Dry Eye, Meibomian Gland Dysfunction
Conditions
Brief summary
AZ201801 is a multicenter study of AZR-MD-001 ointment and AZR-MD-001 vehicle in patients with Meibomian Gland Dysfunction (MGD) and evaporative Dry Eye Disease (DED)
Detailed description
AZ201801 is a multicenter, double-masked, vehicle-controlled, randomized, parallel group study carried out in 2 sequentially overlapping cohorts evaluating the safety, efficacy and tolerability of AZR-MD-001 ointment and AZR-MD-001 vehicle in patients with Meibomian Gland Dysfunction (MGD) and evaporative Dry Eye Disease (DED)
Interventions
DRUGAZR-MD-001 Low Dose
AZR-MD-001 is an ophthalmic ointment
DRUGAZR-MD-001 Mid Dose
AZR-MD-001 is an ophthalmic ointment
DRUGAZR-MD-001 High Dose
AZR-MD-001 is an ophthalmic ointment
AZR-MD-001 is a vehicle ophthalmic ointment
Sponsors
Syneos Health
Cliantha Research
Azura Ophthalmics
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
* Male or female, 18 years of age or older * Best-corrected visual acuity (BCVA) of 20/40 or better (Snellen equivalent), using the logarithm of the minimum angle of resolution (LogMAR) in each eye * Evidence of meibomian gland obstruction * Reported dry eye signs and symptoms within the past 3 months
Exclusion criteria
* Uncontrolled ocular disease (except for MGD and dry eye disease/keratoconjunctivitis sicca) or uncontrolled systemic disease * Glaucoma, ocular hypertension, or intraocular pressure (IOP) in either eye at screening ≥24 mm Hg or has planned insertion/removal of glaucoma filtration shunts/devices during the study * Corneal abnormality or disorder that impacts normal spreading of the tear film or corneal integrity * BCVA worse than 20/40 in either eye * Current use of punctal plugs, anticipated insertion during the study, or a history of punctal cautery in either eye
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Meibomian Glands Yielding Liquid Secretion (MGYLS) | Value at month 3 minus value at baseline | Change from Baseline in MGYLS. The MGYLS can range from 0 (abnormal) to 15 (normal) |
| Ocular Surface Disease Index (OSDI) Total Score | Value at month 3 minus value at baseline | Change from Baseline in OSDI Total Score. The OSDI Total Score can range from 100 (highly abnormal) to 0 (Normal) |
Countries
Australia, Canada, New Zealand
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Stage 1: AZR-MD-001 Low Dose AZR-MD-001 Low Dose was dosed twice weekly.
AZR-MD-001 Low Dose: AZR-MD-001 is an ophthalmic ointment | 9 |
| Stage 1: AZR-MD-001 Mid Dose AZR-MD-001 Mid Dose was dosed twice weekly.
AZR-MD-001 Mid Dose: AZR-MD-001 is an ophthalmic ointment | 27 |
| Stage 1: AZR-MD-001 High Dose AZR-MD-001 High Dose was dosed twice weekly.
AZR-MD-001 High Dose: AZR-MD-001 is an ophthalmic ointment | 24 |
| Stage 1: AZR-MD-001 Vehicle AZR-MD-001 Vehicle was dosed twice weekly.
AZR-MD-001 Vehicle: AZR-MD-001 is a vehicle ophthalmic ointment | 16 |
| Stage 2: AZR-MD-001 Mid Dose AZR-MD-001 Mid Dose was dosed twice weekly.
AZR-MD-001 Mid Dose: AZR-MD-001 is an ophthalmic ointment | 82 |
| Stage 2: AZR-MD-001 High Dose AZR-MD-001 High Dose was dosed twice weekly.
AZR-MD-001 High Dose: AZR-MD-001 is an ophthalmic ointment | 83 |
| Stage 2: AZR-MD-001 Vehicle AZR-MD-001 Vehicle was dosed twice weekly.
AZR-MD-001 Vehicle: AZR-MD-001 is a vehicle ophthalmic ointment | 80 |
| Total | 321 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Stage 1 | Adverse Event | 0 | 5 | 7 | 1 |
| Stage 1 | Withdrawal by Subject | 0 | 0 | 1 | 0 |
| Stage 2 | Adverse Event | 0 | 2 | 1 | 0 |
| Stage 2 | Lost to Follow-up | 0 | 2 | 0 | 3 |
| Stage 2 | Protocol Violation | 0 | 1 | 6 | 0 |
| Stage 2 | Withdrawal by Subject | 0 | 11 | 9 | 3 |
Baseline characteristics
| Characteristic | Total | Stage 1: AZR-MD-001 Mid Dose | Stage 1: AZR-MD-001 High Dose | Stage 1: AZR-MD-001 Vehicle | Stage 1: AZR-MD-001 Low Dose | Stage 2: AZR-MD-001 Mid Dose | Stage 2: AZR-MD-001 High Dose | Stage 2: AZR-MD-001 Vehicle |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 53.2 years STANDARD_DEVIATION 17.5 | 42.1 years STANDARD_DEVIATION 17.71 | 45.6 years STANDARD_DEVIATION 22.02 | 43.6 years STANDARD_DEVIATION 20.34 | 51.2 years STANDARD_DEVIATION 18.79 | 52.1 years STANDARD_DEVIATION 16.9 | 55.6 years STANDARD_DEVIATION 17.2 | 51.9 years STANDARD_DEVIATION 18.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants | 3 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 305 Participants | 25 Participants | 22 Participants | 14 Participants | 9 Participants | 77 Participants | 80 Participants | 78 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants | 2 Participants | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Meibomian Glands Yielding Liquid Secretion (Primary Sign Endpoint) | 1.8 Gland Count (0 to 15) STANDARD_DEVIATION 1.3 | 2.8 Gland Count (0 to 15) STANDARD_DEVIATION 1.26 | 2.9 Gland Count (0 to 15) STANDARD_DEVIATION 1.49 | 2.8 Gland Count (0 to 15) STANDARD_DEVIATION 1.64 | 2.5 Gland Count (0 to 15) STANDARD_DEVIATION 0.58 | 1.7 Gland Count (0 to 15) STANDARD_DEVIATION 1.4 | 1.9 Gland Count (0 to 15) STANDARD_DEVIATION 1.4 | 1.8 Gland Count (0 to 15) STANDARD_DEVIATION 1.3 |
