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| Name | Class |
|---|---|
| Novartis Institutes for BioMedical Research | OTHER |
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The purpose of this study is to evaluate the efficacy of LME636 compared to vehicle in the reduction of ocular symptoms and to evaluate the safety and tolerability of LME636, when administered topically for up to 42 days, in subjects with severe dry eye disease.
This study is organized into 2 phases. Following a 2-week identification phase, eligible subjects with severe dry eye disease (DED) will be randomized into the treatment phase and will be dispensed study treatment for 10 weeks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LME636 | Experimental | LME636 ophthalmic solution, 1 drop (approx. 40 µL; 2.4 mg) administered topically in each eye 3 times a day (TID) for 6 weeks |
|
| Vehicle | Placebo Comparator | LME636 Vehicle, 1 drop administered topically in each eye TID for 6 weeks |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LME636 ophthalmic solution | Biological |
| ||
| LME636 Vehicle |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Change From Baseline in Global Ocular Discomfort Score at Day 71 | 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. | Baseline (Day 43), Day 71 |
| Best Corrected Visual Acuity (BCVA) | 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. | Baseline (Day 43), Day 57, Day 71, Day 85 |
| Intraocular Pressure (IOP) | 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. | Baseline (Day 43), Day 57, Day 71, Day 85 |
| Percentage of Subjects With Increase in Slit-Lamp Parameter From Baseline to Any Visit | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Subjects With More Than 20 Units Improvement in Global Ocular Discomfort Score From Baseline at Day 71 | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Senior Clinical Manager, GCRA | Alcon, A Novartis Division | Study Director |
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Of the 514 enrolled, 213 subjects entered the vehicle run-in period and 134 entered the randomized treatment period.
Subjects were recruited from 31 investigational sites located in the US.
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| ID | Title | Description |
|---|---|---|
| FG000 | Vehicle Run-In | All subjects exposed to LME636 Vehicle prior to the initiation of randomized study treatment |
| FG001 | LME636 | All subjects exposed to LME636 ophthalmic solution during randomized study treatment |
| FG002 | Vehicle | All subjects exposed to LME636 Vehicle during randomized study treatment |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Vehicle Run-In |
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| Randomized and Treated |
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This analysis population includes all randomized and treated subjects.
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| ID | Title | Description |
|---|---|---|
| BG000 | LME636 | All subjects randomized and treated with LME636 ophthalmic solution |
| BG001 | Vehicle | All subjects randomized and treated with LME636 Vehicle |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Mean Change From Baseline in Global Ocular Discomfort Score at Day 71 | 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. | 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. | Posted | Mean | Standard Error | units on a scale | Baseline (Day 43), Day 71 |
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Vehicle Run-In | All subjects exposed to LME636 Vehicle prior to the initiation of randomized study treatment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Extradural abscess | Infections and infestations | MedDRA (17.0) | Systematic Assessment | The subject who presented extradural abscess discontinued the study due to this AE, which was not related to the investigational product. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Ophthalmology & Medical Lead, Translational Medicine, NIBR | Alcon, A Novartis Division | 1-888-451-3937 | alcon.medinfo@alcon.com |
| ID | Term |
|---|---|
| D015352 | Dry Eye Syndromes |
| ID | Term |
|---|---|
| D007766 | Lacrimal Apparatus Diseases |
| D005128 | Eye Diseases |
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Inactive ingredients used as a placebo comparator |
|
| Baseline (Day 43), Day 57, Day 71, Day 85 |
| Percentage of Subjects With Increase in Dilated Fundus Parameter From Baseline to Any Visit | 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. | Baseline (Day 43), Day 57, Day 71, Day 85 |
| Baseline (Day 43), Day 71 |
| Percentage of Subjects With LME636 Serum Concentrations Below the Lower Limit of Quantification (LLOQ) | Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. LLOQ is defined as 0.25 ng/mL. | Day 15, Day 29, Day 43, Day 57, Day 71, Day 85 |
| Percentage of Subjects With Anti-LME636 Antibodies by Visit | Samples were collected and assessed for anti-LME636 antibodies. | Day 15, Day 29, Day 43, Day 57, Day 71, Day 85 |
| NOT COMPLETED |
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| BG002 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Primary | Best Corrected Visual Acuity (BCVA) | 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. | 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. | Posted | Mean | Standard Deviation | letters | Baseline (Day 43), Day 57, Day 71, Day 85 |
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| Primary | Intraocular Pressure (IOP) | 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. | Safety Analysis Set. Number Analyzed is the number of subjects with data at visit. | Posted | Mean | Standard Deviation | mmHg | Baseline (Day 43), Day 57, Day 71, Day 85 |
|
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| Primary | Percentage of Subjects With Increase in Slit-Lamp Parameter From Baseline to Any Visit | 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. | Safety Analysis Set | Posted | Number | percentage of subjects | Baseline (Day 43), Day 57, Day 71, Day 85 |
|
|
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| Primary | Percentage of Subjects With Increase in Dilated Fundus Parameter From Baseline to Any Visit | 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. | Safety Analysis Set | Posted | Number | percentage of subjects | Baseline (Day 43), Day 57, Day 71, Day 85 |
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| Secondary | Percentage of Subjects With More Than 20 Units Improvement in Global Ocular Discomfort Score From Baseline at Day 71 | 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. | Per-Protocol Set | Posted | Number | percentage of subjects | Baseline (Day 43), Day 71 |
|
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| Secondary | Percentage of Subjects With LME636 Serum Concentrations Below the Lower Limit of Quantification (LLOQ) | Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. LLOQ is defined as 0.25 ng/mL. | This analysis population includes all subjects with available pharmacokinetics data (Pharmacokinetics Analysis Set). | Posted | Number | percentage of subjects | Day 15, Day 29, Day 43, Day 57, Day 71, Day 85 |
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| Secondary | Percentage of Subjects With Anti-LME636 Antibodies by Visit | Samples were collected and assessed for anti-LME636 antibodies. | This analysis population includes all subjects with available immunogenicity data (Immunogenicity Analysis Set). | Posted | Number | percentage of subjects | Day 15, Day 29, Day 43, Day 57, Day 71, Day 85 |
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| 0 |
| 213 |
| 1 |
| 213 |
| 0 |
| 213 |
| EG001 | LME636 | All subjects exposed to LME636 ophthalmic solution during randomized study treatment | 0 | 69 | 0 | 69 | 0 | 69 |
| EG002 | Vehicle | All subjects exposed to LME636 Vehicle during randomized study treatment | 0 | 65 | 1 | 65 | 0 | 65 |
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| Pneumonia | Infections and infestations | MedDRA (17.0) | Systematic Assessment | Not related to investigational product |
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Sponsor reserves the right of prior review of any publication or presentation of information related to the study.
| Day 57 |
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| Iris |
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| Optic Nerve |
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