Trial Outcomes & Findings for Phase 3 Study of OTX-101 in the Treatment of Keratoconjunctivitis Sicca (NCT NCT02688556)

NCT ID: NCT02688556

Last Updated: 2022-08-29

Results Overview

Percentage of Eyes with Increase from Baseline of ≥ 10 mm in Schirmer's Test Score

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

745 participants

Primary outcome timeframe

Baseline and 12 weeks

Results posted on

2022-08-29

Participant Flow

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.

Participant milestones

Participant milestones
Measure
OTX-101 0.09%
0.09% cyclosporine nanomicellar ophthalmic solution
Vehicle
vehicle of OTX-101
Overall Study
STARTED
372
373
Overall Study
COMPLETED
347
361
Overall Study
NOT COMPLETED
25
12

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Phase 3 Study of OTX-101 in the Treatment of Keratoconjunctivitis Sicca

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
OTX-101 0.09%
n=371 Participants
0.09% cyclosporine nanomicellar ophthalmic solution
Vehicle
n=373 Participants
vehicle of OTX-101
Total
n=744 Participants
Total of all reporting groups
Age, Continuous
58.4 years
STANDARD_DEVIATION 14.10 • n=5 Participants
59.5 years
STANDARD_DEVIATION 14.68 • n=7 Participants
59.0 years
STANDARD_DEVIATION 14.40 • n=5 Participants
Sex: Female, Male
Female
315 Participants
n=5 Participants
311 Participants
n=7 Participants
626 Participants
n=5 Participants
Sex: Female, Male
Male
56 Participants
n=5 Participants
62 Participants
n=7 Participants
118 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
1 Participants
n=5 Participants
0 Participants
n=7 Participants
1 Participants
n=5 Participants
Race (NIH/OMB)
Asian
11 Participants
n=5 Participants
12 Participants
n=7 Participants
23 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
1 Participants
n=7 Participants
1 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
41 Participants
n=5 Participants
45 Participants
n=7 Participants
86 Participants
n=5 Participants
Race (NIH/OMB)
White
310 Participants
n=5 Participants
305 Participants
n=7 Participants
615 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
8 Participants
n=5 Participants
10 Participants
n=7 Participants
18 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 12 weeks

Population: Intent to treat population

Percentage of Eyes with Increase from Baseline of ≥ 10 mm in Schirmer's Test Score

Outcome measures

Outcome measures
Measure
OTX-101 0.09%
n=371 Participants
0.09% cyclosporine nanomicellar ophthalmic solution
Vehicle
n=373 Participants
vehicle of OTX-101
Tear Production
16.6 Percentage of eyes
9.2 Percentage of eyes

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: Intent to treat population

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)

Outcome measures

Outcome measures
Measure
OTX-101 0.09%
n=371 Participants
0.09% cyclosporine nanomicellar ophthalmic solution
Vehicle
n=373 Participants
vehicle of OTX-101
Conjunctival Staining
-1.53 score on a scale
Standard Deviation 1.927
-1.16 score on a scale
Standard Deviation 2.2064

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: Intent to treat population

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.

Outcome measures

Outcome measures
Measure
OTX-101 0.09%
n=341 Participants
0.09% cyclosporine nanomicellar ophthalmic solution
Vehicle
n=373 Participants
vehicle of OTX-101
Central Corneal Staining
-0.28 score on a scale
Standard Deviation 0.533
-0.26 score on a scale
Standard Deviation 0.588

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: Intent to treat population

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: 1. frequency of dry and irritated eyes on a scale of 0 (rarely) to 100 (all the time); and 2. 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.

Outcome measures

Outcome measures
Measure
OTX-101 0.09%
n=371 Participants
0.09% cyclosporine nanomicellar ophthalmic solution
Vehicle
n=373 Participants
vehicle of OTX-101
Symptom Score
-18.8 score on a scale
Standard Deviation 24.08
-19.1 score on a scale
Standard Deviation 23.14

Adverse Events

OTX-101 0.09%

Serious events: 6 serious events
Other events: 130 other events
Deaths: 1 deaths

Vehicle

Serious events: 2 serious events
Other events: 66 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
OTX-101 0.09%
n=372 participants at risk
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
n=372 participants at risk
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%
General disorders
Death
0.27%
1/372 • Number of events 1 • 12 weeks
0.00%
0/372 • 12 weeks
Infections and infestations
Pneumonia
0.27%
1/372 • Number of events 1 • 12 weeks
0.00%
0/372 • 12 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant
0.27%
1/372 • Number of events 1 • 12 weeks
0.00%
0/372 • 12 weeks
Injury, poisoning and procedural complications
Subdural haematoma
0.27%
1/372 • Number of events 1 • 12 weeks
0.00%
0/372 • 12 weeks
Musculoskeletal and connective tissue disorders
Spinal column stenosis
0.27%
1/372 • Number of events 1 • 12 weeks
0.00%
0/372 • 12 weeks
Renal and urinary disorders
Nephrolithiasis
0.27%
1/372 • Number of events 1 • 12 weeks
0.00%
0/372 • 12 weeks
General disorders
Perforated ulcer
0.00%
0/372 • 12 weeks
0.27%
1/372 • Number of events 1 • 12 weeks
Musculoskeletal and connective tissue disorders
Spinal osteoarthritis
0.00%
0/372 • 12 weeks
0.27%
1/372 • Number of events 1 • 12 weeks

Other adverse events

Other adverse events
Measure
OTX-101 0.09%
n=372 participants at risk
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
n=372 participants at risk
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%
Eye disorders
Conjunctival hyperaemia
8.1%
30/372 • 12 weeks
4.8%
18/372 • 12 weeks
Eye disorders
Blepharitis
1.3%
5/372 • 12 weeks
0.00%
0/372 • 12 weeks
Eye disorders
Eye irritation
0.81%
3/372 • 12 weeks
1.3%
5/372 • 12 weeks
Eye disorders
Eye pruritus
0.27%
1/372 • 12 weeks
1.3%
5/372 • 12 weeks
General disorders
Instillation site pain
24.2%
90/372 • 12 weeks
4.3%
16/372 • 12 weeks
General disorders
Instillation site lacrimation
1.1%
4/372 • 12 weeks
0.00%
0/372 • 12 weeks
Eye disorders
Instillation site reaction
1.1%
4/372 • 12 weeks
0.54%
2/372 • 12 weeks
Eye disorders
Sinusitis
1.1%
4/372 • 12 weeks
1.3%
5/372 • 12 weeks
Eye disorders
Urinary tract infection
1.1%
4/372 • 12 weeks
0.54%
2/372 • 12 weeks
Nervous system disorders
Headache
1.6%
6/372 • 12 weeks
0.54%
2/372 • 12 weeks
Eye disorders
Foreign body sensation in eyes
0.27%
1/372 • 12 weeks
1.3%
5/372 • 12 weeks
Eye disorders
Conjunctival haemorrhage
0.54%
2/372 • 12 weeks
0.27%
1/372 • 12 weeks
Eye disorders
Posterior capsule opacification
0.54%
2/372 • 12 weeks
0.54%
2/372 • 12 weeks
Eye disorders
Punctate keratitis
0.54%
2/372 • 12 weeks
0.81%
3/372 • 12 weeks

Additional Information

SPARC

Sun Pharma Advanced Research Company Limited

Phone: +912266455645

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place