NCT02365519

LME636 in the Relief of Persistent Ocular Discomfort in Subjects With Severe Dry Eye Disease

Completed Phase 2 Results posted Last updated 2 July 2018

What this trial tests

Phase 2 trial testing LME636 ophthalmic solution in Dry Eye in 514 participants. Completed in 16 October 2015.

Timeline

9 March 2015

Primary endpoint
16 October 2015

16 October 2015

Quick facts

Lead sponsor	Alcon, a Novartis Company
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	514
Start date	9 March 2015
Primary completion	16 October 2015
Estimated completion	16 October 2015

Drugs / interventions tested

• LME636 ophthalmic solution — full drug profile →
• LME636 Vehicle — full drug profile →

Conditions studied

• Dry Eye — all drugs for Dry Eye →

Sponsor

Alcon, a Novartis Company — full company profile →

Who can join

18 and older, any sex, with Dry Eye. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Mean Change From Baseline in Global Ocular Discomfort Score at Day 71 Primary · Baseline (Day 43), Day 71

Discomfort frequency and severity (each graded on a separate 100-units scale) were assessed daily using a visual analog scale (VAS) displayed on a handheld digital Pad (electronic patient-reported outcome (ePRO)). Frequency score was in response to the question 'how often your eyes felt uncomfortable during the past 24 hours' ranging from 'Rarely' to 'All the time.' Severity score was in response to the question 'how uncomfortable your eyes felt during the past 24 hours' ranging from 'Very mildly uncomfortable' to 'Very severely uncomfortable.' The Global Ocular Discomfort Score, ranging from

Group	Value	95% CI
LME636	-7.9	± 1.45
Vehicle	-3.6	± 1.49

Best Corrected Visual Acuity (BCVA) Primary · Baseline (Day 43), Day 57, Day 71, Day 85

Visual Acuity (VA) with the subject's best spectacles or other visual corrective devices was measured using an ETDRS visual acuity chart at 3 meters (10 feet) and reported in letters read correctly. An increase (gain) in letters read indicates improvement. Both eyes contributed to the analysis.

Baseline (Day 43)

Group	Value	95% CI
LME636	80.6	± 6.44
Vehicle	81.5	± 5.72

Day 57

Group	Value	95% CI
LME636	80.5	± 6.82
Vehicle	81.6	± 5.48

Day 71

Group	Value	95% CI
LME636	81.6	± 5.56
Vehicle	81.9	± 5.89

Day 85

Group	Value	95% CI
LME636	81.0	± 5.73
Vehicle	81.6	± 6.17

Intraocular Pressure (IOP) Primary · Baseline (Day 43), Day 57, Day 71, Day 85

IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry or Tonopen and measured in millimeters of mercury (mmHg). A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). Both eyes contributed to the analysis.

Baseline (Day 43)

Group	Value	95% CI
LME636	14.8	± 2.71
Vehicle	14.3	± 2.63

Day 57

Group	Value	95% CI
LME636	14.6	± 2.72
Vehicle	14.1	± 2.92

Day 71

Group	Value	95% CI
LME636	14.0	± 3.06
Vehicle	14.1	± 2.70

Day 85

Group	Value	95% CI
LME636	14.4	± 2.68
Vehicle	14.6	± 2.58

Percentage of Subjects With Increase in Slit-Lamp Parameter From Baseline to Any Visit Primary · Baseline (Day 43), Day 57, Day 71, Day 85

Ocular signs (cornea, lens, and iris/anterior chamber) were assessed by slit-lamp biomicroscopy. An increase indicates worsening. Only one eye contributed to the analysis.

Cornea

Group	Value	95% CI
LME636	0.0
Vehicle	0.0

Lens

Group	Value	95% CI
LME636	0.0
Vehicle	0.0

Iris

Group	Value	95% CI
LME636	0.0
Vehicle	0.0

Anterior Chamber

Group	Value	95% CI
LME636	0.0
Vehicle	0.0

Percentage of Subjects With Increase in Dilated Fundus Parameter From Baseline to Any Visit Primary · Baseline (Day 43), Day 57, Day 71, Day 85

The dilated fundus examination was performed to evaluate the health of the vitreous, retina, macula, choroid, and optic nerve. An increase indicates worsening. Only one eye contributed to the analysis.

