Back to resultsProof of Concept Study to Evaluate Safety and Efficacy of LME636 in the Treatment of Acute Anterior Uveitis
Primary Purpose
Acute Anterior Uveitis
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
LME636 60 mg/mL ophthalmic solution
Dexamethasone 0.1% ophthalmic solution
LME636 Vehicle
Sponsored by
About this trial
This is an interventional treatment trial for Acute Anterior Uveitis focused on measuring Acute anterior uveitis, LME636
Eligibility 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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
LME636
Dexamethasone
Arm Description
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)
Dexamethasone 0.1% ophthalmic solution, maximum drop frequency administered for 2 weeks, followed by a tapering for 2 weeks (Weeks 3 and 4)
Outcomes
Primary Outcome Measures
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.
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.
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.
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.
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02482129
Brief Title
Proof of Concept Study to Evaluate Safety and Efficacy of LME636 in the Treatment of Acute Anterior Uveitis
Official Title
A Multicenter, Randomized, Double-Masked, Active-Controlled Study to Evaluate the Safety and Efficacy of LME636 in Patients With Acute Anterior Uveitis
Study Type
Interventional
2. Study Status
Record Verification Date
July 2017
Overall Recruitment Status
Completed
Study Start Date
July 17, 2015 (Actual)
Primary Completion Date
March 21, 2016 (Actual)
Study Completion Date
March 21, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alcon Research
4. Oversight
Data Monitoring Committee
No
5. Study Description
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).
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Anterior Uveitis
Keywords
Acute anterior uveitis, LME636
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
45 (Actual)
8. Arms, Groups, and Interventions
Arm Title
LME636
Arm Type
Experimental
Arm Description
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)
Arm Title
Dexamethasone
Arm Type
Active Comparator
Arm Description
Dexamethasone 0.1% ophthalmic solution, maximum drop frequency administered for 2 weeks, followed by a tapering for 2 weeks (Weeks 3 and 4)
Intervention Type
Drug
Intervention Name(s)
LME636 60 mg/mL ophthalmic solution
Intervention Type
Drug
Intervention Name(s)
Dexamethasone 0.1% ophthalmic solution
Intervention Type
Drug
Intervention Name(s)
LME636 Vehicle
Intervention Description
Inactive ingredients used for masking purposes
Primary Outcome Measure Information:
Title
Number of Responders at Day 15
Description
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.
Time Frame
Baseline (Day 1), Day 15
Title
Mean Best Corrected Visual Acuity (BCVA) at Each Visit
Description
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.
Time Frame
Baseline (Day 1), Day 4, Day 8, Day 15, Day 22, Day 29
Title
Mean Intraocular Pressure (IOP) at Each Visit
Description
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.
Time Frame
Baseline (Day 1), Day 4, Day 8, Day 15, Day 22, Day 29
Title
Number of Subjects With Increase From Baseline in Slit Lamp Parameters at Any Post-Treatment Visit
Description
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.
Time Frame
Baseline (Day 1), Day 4, Day 8, Day 15, Day 22, Day 29
Title
Number of Subjects With an Increase From Baseline in Dilated Fundus Parameters at Any Post-Treatment Visit
Description
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.
Time Frame
Baseline (Day 1), Day 4, Day 8, Day 15, Day 22, Day 29
Secondary Outcome Measure Information:
Title
Number of Subjects With IOP Change From Baseline to Last On-Treatment Assessment
Description
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.
Time Frame
Baseline (Day 1), Up to Day 29
Title
Mean Change From Baseline in BCVA at Each Visit
Description
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.
Time Frame
Baseline (Day 1), Day 4, Day 8, Day 15, Day 22, Day 29
Title
Time-to-Response
Description
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.
Time Frame
Baseline (Day 1), Up to Day 15
Title
Use of Rescue Treatment
Description
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.
Time Frame
Day 4, Day 8, Day 15
Title
Mean Serum Concentration of Total LME636 at Each Visit
Description
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.
Time Frame
Baseline (Day 1), Day 4, Day 8, Day 15, Day 22, Day 29
Title
Number of Subjects With Anti-LME636 Antibodies Present at Each Visit
Description
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.
Time Frame
Day 1, Day 4, Day 8, Day 15, Day 22, Day 29
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Scientist NIBR, Alcon
Organizational Affiliation
Alcon Research
Official's Role
Study Director
12. IPD Sharing Statement
Learn more about this trial
Proof of Concept Study to Evaluate Safety and Efficacy of LME636 in the Treatment of Acute Anterior Uveitis
We'll reach out to this number within 24 hrs