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

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ClinicalTrials.gov Identifier: NCT02482129
Recruitment Status : Completed
First Posted : June 26, 2015
Results First Posted : August 28, 2017
Last Update Posted : July 2, 2018
Sponsor:
Information provided by (Responsible Party):
Alcon Research

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Acute Anterior Uveitis Drug: LME636 60 mg/mL ophthalmic solution Drug: Dexamethasone 0.1% ophthalmic solution Drug: LME636 Vehicle Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 45 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-Masked, Active-Controlled Study to Evaluate the Safety and Efficacy of LME636 in Patients With Acute Anterior Uveitis
Actual Study Start Date : July 17, 2015
Actual Primary Completion Date : March 21, 2016
Actual Study Completion Date : March 21, 2016

Resource links provided by the National Library of Medicine


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



Primary Outcome Measures :
  1. Number of Responders at Day 15 [ Time Frame: Baseline (Day 1), 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.

  2. Mean Best Corrected Visual Acuity (BCVA) at Each Visit [ Time Frame: Baseline (Day 1), Day 4, Day 8, Day 15, Day 22, Day 29 ]
    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.

  3. Mean Intraocular Pressure (IOP) at Each Visit [ Time Frame: Baseline (Day 1), Day 4, Day 8, Day 15, Day 22, Day 29 ]
    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.

  4. Number of Subjects With Increase From Baseline in Slit Lamp Parameters at Any Post-Treatment Visit [ Time Frame: Baseline (Day 1), Day 4, Day 8, Day 15, Day 22, Day 29 ]
    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.

  5. Number of Subjects With an Increase From Baseline in Dilated Fundus Parameters at Any Post-Treatment Visit [ Time Frame: Baseline (Day 1), Day 4, Day 8, Day 15, Day 22, Day 29 ]
    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.


Secondary Outcome Measures :
  1. Number of Subjects With IOP Change From Baseline to Last On-Treatment Assessment [ Time Frame: Baseline (Day 1), Up to Day 29 ]
    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.

  2. Mean Change From Baseline in BCVA at Each Visit [ Time Frame: Baseline (Day 1), Day 4, Day 8, Day 15, Day 22, Day 29 ]
    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.

  3. Time-to-Response [ Time Frame: Baseline (Day 1), Up to Day 15 ]
    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.

  4. Use of Rescue Treatment [ Time Frame: Day 4, Day 8, Day 15 ]
    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.

  5. Mean Serum Concentration of Total LME636 at Each Visit [ Time Frame: Baseline (Day 1), Day 4, Day 8, Day 15, Day 22, Day 29 ]
    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.

  6. Number of Subjects With Anti-LME636 Antibodies Present at Each Visit [ Time Frame: Day 1, Day 4, Day 8, Day 15, Day 22, Day 29 ]
    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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02482129


Sponsors and Collaborators
Alcon Research
Investigators
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Study Director: Clinical Scientist NIBR, Alcon Alcon Research
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Responsible Party: Alcon Research
ClinicalTrials.gov Identifier: NCT02482129    
Other Study ID Numbers: LME636-2201
First Posted: June 26, 2015    Key Record Dates
Results First Posted: August 28, 2017
Last Update Posted: July 2, 2018
Last Verified: July 2017
Keywords provided by Alcon Research:
Acute anterior uveitis
LME636
Additional relevant MeSH terms:
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Uveitis
Uveitis, Anterior
Iridocyclitis
Uveal Diseases
Eye Diseases
Panuveitis
Iris Diseases
Dexamethasone
Pharmaceutical Solutions
Ophthalmic Solutions
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents