Trial Outcomes & Findings for Safety and Efficacy of Dexamethasone Ophthalmic Insert (Dextenza®) in the Management of Clinically Significant Dry Eye (NCT NCT04498468)
NCT ID: NCT04498468
Last Updated: 2024-03-15
Results Overview
OSS will be graded according to the Sjögren's International Collaborative Clinical Alliance (SICCA) grading system. Maximum possible fluorescein score (the punctate epithelial erosions grade + any extra points for modifiers \[central staining, confluent staining, and filaments\]) will be 6 and minimum of 0. Maximum possible conjunctival staining score (the punctate epithelial erosions grade on the temporal and nasal sides) will be 6 and minimum of 0. The total possible maximum OSS, derived by summing the corneal and conjunctival scores, will be 12 for each eye, and minimum OSS will be 0. Higher corneal, conjunctival, and staining scores represent worse outcomes. The difference between the average corneal staining in the treated arm versus the average corneal staining in the sham arm will be compared statistically.
Recruitment status
TERMINATED
Study phase
PHASE4
Target enrollment
77 participants
Primary outcome timeframe
28 days
Results posted on
2024-03-15
Participant Flow
Single-center, participant- and outcome assessor-masked, randomized controlled trial at the Ocular Surface Disease Clinic of Wilmer Eye Institute, The Johns Hopkins University School of Medicine in Baltimore, Maryland, USA.
Unit of analysis: eyes
Participant milestones
| Measure |
All Study Participants
All participants received treatment and control.
Treatment:
Commercially available Sustained Release Dexamethasone, 0.4 mg intracannalicular insert (DEXTENZA® - Ocular Therapeutix, Bedford, MA) Sustained Release Dexamethasone, 0.4 mg: dexamethasone 0.4mg lacrimal insert
Control:
FCIProlong® made of E-Caprolactone-L-Lactide copolymer (PCL) (FCI Ophthalmics Inc., Pembroke, MA) E-Caprolactone-L-Lactide copolymer (PCL) punctal plug: Control eye will receive a tear duct plug without the dexamethasone (EXTENDED WEAR SYNTHETIC ABSORBABLE PUNCTAL PLUG made of E-Caprolactone-L-Lactide copolymer (PCL). Absorbs in 60 to 180 days. Size 0.5mm which is comparable to the study treatment)
|
|---|---|
|
Overall Study
STARTED
|
77 154
|
|
Overall Study
COMPLETED
|
74 148
|
|
Overall Study
NOT COMPLETED
|
3 6
|
Reasons for withdrawal
| Measure |
All Study Participants
All participants received treatment and control.
Treatment:
Commercially available Sustained Release Dexamethasone, 0.4 mg intracannalicular insert (DEXTENZA® - Ocular Therapeutix, Bedford, MA) Sustained Release Dexamethasone, 0.4 mg: dexamethasone 0.4mg lacrimal insert
Control:
FCIProlong® made of E-Caprolactone-L-Lactide copolymer (PCL) (FCI Ophthalmics Inc., Pembroke, MA) E-Caprolactone-L-Lactide copolymer (PCL) punctal plug: Control eye will receive a tear duct plug without the dexamethasone (EXTENDED WEAR SYNTHETIC ABSORBABLE PUNCTAL PLUG made of E-Caprolactone-L-Lactide copolymer (PCL). Absorbs in 60 to 180 days. Size 0.5mm which is comparable to the study treatment)
|
|---|---|
|
Overall Study
Lost to Follow-up
|
3
|
Baseline Characteristics
Safety and Efficacy of Dexamethasone Ophthalmic Insert (Dextenza®) in the Management of Clinically Significant Dry Eye
Baseline characteristics by cohort
| Measure |
All Study Participants
n=150 eyes
All participants received treatment and control.
