Emerald: Phase 3 Study of OTX-101 in the Treatment of Keratoconjunctivitis Sicca
Study Details
Study Description
Brief Summary
This is a randomized, double-masked, vehicle-controlled study of the safety and efficacy of OTX-101 (0.09% cyclosporine nanomicellar solution) in the treatment of keratoconjunctivitis sicca to be conducted at approximately 50 sites.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: OTX-101 0.09% 0.09% cyclosporine nanomicellar ophthalmic solution |
Drug: cyclosporine
Other Names:
|
Placebo Comparator: Vehicle vehicle of OTX-101 |
Drug: vehicle of OTX-101
|
Outcome Measures
Primary Outcome Measures
- Tear Production [Baseline and 12 weeks]
Percentage of Eyes with Increase from Baseline of ≥ 10 mm in Schirmer's Test Score
Secondary Outcome Measures
- Conjunctival Staining [Baseline and 12 weeks]
change from baseline in total conjunctival staining score (lissamine green, modified National Eye Institute scale) at 12 weeks. Conjunctival Lissamine Green Staining Grades ranged from 0 (No punctate stain in zone) to 3 (Densely concentrated micropunctate stain spots)
- Central Corneal Staining [Baseline and 12 weeks]
change from baseline in central corneal staining score (fluorescein, modified NEI/FDA scale) at 12 weeks. The Expanded National Eye Institute (NEI)/Industry Workshop Scale for Corneal Staining Score was used to grade each of the 5 areas of the cornea on a 0 (No punctate stain in area) to 4 (Severe diffuse (coalescent) macropunctate stain of the area) scale.
- Symptom Score [Baseline and 12 weeks]
change from baseline in modified Symptom Assessment in Dry Eye (SANDE) score at 12 weeks. A modified SANDE instrument was used to evaluate dry eye symptoms at each visit. Subjects were asked to indicate: frequency of dry and irritated eyes on a scale of 0 (rarely) to 100 (all the time); and severity of dry eyes on a scale of 0 (very mild) to 100 (severe) The global symptom score is the square root of the frequency score times the severity score and will be completed at each visit. (range 0 to 100) Negative change from baseline indicates improvement.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
History of dry eye syndrome (KCS) for a period of at least 6 months
-
Clinical diagnosis of bilateral KCS
-
Lissamine green conjunctival staining sum score of ≥ 3 to ≤ 9 out of a total possible score of 12 (scoring excludes superior zones 2 and 4) in the same eye at both the Screening and Baseline Visits.
-
Global symptom score (SANDE) ≥ 40 mm at both the Screening and Baseline Visits
-
Corrected Snellen visual acuity (VA) of better than 20/200 in each eye.
Exclusion Criteria:
-
Use of cyclosporine ophthalmic emulsion 0.05% (Restasis®) within 3 months prior to the Screening Visit.
-
Previous treatment failure (lack of efficacy) with cyclosporine ophthalmic emulsion 0.05% (Restasis).
-
Diagnosis of Sjögren's disease ˃ 5 years prior to the Screening Visit.
-
Clinical diagnosis or any history of seasonal and/or perennial allergic conjunctivitis.
-
Use of systemic or topical medications within 7 days prior to the Screening Visit or during the study period that are known to cause dry eye.
-
Use of any topical ophthalmic medications, prescription (including anti-glaucoma medications) or over the counter (including artificial tears), other than the assigned study medication during the study period.
-
Current active eye disease other than dry wyw syndrome (i.e., any disease for which topical or systemic ophthalmic medication is necessary).
-
History of herpes keratitis.
-
Corneal transplant
-
Corneal refractive surgery within 6 months prior to the Screening Visit or postoperative refractive surgery symptoms of dryness that have not resolved.
