Proof of Concept Study to Evaluate Safety and Efficacy of LME636 in the Treatment of Acute Anterior Uveitis

Study Overview
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Brief Summary
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The purpose of the study is to determine whether topical ocular administration of LME636 60 mg/mL is efficacious in resolving the ocular inflammation in the anterior chamber (AC) associated with acute anterior uveitis (AAU).

Detailed Description
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Eligible subjects will be randomized to LME636 or Dexamethasone in a 3:1 ratio at the time they present to the trial site with the AAU flare and will enter treatment for 28 full days. Subjects with worsening disease from Visit 2/Day 4 onward or subjects without improvement after 14 days of treatment will be discontinued from treatment, unmasked and treated with a rescue regimen at the discretion of the investigator.

Official Title
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A Multicenter, Randomized, Double-Masked, Active-Controlled Study to Evaluate the Safety and Efficacy of LME636 in Patients With Acute Anterior Uveitis

Conditions
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Acute Anterior Uveitis

Intervention / Treatment
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* Drug: LME636 60 mg/mL ophthalmic solution
* Drug: Dexamethasone 0.1% ophthalmic solution
* Drug: LME636 Vehicle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide written informed consent. Diagnosis of non-infectious AAU in at least 1 eye. Anterior chamber cell score of 2+ or 3+ as per Standardization of Uveitis Nomenclature (SUN) in at least one eye. Able to communicate well with the Investigator, to understand and comply with the requirements of the study. Other protocol-specified inclusion criteria may apply. Exclusion Criteria: Women of child-bearing potential unwilling to use effective contraception methods as defined in the protocol. AC cell score of 4+ (SUN) or hypopyon. Onset of anterior uveitis more than 2 weeks prior to enrollment in the study. Presence of intermediate-, posterior-, or panuveitis in either eye. Administration of stable doses >10 mg daily systemic prednisone or corticosteroids as described in the protocol. Recurrent corneal abrasion or ulceration in either eye (past or present). Tuberculosis (past or present). Other protocol-specified exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LME636<br>LME636 60 mg/mL ophthalmic solution, maximum drop frequency administered for 2 weeks, followed by a tapering for 1 week (Week 3) and 1 week of masked Vehicle administration (Week 4) | Drug: LME636 60 mg/mL ophthalmic solution<br> <br> Drug: LME636 Vehicle<br>* Inactive ingredients used for masking purposes<br>|
| Active Comparator: Dexamethasone<br>Dexamethasone 0.1% ophthalmic solution, maximum drop frequency administered for 2 weeks, followed by a tapering for 2 weeks (Weeks 3 and 4) | Drug: Dexamethasone 0.1% ophthalmic solution<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Responders at Day 15 | Response was defined as a two-step decrease or more from baseline in Anterior Chamber (AC) Cell Grade as per Standardization of Uveitis Nomenclature (SUN). Baseline was defined as the measurement taken before drug administration on Day 1. Subjects receiving rescue treatment on or before Day 15 were considered non-responders. Only one eye contributed to the analysis. | Baseline (Day 1), Day 15 | 
| Mean Best Corrected Visual Acuity (BCVA) at Each Visit | Visual Acuity (VA) with the subject's best spectacles or other visual corrective devices was measured using an Early Treatment of Diabetic Retinopathy Study (ETDRS) or Snellen visual acuity chart and reported in letters read correctly. An increase (gain) in letters read indicates improvement. Only one eye contributed to the analysis. | Baseline (Day 1), Day 4, Day 8, Day 15, Day 22, Day 29 | 
| Mean Intraocular Pressure (IOP) at Each Visit | IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry or Tonopen and reported in millimeters mercury (mmHg). A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). Only one eye contributed to the analysis. | Baseline (Day 1), Day 4, Day 8, Day 15, Day 22, Day 29 | 
| Number of Subjects With Increase From Baseline in Slit Lamp Parameters at Any Post-Treatment Visit | Slit-lamp biomicroscopy (examination) was performed to evaluate the anterior segment of the eye, including lids/lashes, conjunctiva, cornea, anterior chamber (cells and flare), iris, and lens. Ocular signs were categorized as Aqueous Flare, Aqueous Inflammatory Cell Grade, Keratic Precipitates, Lens, Limbal Injection, Status of Lens, Peripheral Anterior Synechia, and Posterior Synechia. An increase indicates worsening. Only one eye contributed to the analysis. | Baseline (Day 1), Day 4, Day 8, Day 15, Day 22, Day 29 | 
| Number of Subjects With an Increase From Baseline in Dilated Fundus Parameters at Any Post-Treatment Visit | The dilated fundus examination was performed to evaluate the health of the vitreous, optic disc, retinal vessels, macula, and retinal periphery. An increase indicates worsening. Only one eye contributed to the analysis. | Baseline (Day 1), Day 4, Day 8, Day 15, Day 22, Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With IOP Change From Baseline to Last On-Treatment Assessment | IOP was assessed using Goldmann applanation tonometry or Tonopen and reported in mmHg. A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). Only one eye contributed to the analysis. | Baseline (Day 1), Up to Day 29 | 
| Mean Change From Baseline in BCVA at Each Visit | Visual Acuity (VA) was measured with the participant's best spectacles or other visual corrective device in place using an ETDRS or Snellen visual acuity chart. Improvement of BCVA was defined as an increase (gain) in letters read from the baseline assessment. Only one eye contributed to the analysis. | Baseline (Day 1), Day 4, Day 8, Day 15, Day 22, Day 29 | 
| Time-to-Response | Time-to-Response was defined as the number of days from baseline to the first scheduled visit when a two-step decrease or more from baseline in AC Cell Grade (as per SUN) was observed. Time-to-Response is reported as number of subjects presenting time-to-response by visit. Only one eye contributed to the analysis. | Baseline (Day 1), Up to Day 15 | 
| Use of Rescue Treatment | Use of rescue treatment is presented as the number of subjects with first use of rescue treatment by visit. Subjects receiving rescue medication were not considered withdrawn and the collection of data continued after discontinuation of study treatment. Only one eye contributed to the analysis. | Day 4, Day 8, Day 15 | 
| Mean Serum Concentration of Total LME636 at Each Visit | Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. Concentrations below the limit of quantification (BLQ), defined as 0.25 ng/mL, were reported as NA with no imputation for missing data. | Baseline (Day 1), Day 4, Day 8, Day 15, Day 22, Day 29 | 
| Number of Subjects With Anti-LME636 Antibodies Present at Each Visit | Serum samples were collected and assessed for anti-LME636 antibodies. Samples collected from subjects in the LME636 dose group were analyzed for anti-LME636 antibodies. For subjects in the dexamethasone group, only the samples collected on Day 1 (ie, prior to the start of treatment) were analyzed for anti-LME636 antibodies. | Day 1, Day 4, Day 8, Day 15, Day 22, Day 29 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute anterior uveitis, LME636