| OSDI Total Score (Primary Symptom Endpoint) | 24.8 Total Score (0 to 100) STANDARD_DEVIATION 6.7 | 23.1 Total Score (0 to 100) STANDARD_DEVIATION 6.1 | 21.34 Total Score (0 to 100) STANDARD_DEVIATION 4.86 | 22.64 Total Score (0 to 100) STANDARD_DEVIATION 7.57 | 25 Total Score (0 to 100) STANDARD_DEVIATION 7.42 | 25.2 Total Score (0 to 100) STANDARD_DEVIATION 7.5 | 24.2 Total Score (0 to 100) STANDARD_DEVIATION 6 | 25 Total Score (0 to 100) STANDARD_DEVIATION 6.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 77 Participants | 10 Participants | 8 Participants | 8 Participants | 4 Participants | 16 Participants | 10 Participants | 21 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 19 Participants | 2 Participants | 2 Participants | 2 Participants | 0 Participants | 6 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) White | 217 Participants | 15 Participants | 14 Participants | 6 Participants | 5 Participants | 57 Participants | 64 Participants | 56 Participants |
| Sex: Female, Male Female | 196 Participants | 11 Participants | 11 Participants | 5 Participants | 6 Participants | 51 Participants | 56 Participants | 56 Participants |
| Sex: Female, Male Male | 125 Participants | 16 Participants | 13 Participants | 11 Participants | 3 Participants | 31 Participants | 27 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 27 | 0 / 24 | 0 / 16 | 0 / 82 | 0 / 83 | 0 / 80 |
| other Total, other adverse events | 2 / 9 | 13 / 27 | 14 / 24 | 4 / 16 | 54 / 82 | 60 / 83 | 8 / 80 |
| serious Total, serious adverse events | 0 / 9 | 0 / 27 | 2 / 24 | 0 / 16 | 1 / 82 | 1 / 83 | 2 / 80 |
Outcome results
Primary
Meibomian Glands Yielding Liquid Secretion (MGYLS)
Change from Baseline in MGYLS. The MGYLS can range from 0 (abnormal) to 15 (normal)
Time frame: Value at month 3 minus value at baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stage 1: AZR-MD-001 Low Dose | Meibomian Glands Yielding Liquid Secretion (MGYLS) | -0.7 Number of Open Glands | Standard Deviation 1.56 |
| Stage 1: AZR-MD-001 Mid Dose | Meibomian Glands Yielding Liquid Secretion (MGYLS) | 3.41 Number of Open Glands | Standard Deviation 0.8 |
| Stage 1: AZR-MD-001 High Dose | Meibomian Glands Yielding Liquid Secretion (MGYLS) | 3.07 Number of Open Glands | Standard Deviation 0.81 |
| Stage 1: AZR-MD-001 Vehicle | Meibomian Glands Yielding Liquid Secretion (MGYLS) | 1.88 Number of Open Glands | Standard Deviation 1.38 |
| Stage 2: AZR-MD-001 Mid Dose | Meibomian Glands Yielding Liquid Secretion (MGYLS) | 4.2 Number of Open Glands | Standard Deviation 0.36 |
| Stage 2: AZR-MD-001 High Dose | Meibomian Glands Yielding Liquid Secretion (MGYLS) | 3.2 Number of Open Glands | Standard Deviation 0.4 |
| Stage 2: AZR-MD-001 Vehicle | Meibomian Glands Yielding Liquid Secretion (MGYLS) | 2.4 Number of Open Glands | Standard Deviation 0.34 |
Primary
Ocular Surface Disease Index (OSDI) Total Score
Change from Baseline in OSDI Total Score. The OSDI Total Score can range from 100 (highly abnormal) to 0 (Normal)
Time frame: Value at month 3 minus value at baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stage 1: AZR-MD-001 Low Dose | Ocular Surface Disease Index (OSDI) Total Score | 12.93 Scores on a Scale | Standard Deviation 4.62 |
| Stage 1: AZR-MD-001 Mid Dose | Ocular Surface Disease Index (OSDI) Total Score | -8.73 Scores on a Scale | Standard Deviation 2.37 |
| Stage 1: AZR-MD-001 High Dose | Ocular Surface Disease Index (OSDI) Total Score | -4.74 Scores on a Scale | Standard Deviation 2.41 |
| Stage 1: AZR-MD-001 Vehicle | Ocular Surface Disease Index (OSDI) Total Score | -2.34 Scores on a Scale | Standard Deviation 4.09 |
| Stage 2: AZR-MD-001 Mid Dose | Ocular Surface Disease Index (OSDI) Total Score | -7.29 Scores on a Scale | Standard Deviation 1.3 |
| Stage 2: AZR-MD-001 High Dose | Ocular Surface Disease Index (OSDI) Total Score | -6.1 Scores on a Scale | Standard Deviation 1.3 |
| Stage 2: AZR-MD-001 Vehicle | Ocular Surface Disease Index (OSDI) Total Score | -3.8 Scores on a Scale | Standard Deviation 1.2 |