Treatment:
Commercially available Sustained Release Dexamethasone, 0.4 mg intracannalicular insert (DEXTENZA® - Ocular Therapeutix, Bedford, MA) Sustained Release Dexamethasone, 0.4 mg: dexamethasone 0.4mg lacrimal insert
Control:
FCIProlong® made of E-Caprolactone-L-Lactide copolymer (PCL) (FCI Ophthalmics Inc., Pembroke, MA) E-Caprolactone-L-Lactide copolymer (PCL) punctal plug: Control eye will receive a tear duct plug without the dexamethasone (EXTENDED WEAR SYNTHETIC ABSORBABLE PUNCTAL PLUG made of E-Caprolactone-L-Lactide copolymer (PCL). Absorbs in 60 to 180 days. Size 0.5mm which is comparable to the study treatment)
|
|---|---|
|
Age, Customized
Age Categories of Participants · 18-29 years
|
2 Participants
n=5 Participants
|
|
Age, Customized
Age Categories of Participants · 30-39 years
|
8 Participants
n=5 Participants
|
|
Age, Customized
Age Categories of Participants · 40-49 years
|
10 Participants
n=5 Participants
|
|
Age, Customized
Age Categories of Participants · 50-59 years
|
19 Participants
n=5 Participants
|
|
Age, Customized
Age Categories of Participants · 60-69 years
|
23 Participants
n=5 Participants
|
|
Age, Customized
Age Categories of Participants · 70-79 years
|
12 Participants
n=5 Participants
|
|
Age, Customized
Age Categories of Participants · 80 years or older
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
65 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
6 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
10 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
55 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=5 Participants
|
|
Posterior Blepharitis
Yes
|
69 Participants
n=5 Participants
|
|
Posterior Blepharitis
No
|
6 Participants
n=5 Participants
|
|
Visually Significant Cataract
Yes
|
35 Participants
n=5 Participants
|
|
Visually Significant Cataract
No
|
40 Participants
n=5 Participants
|
|
Anterior Blepharitis
Yes
|
31 Participants
n=5 Participants
|
|
Anterior Blepharitis
No
|
44 Participants
n=5 Participants
|
|
Punctal plugs
Yes
|
27 Participants
n=5 Participants
|
|
Punctal plugs
No
|
48 Participants
n=5 Participants
|
|
Sjögren's
Yes
|
27 Participants
n=5 Participants
|
|
Sjögren's
No
|
48 Participants
n=5 Participants
|
|
Pseudophakia
Yes
|
15 Participants
n=5 Participants
|
|
Pseudophakia
No
|
60 Participants
n=5 Participants
|
|
Conjunctival Scarring/Punctal stenosis
Yes
|
6 Participants
n=5 Participants
|
|
Conjunctival Scarring/Punctal stenosis
No
|
69 Participants
n=5 Participants
|
|
Corneal Haze/Scarring
Yes
|
3 Participants
n=5 Participants
|
|
Corneal Haze/Scarring
No
|
72 Participants
n=5 Participants
|
|
Corneal Vascularization
Yes
|
1 Participants
n=5 Participants
|
|
Corneal Vascularization
No
|
74 Participants
n=5 Participants
|
|
History of Corneal Ulceration
Yes
|
2 Participants
n=5 Participants
|
|
History of Corneal Ulceration
No
|
73 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 28 daysPopulation: Only 75 (150 eyes) patients' data were analyzed as 2 patients were lost to follow-up before 28 days.
OSS will be graded according to the Sjögren's International Collaborative Clinical Alliance (SICCA) grading system. Maximum possible fluorescein score (the punctate epithelial erosions grade + any extra points for modifiers \[central staining, confluent staining, and filaments\]) will be 6 and minimum of 0. Maximum possible conjunctival staining score (the punctate epithelial erosions grade on the temporal and nasal sides) will be 6 and minimum of 0. The total possible maximum OSS, derived by summing the corneal and conjunctival scores, will be 12 for each eye, and minimum OSS will be 0. Higher corneal, conjunctival, and staining scores represent worse outcomes. The difference between the average corneal staining in the treated arm versus the average corneal staining in the sham arm will be compared statistically.
