed daily using a VAS displayed on a handheld ePRO. Frequency score was in response to the question 'how often your eyes felt uncomfortable during the past 24 hours' ranging from 'Rarely' to 'All the time.' Severity score was in response to the question 'how uncomfortable your eyes felt during the past 24 hours' ranging from 'Very mildly uncomfortable' to 'Very severely uncomfortable.' The Global Ocular Discomfort Score, ranging from 0 to 100, was calculated for any given day, as the square root of the product of the discomfort frequency score multiplied by the discomfort severity score. Improvement results in a reduction of the discomfort frequency or severity, or both, translating into a reduction of the resulting Global Ocular Discomfort score as compared to baseline.
Outcome measures
| Measure |
LME636
n=67 Participants
LME636 ophthalmic solution, 1 drop (approx. 40 µL; 2.4 mg) administered topically in each eye TID for 6 weeks
|
Vehicle
n=64 Participants
LME636 Vehicle, 1 drop administered topically in each eye TID for 6 weeks
|
Run-In Only
LME636 Vehicle, 1 drop administered topically in each eye TID for 4 weeks with exit prior to start of randomized treatment
|
|---|---|---|---|
|
Percentage of Subjects With More Than 20 Units Improvement in Global Ocular Discomfort Score From Baseline at Day 71
|
17.9 percentage of subjects
|
4.7 percentage of subjects
|
—
|
SECONDARY outcome
Timeframe: Day 15, Day 29, Day 43, Day 57, Day 71, Day 85Population: This analysis population includes all subjects with available pharmacokinetics data (Pharmacokinetics Analysis Set).
Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. LLOQ is defined as 0.25 ng/mL.
Outcome measures
| Measure |
LME636
n=69 Participants
LME636 ophthalmic solution, 1 drop (approx. 40 µL; 2.4 mg) administered topically in each eye TID for 6 weeks
|
Vehicle
LME636 Vehicle, 1 drop administered topically in each eye TID for 6 weeks
|
Run-In Only
LME636 Vehicle, 1 drop administered topically in each eye TID for 4 weeks with exit prior to start of randomized treatment
|
|---|---|---|---|
|
Percentage of Subjects With LME636 Serum Concentrations Below the Lower Limit of Quantification (LLOQ)
Day 15
|
100.0 percentage of subjects
|
—
|
—
|
|
Percentage of Subjects With LME636 Serum Concentrations Below the Lower Limit of Quantification (LLOQ)
Day 29
|
100.0 percentage of subjects
|
—
|
—
|
|
Percentage of Subjects With LME636 Serum Concentrations Below the Lower Limit of Quantification (LLOQ)
Day 43 (prior to administration of first dose)
|
98.5 percentage of subjects
|
—
|
—
|
|
Percentage of Subjects With LME636 Serum Concentrations Below the Lower Limit of Quantification (LLOQ)
Day 57
|
82.1 percentage of subjects
|
—
|
—
|
|
Percentage of Subjects With LME636 Serum Concentrations Below the Lower Limit of Quantification (LLOQ)
Day 71
|
71.9 percentage of subjects
|
—
|
—
|
|
Percentage of Subjects With LME636 Serum Concentrations Below the Lower Limit of Quantification (LLOQ)
Day 85 (last day of dosing)
|
67.9 percentage of subjects
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 15, Day 29, Day 43, Day 57, Day 71, Day 85Population: This analysis population includes all subjects with available immunogenicity data (Immunogenicity Analysis Set).
Samples were collected and assessed for anti-LME636 antibodies.
