Dry Eye Disease
Conditions
Brief summary
Clinical Trial Evaluating the Safety and Tolerability of ALY688 in Subjects with Dry Eye Disease
Detailed description
This is a multi-center, randomized, double-masked Phase 1/2a trial designed to evaluate the safety and tolerability of ALY688 Ophthalmic Solution in subjects with moderate to mildly severe dry eye for 8 weeks with 6 scheduled clinic visits.
Interventions
DRUGALY688 0.1%
ALY688 0.1% Ophthalmic Solution
DRUGALY688 0.4%
ALY688 0.4% Ophthalmic Solution
DRUGVehicle
Vehicle Ophthalmic Solution
Sponsors
Allysta Pharmaceutical
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Dry eye disease for \> 3 months meeting specific sign and symptom criteria * Best correct visual acuity of +0.6 logMAR or better * Willing to sign informed consent and attend study visits * Willing to comply with contraception requirements
Exclusion criteria
* Unable to meet specific sign and symptom criteria * Signs of ophthalmic allergic, inflammatory or infectious conditions * Use of contact lenses * Anatomic abnormalities preventing accurate study assessments * Use of medications that influence eye dryness * Recent ophthalmic surgery * Unwilling to suspend current treatments for dry eye disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Adverse Events | 8 weeks | Subjects reporting any treatment-emergent adverse events |
| Eye Dryness Score (7-Day Average) | 8 weeks | Mean change from baseline in eye dryness score (7-day average) using a 0- to 100-unit visual analog scale, with 0 being better and 100 being worse |
| Corneal Fluorescein Staining | 8 weeks | Mean change from baseline in zonal corneal fluorescein staining score in study eye using a 0- to 4-unit clinical grading scale, with 0 being better and 4 being worse |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Conjunctival Hyperemia Grading | 8 weeks | Mean change from baseline in zonal conjunctival hyperemia in study eye using a 0- to 4-unit clinical grading scale and standardized grading photos, with 0 being better and 4 being worse |
| Ocular Discomfort Score by Visual Analog Scale | 8 weeks | Mean change from baseline in ocular discomfort score of 7-day average using a 0- to 100-unit visual analog scale, with 0 being better and 100 being worse |
| Schirmer's Test | 8 weeks | Mean change from baseline in tear volume in study eye as assessed by unanesthetized Schirmer test |
| Tear Film Break-up Time (TBUT) | 8 weeks | Mean change from baseline in TBUT in study eye |
| Symptom Assessment in Dry Eye (SAnDE) Score Assessment | 8 weeks | Mean change from baseline in Symptom Assessment in Dry Eye global symptom score on a 0- to 100-unit visual analog scale, with 0 being better and 100 being worse. Global symptom score is calculated as the square root of the frequency score time the severity score per visit |
| Conjunctival Lissamine Green Staining | 8 weeks | Mean change from baseline in zonal conjunctival lissamine green staining in study eye using a 0- to 4-unit clinical grading scale, with 0 being better and 4 being worse |
Countries
United States
Participant flow
Recruitment details
8 investigational sites in the United States
Participants by arm
| Arm | Count |
|---|---|
| Vehicle Ophthalmic Solution Vehicle Ophthalmic Solution (control) | 46 |
| ALY688 Ophthalmic Solution 0.1% ALY688 Ophthalmic Solution Concentration 1 | 46 |
| ALY688 Ophthalmic Solution 0.4% ALY688 Ophthalmic Solution Concentration 2 | 46 |
| Total | 138 |
Baseline characteristics
| Characteristic | Vehicle Ophthalmic Solution | ALY688 Ophthalmic Solution 0.1% | ALY688 Ophthalmic Solution 0.4% | Total |