Outcome measures
| Measure |
Treatment Arm
n=75 eyes
Commercially available Sustained Release Dexamethasone, 0.4 mg intracannalicular insert (DEXTENZA® - Ocular Therapeutix, Bedford, MA)
Sustained Release Dexamethasone, 0.4 mg: dexamethasone 0.4mg lacrimal insert
|
Control Arm
n=75 eyes
FCIProlong® made of E-Caprolactone-L-Lactide copolymer (PCL) (FCI Ophthalmics Inc., Pembroke, MA)
E-Caprolactone-L-Lactide copolymer (PCL) punctal plug: Control eye will receive a tear duct plug without the dexamethasone (EXTENDED WEAR SYNTHETIC ABSORBABLE PUNCTAL PLUG made of E-Caprolactone-L-Lactide copolymer (PCL). Absorbs in 60 to 180 days. Size 0.5mm which is comparable to the study treatment)
|
|---|---|---|
|
Efficacy Endpoint as Assessed by Dry Eye Sign Using Ocular Surface Scale (OSS)
Day 28 Corneal Staining Mean Staining
|
2.15 score on a scale
Standard Deviation 1.31
|
2.70 score on a scale
Standard Deviation 1.33
|
|
Efficacy Endpoint as Assessed by Dry Eye Sign Using Ocular Surface Scale (OSS)
Day 28 Corneal Staining Mean Staining - Subgroup 18-59
|
2.14 score on a scale
Standard Deviation 1.29
|
2.64 score on a scale
Standard Deviation 1.55
|
|
Efficacy Endpoint as Assessed by Dry Eye Sign Using Ocular Surface Scale (OSS)
Day 28 Corneal Staining Mean Staining - Subgroup 60+
|
2.13 score on a scale
Standard Deviation 0.36
|
3.06 score on a scale
Standard Deviation 1.12
|
|
Efficacy Endpoint as Assessed by Dry Eye Sign Using Ocular Surface Scale (OSS)
Day 28 Corneal Staining Subgroup analysis by Sjögren's status - Yes
|
2.54 score on a scale
Standard Deviation 1.20
|
3.23 score on a scale
Standard Deviation 1.42
|
|
Efficacy Endpoint as Assessed by Dry Eye Sign Using Ocular Surface Scale (OSS)
Day 28 Corneal Staining Subgroup analysis by Sjögren's status - No
|
1.82 score on a scale
Standard Deviation 1.43
|
2.59 score on a scale
Standard Deviation 1.23
|
|
Efficacy Endpoint as Assessed by Dry Eye Sign Using Ocular Surface Scale (OSS)
Day 28 Conjunctival Staining Mean Staining
|
3.01 score on a scale
Standard Deviation 1.89
|
3.69 score on a scale
Standard Deviation 1.69
|
|
Efficacy Endpoint as Assessed by Dry Eye Sign Using Ocular Surface Scale (OSS)
Day 28 Conjunctival Staining Mean Staining - Subgroup 18-59
|
3.50 score on a scale
Standard Deviation 2.35
|
2.69 score on a scale
Standard Deviation 1.89
|
|
Efficacy Endpoint as Assessed by Dry Eye Sign Using Ocular Surface Scale (OSS)
Day 28 Conjunctival Staining Mean Staining - Subgroup 60+
|
2.69 score on a scale
Standard Deviation 1.89
|
3.88 score on a scale
Standard Deviation 1.41
|
|
Efficacy Endpoint as Assessed by Dry Eye Sign Using Ocular Surface Scale (OSS)
Day 28 Conjunctival Staining Subgroup analysis by Sjögren's status - Yes
|
3.31 score on a scale
Standard Deviation 2.39
|
4.09 score on a scale
Standard Deviation 1.55
|
|
Efficacy Endpoint as Assessed by Dry Eye Sign Using Ocular Surface Scale (OSS)
Day 28 Conjunctival Staining Subgroup analysis by Sjögren's status - No
|
2.88 score on a scale
Standard Deviation 1.93
|
3.59 score on a scale
Standard Deviation 1.41
|
PRIMARY outcome
Timeframe: 28 DaysPopulation: Only 75 (150 eyes) patients' data were analyzed as 2 patients were lost to follow-up before 28 days.
(1)eye dryness, (2)eye discomfort, or (3)eye fatigue will be measured using visual analogue scale (0 to 100). The difference between the average bothersome symptom in the treated arm versus the average most bothersome symptom in the sham arm will be compared statistically. Higher VAS scores indicate worse eye dryness, discomfort, or fatigue.
Outcome measures
| Measure |
Treatment Arm
n=75 eyes
Commercially available Sustained Release Dexamethasone, 0.4 mg intracannalicular insert (DEXTENZA® - Ocular Therapeutix, Bedford, MA)
Sustained Release Dexamethasone, 0.4 mg: dexamethasone 0.4mg lacrimal insert
|
Control Arm
n=75 eyes
FCIProlong® made of E-Caprolactone-L-Lactide copolymer (PCL) (FCI Ophthalmics Inc., Pembroke, MA)
E-Caprolactone-L-Lactide copolymer (PCL) punctal plug: Control eye will receive a tear duct plug without the dexamethasone (EXTENDED WEAR SYNTHETIC ABSORBABLE PUNCTAL PLUG made of E-Caprolactone-L-Lactide copolymer (PCL). Absorbs in 60 to 180 days. Size 0.5mm which is comparable to the study treatment)
|
|---|---|---|
|
Patient Reported Symptom
Day 28 Eye Dryness VAS Mean Score
|
49.3 units on a scale
Standard Deviation 26.4
|
54.8 units on a scale
Standard Deviation 23.0
|
|
Patient Reported Symptom
Day 28 Eye Discomfort VAS Mean Score
|
50.3 units on a scale
Standard Deviation 27.7
|
50.6 units on a scale
Standard Deviation 26.0
|
|
Patient Reported Symptom
Day 28 Eye Fatigue VAS Mean Score
|
43.7 units on a scale
Standard Deviation 27.5
|
45.0 units on a scale
Standard Deviation 26.7
|
SECONDARY outcome
Timeframe: 42 daysPopulation: 74 (148 eyes) patients' data were analyzed as 3 patients were lost to follow-up before 42 days.