-
Cataract surgery within 3 months prior to the Screening Visit.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Martel Eye Medical Group | Rancho Cordova | California | United States | 95670 |
2 | Cincinnati Eye Institute | Edgewood | Kentucky | United States | 41017 |
3 | Fifth Avenue Eye Associates | New York | New York | United States | 10028 |
Sponsors and Collaborators
- Sun Pharmaceutical Industries Limited
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- OTX-101-2016-001
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail | One subject in OTX-101 0.09% group, was never treated with study medication and is not included in any of analysis sets Additionally, because the subjects in the ITT analysis set were analyzed as randomized, one subject who erroneously received OTX-101 0.09%, was included in the Vehicle group for purposes of efficacy analysis. |
Arm/Group Title | OTX-101 0.09% | Vehicle |
---|---|---|
Arm/Group Description | 0.09% cyclosporine nanomicellar ophthalmic solution | vehicle of OTX-101 |
Period Title: Overall Study | ||
STARTED | 372 | 373 |
COMPLETED | 347 | 361 |
NOT COMPLETED | 25 | 12 |
Baseline Characteristics
Arm/Group Title | OTX-101 0.09% | Vehicle | Total |
---|---|---|---|
Arm/Group Description | 0.09% cyclosporine nanomicellar ophthalmic solution | vehicle of OTX-101 | Total of all reporting groups |
Overall Participants | 371 | 373 | 744 |
Age (years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [years] |
58.4
(14.10)
|
59.5
(14.68)
|
59.0
(14.40)
|
Sex: Female, Male (Count of Participants) | |||
Female |
315
84.9%
|
311
83.4%
|
626
84.1%
|
Male |
56
15.1%
|
62
16.6%
|
118
15.9%
|
Race (NIH/OMB) (Count of Participants) | |||
American Indian or Alaska Native |
1
0.3%
|
0
0%
|
1
0.1%
|
Asian |
11
3%
|
12
3.2%
|
23
3.1%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
1
0.3%
|
1
0.1%
|
Black or African American |
41
11.1%
|
45
12.1%
|
86
11.6%
|
White |
310
83.6%
|
305
81.8%
|
615
82.7%
|
More than one race |
8
2.2%
|
10
2.7%
|
18
2.4%
|
Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
Title | Tear Production |
---|---|
Description | Percentage of Eyes with Increase from Baseline of ≥ 10 mm in Schirmer's Test Score |
Time Frame | Baseline and 12 weeks |
Outcome Measure Data
Analysis Population Description |
---|
Intent to treat population |
Arm/Group Title | OTX-101 0.09% | Vehicle |
---|---|---|
Arm/Group Description | 0.09% cyclosporine nanomicellar ophthalmic solution | vehicle of OTX-101 |
Measure Participants | 371 | 373 |
Number [Percentage of eyes] |
16.6
|
9.2
|
Title | Conjunctival Staining |
---|---|
Description | change from baseline in total conjunctival staining score (lissamine green, modified National Eye Institute scale) at 12 weeks. Conjunctival Lissamine Green Staining Grades ranged from 0 (No punctate stain in zone) to 3 (Densely concentrated micropunctate stain spots) |
Time Frame | Baseline and 12 weeks |
Outcome Measure Data
Analysis Population Description |
---|
Intent to treat population |
Arm/Group Title | OTX-101 0.09% | Vehicle |
---|---|---|
Arm/Group Description | 0.09% cyclosporine nanomicellar ophthalmic solution | vehicle of OTX-101 |
Measure Participants | 371 | 373 |
Mean (Standard Deviation) [score on a scale] |
-1.53
(1.927)
|
-1.16
(2.2064)
|
Title | Central Corneal Staining |
---|---|
Description | change from baseline in central corneal staining score (fluorescein, modified NEI/FDA scale) at 12 weeks. The Expanded National Eye Institute (NEI)/Industry Workshop Scale for Corneal Staining Score was used to grade each of the 5 areas of the cornea on a 0 (No punctate stain in area) to 4 (Severe diffuse (coalescent) macropunctate stain of the area) scale. |
Time Frame | Baseline and 12 weeks |
Outcome Measure Data
Analysis Population Description |
---|
Intent to treat population |
Arm/Group Title | OTX-101 0.09% | Vehicle |
---|---|---|
Arm/Group Description | 0.09% cyclosporine nanomicellar ophthalmic solution | vehicle of OTX-101 |
Measure Participants | 341 | 373 |
Mean (Standard Deviation) [score on a scale] |
-0.28
(0.533)
|
-0.26
(0.588)
|