|---|---|---|---|---|
| Age, Continuous | 62.0 years | 63.0 years | 64.5 years | 63.0 years |
| Eye Dryness Score | 66.39 units on a scale STANDARD_DEVIATION 14.353 | 67.28 units on a scale STANDARD_DEVIATION 12.715 | 64.48 units on a scale STANDARD_DEVIATION 11.407 | 66.05 units on a scale STANDARD_DEVIATION 12.841 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 11 Participants | 11 Participants | 34 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 31 Participants | 34 Participants | 33 Participants | 98 Participants |
| Region of Enrollment United States | 46 Participants | 46 Participants | 46 Participants | 138 Participants |
| Sex: Female, Male Female | 32 Participants | 34 Participants | 36 Participants | 102 Participants |
| Sex: Female, Male Male | 14 Participants | 12 Participants | 10 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 46 | 0 / 46 | 0 / 46 |
| other Total, other adverse events | 9 / 46 | 6 / 46 | 6 / 46 |
| serious Total, serious adverse events | 0 / 46 | 1 / 46 | 0 / 46 |
Outcome results
Primary
Corneal Fluorescein Staining
Mean change from baseline in zonal corneal fluorescein staining score in study eye using a 0- to 4-unit clinical grading scale, with 0 being better and 4 being worse
Time frame: 8 weeks
Population: mITT Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Vehicle Ophthalmic Solution | Corneal Fluorescein Staining | Zone 4 | -0.40 units on a scale | Standard Error 0.12 |
| Vehicle Ophthalmic Solution | Corneal Fluorescein Staining | Zone 3 | -0.44 units on a scale | Standard Error 0.09 |
| Vehicle Ophthalmic Solution | Corneal Fluorescein Staining | Zone 1 | -0.33 units on a scale | Standard Error 0.1 |
| Vehicle Ophthalmic Solution | Corneal Fluorescein Staining | Zone 2 | -0.31 units on a scale | Standard Error 0.08 |
| Vehicle Ophthalmic Solution | Corneal Fluorescein Staining | Zone 5 | -0.54 units on a scale | Standard Error 0.13 |
| ALY688 Ophthalmic Solution 0.1% | Corneal Fluorescein Staining | Zone 3 | -0.45 units on a scale | Standard Error 0.09 |
| ALY688 Ophthalmic Solution 0.1% | Corneal Fluorescein Staining | Zone 1 | -0.37 units on a scale | Standard Error 0.1 |
| ALY688 Ophthalmic Solution 0.1% | Corneal Fluorescein Staining | Zone 2 | -0.21 units on a scale | Standard Error 0.08 |
| ALY688 Ophthalmic Solution 0.1% | Corneal Fluorescein Staining | Zone 4 | -0.43 units on a scale | Standard Error 0.11 |
| ALY688 Ophthalmic Solution 0.1% | Corneal Fluorescein Staining | Zone 5 | -0.42 units on a scale | Standard Error 0.13 |
| ALY688 Ophthalmic Solution 0.4% | Corneal Fluorescein Staining | Zone 5 | -0.81 units on a scale | Standard Error 0.13 |
| ALY688 Ophthalmic Solution 0.4% | Corneal Fluorescein Staining | Zone 4 | -0.67 units on a scale | Standard Error 0.12 |
| ALY688 Ophthalmic Solution 0.4% | Corneal Fluorescein Staining | Zone 1 | -0.51 units on a scale | Standard Error 0.1 |
| ALY688 Ophthalmic Solution 0.4% | Corneal Fluorescein Staining | Zone 3 | -0.51 units on a scale | Standard Error 0.09 |
| ALY688 Ophthalmic Solution 0.4% | Corneal Fluorescein Staining | Zone 2 | -0.36 units on a scale | Standard Error 0.08 |
Primary
Eye Dryness Score (7-Day Average)
Mean change from baseline in eye dryness score (7-day average) using a 0- to 100-unit visual analog scale, with 0 being better and 100 being worse
Time frame: 8 weeks
Population: mITT Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Vehicle Ophthalmic Solution | Eye Dryness Score (7-Day Average) | -6.48 units on a scale | Standard Error 2.62 |
