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

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

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).

Study Overview

• Status: Completed
• Conditions: Acute Anterior Uveitis
• Intervention / Treatment: Drug: LME636 60 mg/mL ophthalmic solution; Drug: LME636 Vehicle; Drug: Dexamethasone 0.1% ophthalmic solution

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LME636; 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; Drug: LME636 Vehicle; Inactive ingredients used for masking purposes
Active Comparator: Dexamethasone; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Alcon Research
• Investigators: Study Director: Clinical Scientist NIBR, Alcon, Alcon Research

Study record dates

Study Major Dates

• Study Start (Actual): July 17, 2015
• Primary Completion (Actual): March 21, 2016
• Study Completion (Actual): March 21, 2016

Study Registration Dates

• First Submitted: June 23, 2015
• First Submitted That Met QC Criteria: June 25, 2015
• First Posted (Estimate): June 26, 2015

Study Record Updates

• Last Update Posted (Actual): July 2, 2018
• Last Update Submitted That Met QC Criteria: May 31, 2018
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: Acute anterior uveitis; LME636
• Additional Relevant MeSH Terms: Eye Diseases; Panuveitis; Uveal Diseases; Iris Diseases; Uveitis; Uveitis, Anterior; Iridocyclitis; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone; Ophthalmic Solutions; Pharmaceutical Solutions
• Other Study ID Numbers: LME636-2201