Trial Outcomes & Findings for Study to Evaluate ISV-305 Compared to Vehicle for Treatment of Inflammation and Pain Associated With Cataract Surgery (NCT NCT03192137)

NCT ID: NCT03192137

Last Updated: 2021-11-19

Results Overview

Biomicroscopic measurement of anterior chamber cells was conducted in the surgery eye (study eye) by the same examiner from visit to visit whenever possible. A slit-lamp biomicroscope was used at x16 magnification with a 1 x 1 mm oblique high-intensity beam. Two cell counts were summed and divided by 2 to determine an average final anterior chamber cell count. This final cell count was converted to a grade: Grades 0, 1, 2, 3, 4 were assigned for cell counts of 0, 1 to 10, 11 to 20, 21 to 50, and \> 50, respectively. If the averaged count fell between two grades, the higher grade was selected (e.g., if the two counts were 10 and 11, the average of 10.5 fell into Grade 2). Missing anterior chamber cell grade at Day 15 was imputed by last non-missing scheduled post-baseline anterior chamber cell grade assessed prior to Day 15 (last observation carried forward).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

260 participants

Primary outcome timeframe

Day 15

Results posted on

2021-11-19

Participant Flow

Participant milestones

Participant milestones
Measure	ISV-305 ISV-305 was administered as a topical ophthalmic formulation of 0.1% dexamethasone in DuraSite® 2 vehicle (InSite Vision's drug delivery system) twice daily (one drop in the morning and one drop in the evening) for 16 days.	Vehicle Vehicle (DuraSite® 2 vehicle) was administered as a matching topical ophthalmic formulation without dexamethasone twice daily (one drop in the morning and one drop in the evening) for 16 days.
Overall Study STARTED	173	87
Overall Study COMPLETED	123	29
Overall Study NOT COMPLETED	50	58

Reasons for withdrawal

Reasons for withdrawal
Measure	ISV-305 ISV-305 was administered as a topical ophthalmic formulation of 0.1% dexamethasone in DuraSite® 2 vehicle (InSite Vision's drug delivery system) twice daily (one drop in the morning and one drop in the evening) for 16 days.	Vehicle Vehicle (DuraSite® 2 vehicle) was administered as a matching topical ophthalmic formulation without dexamethasone twice daily (one drop in the morning and one drop in the evening) for 16 days.
Overall Study Adverse Event	10	11
Overall Study Physician Decision	1	0
Overall Study Lack of Efficacy	20	37
Overall Study Withdrawal by Subject	3	3
Overall Study Protocol Violation	4	3
Overall Study Surgery Cancelled	4	1
Overall Study Other - Various Administrative Reasons	8	3

Baseline Characteristics

Study to Evaluate ISV-305 Compared to Vehicle for Treatment of Inflammation and Pain Associated With Cataract Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ISV-305 n=158 Participants ISV-305 was administered as a topical ophthalmic formulation of 0.1% dexamethasone in DuraSite® 2 vehicle (InSite Vision's drug delivery system) twice daily (one drop in the morning and one drop in the evening) for 16 days.	Vehicle n=80 Participants Vehicle (DuraSite® 2 vehicle) was administered as a matching topical ophthalmic formulation without dexamethasone twice daily (one drop in the morning and one drop in the evening) for 16 days.	Total n=238 Participants Total of all reporting groups
Age, Continuous	68.0 Years STANDARD_DEVIATION 7.15 • n=99 Participants	68.5 Years STANDARD_DEVIATION 9.37 • n=107 Participants	68.2 Years STANDARD_DEVIATION 7.95 • n=206 Participants
Sex: Female, Male Female	94 Participants n=99 Participants	43 Participants n=107 Participants	137 Participants n=206 Participants
Sex: Female, Male Male	64 Participants n=99 Participants	37 Participants n=107 Participants	101 Participants n=206 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants
Race/Ethnicity, Customized Asian	4 Participants n=99 Participants	2 Participants n=107 Participants	6 Participants n=206 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race/Ethnicity, Customized Black or African American	10 Participants n=99 Participants	5 Participants n=107 Participants	15 Participants n=206 Participants
Race/Ethnicity, Customized White	141 Participants n=99 Participants	72 Participants n=107 Participants	213 Participants n=206 Participants
Race/Ethnicity, Customized Mixed	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants
Race/Ethnicity, Customized Other	2 Participants n=99 Participants	0 Participants n=107 Participants	2 Participants n=206 Participants

PRIMARY outcome

Timeframe: Day 15

Population: mITT Population - included randomized participants who underwent cataract surgery, received at least one dose of ISV-305 or vehicle, and had at least one post-surgery efficacy assessment (ACC or VAS). Participants who received rescue medications were included in the mITT Population, but were treated as failures.