Title | Symptom Score |
---|---|
Description | change from baseline in modified Symptom Assessment in Dry Eye (SANDE) score at 12 weeks. A modified SANDE instrument was used to evaluate dry eye symptoms at each visit. Subjects were asked to indicate: frequency of dry and irritated eyes on a scale of 0 (rarely) to 100 (all the time); and severity of dry eyes on a scale of 0 (very mild) to 100 (severe) The global symptom score is the square root of the frequency score times the severity score and will be completed at each visit. (range 0 to 100) Negative change from baseline indicates improvement. |
Time Frame | Baseline and 12 weeks |
Outcome Measure Data
Analysis Population Description |
---|
Intent to treat population |
Arm/Group Title | OTX-101 0.09% | Vehicle |
---|---|---|
Arm/Group Description | 0.09% cyclosporine nanomicellar ophthalmic solution | vehicle of OTX-101 |
Measure Participants | 371 | 373 |
Mean (Standard Deviation) [score on a scale] |
-18.8
(24.08)
|
-19.1
(23.14)
|
Adverse Events
Time Frame | 12 weeks | |||
---|---|---|---|---|
Adverse Event Reporting Description | ||||
Arm/Group Title | OTX-101 0.09% | Vehicle | ||
Arm/Group Description | 0.09% cyclosporine nanomicellar ophthalmic solution. A total of 744 subjects were included in the Safety population, with 372 subjects in the OTX-101 0.09% group and 372 subjects in the Vehicle group. The only difference between the ITT and the Safety populations is that Subject 14-003 was analyzed in the Safety population according to the treatment received, which was OTX-101 0.09% | vehicle of OTX-101 A total of 744 subjects were included in the Safety population, with 372 subjects in the OTX-101 0.09% group and 372 subjects in the Vehicle group. The only difference between the ITT and the Safety populations is that Subject 14-003 was analyzed in the Safety population according to the treatment received, which was OTX-101 0.09% | ||
All Cause Mortality |
||||
OTX-101 0.09% | Vehicle | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 1/372 (0.3%) | 0/372 (0%) | ||
Serious Adverse Events |
||||
OTX-101 0.09% | Vehicle | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 6/372 (1.6%) | 2/372 (0.5%) | ||
General disorders | ||||
Death | 1/372 (0.3%) | 1 | 0/372 (0%) | 0 |
Perforated ulcer | 0/372 (0%) | 0 | 1/372 (0.3%) | 1 |
Infections and infestations | ||||
Pneumonia | 1/372 (0.3%) | 1 | 0/372 (0%) | 0 |
Injury, poisoning and procedural complications | ||||
Subdural haematoma | 1/372 (0.3%) | 1 | 0/372 (0%) | 0 |
Musculoskeletal and connective tissue disorders | ||||
Spinal column stenosis | 1/372 (0.3%) | 1 | 0/372 (0%) | 0 |
Spinal osteoarthritis | 0/372 (0%) | 0 | 1/372 (0.3%) | 1 |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
Lung neoplasm malignant | 1/372 (0.3%) | 1 | 0/372 (0%) | 0 |
Renal and urinary disorders | ||||
Nephrolithiasis | 1/372 (0.3%) | 1 | 0/372 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
OTX-101 0.09% | Vehicle | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 130/372 (34.9%) | 66/372 (17.7%) | ||
Eye disorders | ||||
Conjunctival hyperaemia | 30/372 (8.1%) | 18/372 (4.8%) | ||
Blepharitis | 5/372 (1.3%) | 0/372 (0%) | ||
Eye irritation | 3/372 (0.8%) | 5/372 (1.3%) | ||
Eye pruritus | 1/372 (0.3%) | 5/372 (1.3%) | ||
Instillation site reaction | 4/372 (1.1%) | 2/372 (0.5%) | ||
Sinusitis | 4/372 (1.1%) | 5/372 (1.3%) | ||
Urinary tract infection | 4/372 (1.1%) | 2/372 (0.5%) | ||
Foreign body sensation in eyes | 1/372 (0.3%) | 5/372 (1.3%) | ||
Conjunctival haemorrhage | 2/372 (0.5%) | 1/372 (0.3%) | ||
Posterior capsule opacification | 2/372 (0.5%) | 2/372 (0.5%) | ||
Punctate keratitis | 2/372 (0.5%) | 3/372 (0.8%) | ||
General disorders | ||||
Instillation site pain | 90/372 (24.2%) | 16/372 (4.3%) | ||
Instillation site lacrimation | 4/372 (1.1%) | 0/372 (0%) | ||
Nervous system disorders | ||||
Headache | 6/372 (1.6%) | 2/372 (0.5%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | SPARC |
---|---|
Organization | Sun Pharma Advanced Research Company Limited |
Phone | +912266455645 |
clinical.trials@sparcmail.com |
- OTX-101-2016-001