Outcome measures
| Measure |
LME636
n=69 Participants
LME636 ophthalmic solution, 1 drop (approx. 40 µL; 2.4 mg) administered topically in each eye TID for 6 weeks
|
Vehicle
n=65 Participants
LME636 Vehicle, 1 drop administered topically in each eye TID for 6 weeks
|
Run-In Only
n=79 Participants
LME636 Vehicle, 1 drop administered topically in each eye TID for 4 weeks with exit prior to start of randomized treatment
|
|---|---|---|---|
|
Percentage of Subjects With Anti-LME636 Antibodies by Visit
Day 71
|
79.3 percentage of subjects
|
41.7 percentage of subjects
|
—
|
|
Percentage of Subjects With Anti-LME636 Antibodies by Visit
Day 15
|
33.3 percentage of subjects
|
40.0 percentage of subjects
|
26.9 percentage of subjects
|
|
Percentage of Subjects With Anti-LME636 Antibodies by Visit
Day 29
|
37.3 percentage of subjects
|
37.7 percentage of subjects
|
27.0 percentage of subjects
|
|
Percentage of Subjects With Anti-LME636 Antibodies by Visit
Day 43 (prior to administration of first dose)
|
31.9 percentage of subjects
|
34.9 percentage of subjects
|
27.0 percentage of subjects
|
|
Percentage of Subjects With Anti-LME636 Antibodies by Visit
Day 57 (Treatment Day 15)
|
45.6 percentage of subjects
|
41.1 percentage of subjects
|
—
|
|
Percentage of Subjects With Anti-LME636 Antibodies by Visit
Day 85 (last day of dosing)
|
86.8 percentage of subjects
|
40.4 percentage of subjects
|
—
|
Adverse Events
Vehicle Run-In
LME636
Vehicle
Serious adverse events
| Measure |
Vehicle Run-In
n=213 participants at risk
All subjects exposed to LME636 Vehicle prior to the initiation of randomized study treatment
|
LME636
n=69 participants at risk
All subjects exposed to LME636 ophthalmic solution during randomized study treatment
|
Vehicle
n=65 participants at risk
All subjects exposed to LME636 Vehicle during randomized study treatment
|
|---|---|---|---|
|
Infections and infestations
Extradural abscess
|
0.47%
1/213 • Adverse events (AEs) were collected from time of informed consent for the duration of a subject's participation in the study (up to 85 days).
An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Reports of AEs were obtained through solicited and spontaneous comments from the subjects and through observations by the Investigator as outlined in the study protocol.
|
0.00%
0/69 • Adverse events (AEs) were collected from time of informed consent for the duration of a subject's participation in the study (up to 85 days).
An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Reports of AEs were obtained through solicited and spontaneous comments from the subjects and through observations by the Investigator as outlined in the study protocol.
|
0.00%
0/65 • Adverse events (AEs) were collected from time of informed consent for the duration of a subject's participation in the study (up to 85 days).
An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Reports of AEs were obtained through solicited and spontaneous comments from the subjects and through observations by the Investigator as outlined in the study protocol.
|
|
Infections and infestations
Pneumonia
|
0.00%
0/213 • Adverse events (AEs) were collected from time of informed consent for the duration of a subject's participation in the study (up to 85 days).
An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Reports of AEs were obtained through solicited and spontaneous comments from the subjects and through observations by the Investigator as outlined in the study protocol.
|
0.00%
0/69 • Adverse events (AEs) were collected from time of informed consent for the duration of a subject's participation in the study (up to 85 days).
An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Reports of AEs were obtained through solicited and spontaneous comments from the subjects and through observations by the Investigator as outlined in the study protocol.
|
1.5%
1/65 • Adverse events (AEs) were collected from time of informed consent for the duration of a subject's participation in the study (up to 85 days).
An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Reports of AEs were obtained through solicited and spontaneous comments from the subjects and through observations by the Investigator as outlined in the study protocol.
|
Other adverse events
Adverse event data not reported
Additional Information
Ophthalmology & Medical Lead, Translational Medicine, NIBR
Alcon, A Novartis Division
Results disclosure agreements
- Principal investigator is a sponsor employee Sponsor reserves the right of prior review of any publication or presentation of information related to the study.
- Publication restrictions are in place
Restriction type: OTHER