Vitreous

Group	Value	95% CI
LME636	1.4
Vehicle	1.5

Retina

Group	Value	95% CI
LME636	1.4
Vehicle	0.0

Macula

Group	Value	95% CI
LME636	0.0
Vehicle	0.0

Choroid

Group	Value	95% CI
LME636	0.0
Vehicle	0.0

Optic Nerve

Group	Value	95% CI
LME636	0.0
Vehicle	0.0

Percentage of Subjects With More Than 20 Units Improvement in Global Ocular Discomfort Score From Baseline at Day 71 Secondary · Baseline (Day 43), Day 71

Discomfort frequency and severity (each graded on a separate 100-units scale) were assessed daily using a VAS displayed on a handheld ePRO. Frequency score was in response to the question 'how often your eyes felt uncomfortable during the past 24 hours' ranging from 'Rarely' to 'All the time.' Severity score was in response to the question 'how uncomfortable your eyes felt during the past 24 hours' ranging from 'Very mildly uncomfortable' to 'Very severely uncomfortable.' The Global Ocular Discomfort Score, ranging from 0 to 100, was calculated for any given day, as the square root of the prod

Group	Value	95% CI
LME636	17.9
Vehicle	4.7

Percentage of Subjects With LME636 Serum Concentrations Below the Lower Limit of Quantification (LLOQ) Secondary · Day 15, Day 29, Day 43, Day 57, Day 71, Day 85

Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. LLOQ is defined as 0.25 ng/mL.

Day 15

Group	Value	95% CI
LME636	100.0

Day 29

Group	Value	95% CI
LME636	100.0

Day 43 (prior to administration of first dose)

Group	Value	95% CI
LME636	98.5

Day 57

Group	Value	95% CI
LME636	82.1

Day 71

Group	Value	95% CI
LME636	71.9

Day 85 (last day of dosing)

Group	Value	95% CI
LME636	67.9

Percentage of Subjects With Anti-LME636 Antibodies by Visit Secondary · Day 15, Day 29, Day 43, Day 57, Day 71, Day 85

Samples were collected and assessed for anti-LME636 antibodies.

Day 15

Group	Value	95% CI
LME636	33.3
Vehicle	40.0
Run-In Only	26.9

Day 29

Group	Value	95% CI
LME636	37.3
Vehicle	37.7
Run-In Only	27.0

Day 43 (prior to administration of first dose)

Group	Value	95% CI
LME636	31.9
Vehicle	34.9
Run-In Only	27.0

Day 57 (Treatment Day 15)

Group	Value	95% CI
LME636	45.6
Vehicle	41.1

Day 71

Group	Value	95% CI
LME636	79.3
Vehicle	41.7

Day 85 (last day of dosing)

Group	Value	95% CI
LME636	86.8
Vehicle	40.4

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events (AEs) were collected from time of informed consent for the duration of a subject's participation in the study (up to 85 days).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Vehicle Run-In

Serious: 1/213 (0%)

Deaths: 0/213

LME636

Serious: 0/69 (0%)

Deaths: 0/69

Vehicle

Serious: 1/65 (2%)

Deaths: 0/65

Serious adverse events (2 terms)

Reaction	System	Vehicle Run-In	LME636	Vehicle
Extradural abscess	Infections and infestations	—	—	—
Pneumonia	Infections and infestations	—	—	—

Most-reported serious reactions: Extradural abscess, Pneumonia.

Data from ClinicalTrials.gov NCT02365519 adverse events section.

Sponsor's own description

The purpose of this study is to evaluate the efficacy of LME636 compared to vehicle in the reduction of ocular symptoms and to evaluate the safety and tolerability of LME636, when administered topically for up to 42 days, in subjects with severe dry eye disease.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Topical Anti-TNFα Agent Licaminlimab (OCS-02) Relieves Persistent Ocular Discomfort in Severe Dry Eye Disease: A Randomized Phase II Study.
   Shettle L, McLaurin E, Martel J, Seaman JW, et al · · 2022 · cited 11× · PMID 35821785 · DOI 10.2147/opth.s366836
2. Pharmacogenomic Analysis of Response to Topical Tumor Necrosis Factor α Antagonist Licaminlimab (OCS-02) in Dry Eye Disease [RETRACTED].
   · 2024 · cited 2× · PMID 38416549 · DOI 10.1097/ico.0000000000003510