| ALY688 Ophthalmic Solution 0.1% | Eye Dryness Score (7-Day Average) | -5.66 units on a scale | Standard Error 2.62 |
| ALY688 Ophthalmic Solution 0.4% | Eye Dryness Score (7-Day Average) | -11.14 units on a scale | Standard Error 2.64 |
Primary
Number of Subjects With Adverse Events
Subjects reporting any treatment-emergent adverse events
Time frame: 8 weeks
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vehicle Ophthalmic Solution | Number of Subjects With Adverse Events | 13 Participants |
| ALY688 Ophthalmic Solution 0.1% | Number of Subjects With Adverse Events | 15 Participants |
| ALY688 Ophthalmic Solution 0.4% | Number of Subjects With Adverse Events | 10 Participants |
Secondary
Conjunctival Hyperemia Grading
Mean change from baseline in zonal conjunctival hyperemia in study eye using a 0- to 4-unit clinical grading scale and standardized grading photos, with 0 being better and 4 being worse
Time frame: 8 weeks
Population: mITT Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Vehicle Ophthalmic Solution | Conjunctival Hyperemia Grading | Temporal | -0.18 units on a scale | Standard Error 0.08 |
| Vehicle Ophthalmic Solution | Conjunctival Hyperemia Grading | Frontal | -0.17 units on a scale | Standard Error 0.07 |
| Vehicle Ophthalmic Solution | Conjunctival Hyperemia Grading | Nasal | -0.20 units on a scale | Standard Error 0.07 |
| ALY688 Ophthalmic Solution 0.1% | Conjunctival Hyperemia Grading | Nasal | -0.13 units on a scale | Standard Error 0.07 |
| ALY688 Ophthalmic Solution 0.1% | Conjunctival Hyperemia Grading | Temporal | -0.08 units on a scale | Standard Error 0.08 |
| ALY688 Ophthalmic Solution 0.1% | Conjunctival Hyperemia Grading | Frontal | -0.15 units on a scale | Standard Error 0.07 |
| ALY688 Ophthalmic Solution 0.4% | Conjunctival Hyperemia Grading | Frontal | -0.13 units on a scale | Standard Error 0.07 |
| ALY688 Ophthalmic Solution 0.4% | Conjunctival Hyperemia Grading | Temporal | -0.21 units on a scale | Standard Error 0.08 |
| ALY688 Ophthalmic Solution 0.4% | Conjunctival Hyperemia Grading | Nasal | -0.24 units on a scale | Standard Error 0.07 |
Secondary
Conjunctival Lissamine Green Staining
Mean change from baseline in zonal conjunctival lissamine green staining in study eye using a 0- to 4-unit clinical grading scale, with 0 being better and 4 being worse
Time frame: 8 weeks
Population: mITT Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Vehicle Ophthalmic Solution | Conjunctival Lissamine Green Staining | Zone 1 | 0.12 units on a scale | Standard Error 0.1 |
| Vehicle Ophthalmic Solution | Conjunctival Lissamine Green Staining | Zone 2 | -0.04 units on a scale | Standard Error 0.11 |
| Vehicle Ophthalmic Solution | Conjunctival Lissamine Green Staining | Zone 3 | 0.02 units on a scale | Standard Error 0.12 |
| Vehicle Ophthalmic Solution | Conjunctival Lissamine Green Staining | Zone 4 | -0.22 units on a scale | Standard Error 0.11 |
| Vehicle Ophthalmic Solution | Conjunctival Lissamine Green Staining | Zone 5 | -0.17 units on a scale | Standard Error 0.13 |
| Vehicle Ophthalmic Solution | Conjunctival Lissamine Green Staining | Zone 6 | 0.00 units on a scale | Standard Error 0.14 |
| ALY688 Ophthalmic Solution 0.1% | Conjunctival Lissamine Green Staining | Zone 6 | -0.02 units on a scale | Standard Error 0.13 |
| ALY688 Ophthalmic Solution 0.1% | Conjunctival Lissamine Green Staining | Zone 1 | -0.13 units on a scale | Standard Error 0.1 |
| ALY688 Ophthalmic Solution 0.1% | Conjunctival Lissamine Green Staining | Zone 4 | -0.37 units on a scale | Standard Error 0.11 |
| ALY688 Ophthalmic Solution 0.1% | Conjunctival Lissamine Green Staining | Zone 5 | -0.32 units on a scale | Standard Error 0.12 |