Corneal staining responder analysis. Responder is defined as two full severity grade improvement in corneal staining. The percentage of subjects achieving two severity grades improvement in corneal staining (responders) in the treated arm versus sham arm will be compared statistically.
Outcome measures
| Measure |
Treatment Arm
n=74 eyes
Commercially available Sustained Release Dexamethasone, 0.4 mg intracannalicular insert (DEXTENZA® - Ocular Therapeutix, Bedford, MA)
Sustained Release Dexamethasone, 0.4 mg: dexamethasone 0.4mg lacrimal insert
|
Control Arm
n=74 eyes
FCIProlong® made of E-Caprolactone-L-Lactide copolymer (PCL) (FCI Ophthalmics Inc., Pembroke, MA)
E-Caprolactone-L-Lactide copolymer (PCL) punctal plug: Control eye will receive a tear duct plug without the dexamethasone (EXTENDED WEAR SYNTHETIC ABSORBABLE PUNCTAL PLUG made of E-Caprolactone-L-Lactide copolymer (PCL). Absorbs in 60 to 180 days. Size 0.5mm which is comparable to the study treatment)
|
|---|---|---|
|
Percentage of Subjects Achieving 2 Severity Grade Improvement in Corneal Staining
|
32 Percentage of responders
|
26 Percentage of responders
|
SECONDARY outcome
Timeframe: 42 daysPopulation: 74 (148 eyes) patients' data were analyzed as 3 patients were lost to follow-up before 42 days.
Symptom responder analysis. Responder is defined as 30% or more improvement in the most bothersome symptom (VAS score is decreased by 30 points or more). The percentage of subjects achieving a 30% improvement in their most bothersome symptom (responders) in the treated arm versus the sham arm will be compared statistically.
Outcome measures
| Measure |
Treatment Arm
n=74 eyes
Commercially available Sustained Release Dexamethasone, 0.4 mg intracannalicular insert (DEXTENZA® - Ocular Therapeutix, Bedford, MA)
Sustained Release Dexamethasone, 0.4 mg: dexamethasone 0.4mg lacrimal insert
|
Control Arm
n=74 eyes
FCIProlong® made of E-Caprolactone-L-Lactide copolymer (PCL) (FCI Ophthalmics Inc., Pembroke, MA)
E-Caprolactone-L-Lactide copolymer (PCL) punctal plug: Control eye will receive a tear duct plug without the dexamethasone (EXTENDED WEAR SYNTHETIC ABSORBABLE PUNCTAL PLUG made of E-Caprolactone-L-Lactide copolymer (PCL). Absorbs in 60 to 180 days. Size 0.5mm which is comparable to the study treatment)
|
|---|---|---|
|
Percentage of Subjects Achieving Improvement in Their Most Bothersome Symptom
|
38 Percentage of responders
|
37 Percentage of responders
|
OTHER_PRE_SPECIFIED outcome
Timeframe: At day 30 and day 42Population: 75 (150 eyes) patients' data were analyzed at day 30. 74 (148 eyes) patients' data were analyzed at day 42.