| ALY688 Ophthalmic Solution 0.1% | Conjunctival Lissamine Green Staining | Zone 2 | -0.25 units on a scale | Standard Error 0.11 |
| ALY688 Ophthalmic Solution 0.1% | Conjunctival Lissamine Green Staining | Zone 3 | -0.15 units on a scale | Standard Error 0.11 |
| ALY688 Ophthalmic Solution 0.4% | Conjunctival Lissamine Green Staining | Zone 2 | -0.31 units on a scale | Standard Error 0.11 |
| ALY688 Ophthalmic Solution 0.4% | Conjunctival Lissamine Green Staining | Zone 3 | -0.26 units on a scale | Standard Error 0.12 |
| ALY688 Ophthalmic Solution 0.4% | Conjunctival Lissamine Green Staining | Zone 6 | -0.15 units on a scale | Standard Error 0.14 |
| ALY688 Ophthalmic Solution 0.4% | Conjunctival Lissamine Green Staining | Zone 4 | -0.22 units on a scale | Standard Error 0.11 |
| ALY688 Ophthalmic Solution 0.4% | Conjunctival Lissamine Green Staining | Zone 1 | -0.18 units on a scale | Standard Error 0.1 |
| ALY688 Ophthalmic Solution 0.4% | Conjunctival Lissamine Green Staining | Zone 5 | -0.31 units on a scale | Standard Error 0.13 |
Secondary
Ocular Discomfort Score by Visual Analog Scale
Mean change from baseline in ocular discomfort score of 7-day average using a 0- to 100-unit visual analog scale, with 0 being better and 100 being worse
Time frame: 8 weeks
Population: Modified Intent-to-Treat (mITT) Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vehicle Ophthalmic Solution | Ocular Discomfort Score by Visual Analog Scale | -8.19 units on a scale | Standard Deviation 16.314 |
| ALY688 Ophthalmic Solution 0.1% | Ocular Discomfort Score by Visual Analog Scale | -4.47 units on a scale | Standard Deviation 17.31 |
| ALY688 Ophthalmic Solution 0.4% | Ocular Discomfort Score by Visual Analog Scale | -8.62 units on a scale | Standard Deviation 23.926 |
Secondary
Schirmer's Test
Mean change from baseline in tear volume in study eye as assessed by unanesthetized Schirmer test
Time frame: 8 weeks
Population: PP Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Vehicle Ophthalmic Solution | Schirmer's Test | 1.64 mm | Standard Error 0.94 |
| ALY688 Ophthalmic Solution 0.1% | Schirmer's Test | 1.92 mm | Standard Error 0.91 |
| ALY688 Ophthalmic Solution 0.4% | Schirmer's Test | 2.50 mm | Standard Error 0.93 |
Secondary
Symptom Assessment in Dry Eye (SAnDE) Score Assessment
Mean change from baseline in Symptom Assessment in Dry Eye global symptom score on a 0- to 100-unit visual analog scale, with 0 being better and 100 being worse. Global symptom score is calculated as the square root of the frequency score time the severity score per visit
Time frame: 8 weeks
Population: mITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vehicle Ophthalmic Solution | Symptom Assessment in Dry Eye (SAnDE) Score Assessment | -13.76 units on a scale | Standard Deviation 19.247 |
| ALY688 Ophthalmic Solution 0.1% | Symptom Assessment in Dry Eye (SAnDE) Score Assessment | -6.76 units on a scale | Standard Deviation 16.84 |
| ALY688 Ophthalmic Solution 0.4% | Symptom Assessment in Dry Eye (SAnDE) Score Assessment | -15.48 units on a scale | Standard Deviation 25.219 |
Secondary
Tear Film Break-up Time (TBUT)
Mean change from baseline in TBUT in study eye
Time frame: 8 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Vehicle Ophthalmic Solution | Tear Film Break-up Time (TBUT) | 0.29 seconds | Standard Error 0.26 |
| ALY688 Ophthalmic Solution 0.1% | Tear Film Break-up Time (TBUT) | 0.13 seconds | Standard Error 0.25 |
| ALY688 Ophthalmic Solution 0.4% | Tear Film Break-up Time (TBUT) | 0.18 seconds | Standard Error 0.26 |