Intraocular Pressure (IOP) measurement obtained using applanation tonometry
Outcome measures
| Measure |
Treatment Arm
n=75 eyes
Commercially available Sustained Release Dexamethasone, 0.4 mg intracannalicular insert (DEXTENZA® - Ocular Therapeutix, Bedford, MA)
Sustained Release Dexamethasone, 0.4 mg: dexamethasone 0.4mg lacrimal insert
|
Control Arm
n=75 eyes
FCIProlong® made of E-Caprolactone-L-Lactide copolymer (PCL) (FCI Ophthalmics Inc., Pembroke, MA)
E-Caprolactone-L-Lactide copolymer (PCL) punctal plug: Control eye will receive a tear duct plug without the dexamethasone (EXTENDED WEAR SYNTHETIC ABSORBABLE PUNCTAL PLUG made of E-Caprolactone-L-Lactide copolymer (PCL). Absorbs in 60 to 180 days. Size 0.5mm which is comparable to the study treatment)
|
|---|---|---|
|
Percentage of Participants With Intraocular Pressure Increase
Day 30 : Raised intraocular pressure (increase by 5-10 mm Hg from baseline)
|
12 percentage of subjects with IOP increase
|
1 percentage of subjects with IOP increase
|
|
Percentage of Participants With Intraocular Pressure Increase
Day 30 : Raised intraocular pressure (increase by >10 mm Hg from baseline)
|
0 percentage of subjects with IOP increase
|
0 percentage of subjects with IOP increase
|
|
Percentage of Participants With Intraocular Pressure Increase
Day 42 : Raised intraocular pressure (increase by 5-10 mm Hg from baseline)
|
11 percentage of subjects with IOP increase
|
4 percentage of subjects with IOP increase
|
|
Percentage of Participants With Intraocular Pressure Increase
Day 42 : Raised intraocular pressure (increase by >10 mm Hg from baseline)
|
3 percentage of subjects with IOP increase
|
1 percentage of subjects with IOP increase
|
Adverse Events
Treatment Arm
Serious events: 1 serious events
Other events: 19 other events
Deaths: 0 deaths
Control Arm
Serious events: 1 serious events
Other events: 10 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Treatment Arm
n=77 participants at risk
Treatment:
Commercially available Sustained Release Dexamethasone, 0.4 mg intracannalicular insert (DEXTENZA® - Ocular Therapeutix, Bedford, MA) Sustained Release Dexamethasone, 0.4 mg: dexamethasone 0.4mg lacrimal insert
|
Control Arm
n=77 participants at risk
Control:
FCIProlong® made of E-Caprolactone-L-Lactide copolymer (PCL) (FCI Ophthalmics Inc., Pembroke, MA) E-Caprolactone-L-Lactide copolymer (PCL) punctal plug: Control eye will receive a tear duct plug without the dexamethasone (EXTENDED WEAR SYNTHETIC ABSORBABLE PUNCTAL PLUG made of E-Caprolactone-L-Lactide copolymer (PCL). Absorbs in 60 to 180 days. Size 0.5mm which is comparable to the study treatment)
|
|---|---|---|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Day 14
|
1.3%
1/77 • Number of events 1 • Up to 42 days
|
1.3%
1/77 • Number of events 77 • Up to 42 days
|
Other adverse events
| Measure |
Treatment Arm
n=77 participants at risk
Treatment:
Commercially available Sustained Release Dexamethasone, 0.4 mg intracannalicular insert (DEXTENZA® - Ocular Therapeutix, Bedford, MA) Sustained Release Dexamethasone, 0.4 mg: dexamethasone 0.4mg lacrimal insert
|
Control Arm
n=77 participants at risk
Control:
FCIProlong® made of E-Caprolactone-L-Lactide copolymer (PCL) (FCI Ophthalmics Inc., Pembroke, MA) E-Caprolactone-L-Lactide copolymer (PCL) punctal plug: Control eye will receive a tear duct plug without the dexamethasone (EXTENDED WEAR SYNTHETIC ABSORBABLE PUNCTAL PLUG made of E-Caprolactone-L-Lactide copolymer (PCL). Absorbs in 60 to 180 days. Size 0.5mm which is comparable to the study treatment)
|
|---|---|---|
|
Eye disorders
Week 6: Raised intraocular pressure (increase by 5-10 mm Hg from baseline)
|
10.4%
8/77 • Number of events 8 • Up to 42 days
|
3.9%
3/77 • Number of events 3 • Up to 42 days
|
|
Eye disorders
Week 6: Raised intraocular pressure (increase by >10 mm Hg from baseline)
|
2.6%
2/77 • Number of events 2 • Up to 42 days
|
1.3%
1/77 • Number of events 1 • Up to 42 days
|
|
Eye disorders
Week 6: Worsening of Corneal Fluorescein staining (increase by ≥2 from baseline)
|
2.6%
2/77 • Number of events 2 • Up to 42 days
|
2.6%
2/77 • Number of events 2 • Up to 42 days
|
|
Eye disorders
Week 6: Worsening of conjunctival lissamine green staining (increase by ≥2 from baseline)
|
9.1%
7/77 • Number of events 7 • Up to 42 days
|
5.2%
4/77 • Number of events 4 • Up to 42 days
|
Additional Information
Michael Lin, BA, Research coordinator
Johns Hopkins Wilmer Eye Institute
Phone: 8653851192
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place