Outcome measures

Outcome measures
Measure	ISV-305 n=144 Participants ISV-305 was administered as a topical ophthalmic formulation of 0.1% dexamethasone in DuraSite® 2 vehicle (InSite Vision's drug delivery system) twice daily (one drop in the morning and one drop in the evening) for 16 days.	Vehicle n=72 Participants Vehicle (DuraSite® 2 vehicle) was administered as a matching topical ophthalmic formulation without dexamethasone twice daily (one drop in the morning and one drop in the evening) for 16 days.
Proportion of Participants With Anterior Chamber Cell (ACC) Grade 0 in Study Eye at Day 15 (Last Observation Carried Forward) in the Modified Intent to Treat (mITT) Population 0 (did not receive rescue therapy)	69 participants	16 participants
Proportion of Participants With Anterior Chamber Cell (ACC) Grade 0 in Study Eye at Day 15 (Last Observation Carried Forward) in the Modified Intent to Treat (mITT) Population 0 (received rescue therapy)	0 participants	0 participants
Proportion of Participants With Anterior Chamber Cell (ACC) Grade 0 in Study Eye at Day 15 (Last Observation Carried Forward) in the Modified Intent to Treat (mITT) Population 1	64 participants	30 participants
Proportion of Participants With Anterior Chamber Cell (ACC) Grade 0 in Study Eye at Day 15 (Last Observation Carried Forward) in the Modified Intent to Treat (mITT) Population 2	5 participants	10 participants
Proportion of Participants With Anterior Chamber Cell (ACC) Grade 0 in Study Eye at Day 15 (Last Observation Carried Forward) in the Modified Intent to Treat (mITT) Population 3	6 participants	12 participants
Proportion of Participants With Anterior Chamber Cell (ACC) Grade 0 in Study Eye at Day 15 (Last Observation Carried Forward) in the Modified Intent to Treat (mITT) Population 4	0 participants	4 participants

SECONDARY outcome

Timeframe: Day 1 to Day 29

Eye pain/discomfort in the study eye was evaluated at every visit except Visit 2 (Surgery; Day 0) using a VAS, scoring from 0 to 100 using a mark on a 100 mm line (0 = absent; 100 = maximum). Participants were asked to rate the feeling of the symptom in the study eye from absent to extreme by moving a slide on the side of the scale to align with images of descriptive faces.

Outcome measures

Outcome measures
Measure	ISV-305 n=156 Participants ISV-305 was administered as a topical ophthalmic formulation of 0.1% dexamethasone in DuraSite® 2 vehicle (InSite Vision's drug delivery system) twice daily (one drop in the morning and one drop in the evening) for 16 days.	Vehicle n=77 Participants Vehicle (DuraSite® 2 vehicle) was administered as a matching topical ophthalmic formulation without dexamethasone twice daily (one drop in the morning and one drop in the evening) for 16 days.
Proportion of Participants Who Achieved a Pain Score of 0 on the Visual Analog Scale (VAS) for Each Post-surgical Assessment Pain Score of 0 on Day 1	103 Participants	29 Participants
Proportion of Participants Who Achieved a Pain Score of 0 on the Visual Analog Scale (VAS) for Each Post-surgical Assessment Pain Score of 0 on Day 8	133 Participants	44 Participants
Proportion of Participants Who Achieved a Pain Score of 0 on the Visual Analog Scale (VAS) for Each Post-surgical Assessment Pain Score of 0 on Day 15	137 Participants	49 Participants
Proportion of Participants Who Achieved a Pain Score of 0 on the Visual Analog Scale (VAS) for Each Post-surgical Assessment Pain Score of 0 on Day 18	129 Participants	50 Participants
Proportion of Participants Who Achieved a Pain Score of 0 on the Visual Analog Scale (VAS) for Each Post-surgical Assessment Pain Score of 0 on Day 29	135 Participants	51 Participants

Adverse Events

ISV-305

Serious events: 3 serious events

Other events: 31 other events

Deaths: 0 deaths

Vehicle

Serious events: 0 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	ISV-305 n=158 participants at risk ISV-305 was administered as a topical ophthalmic formulation of 0.1% dexamethasone in DuraSite® 2 vehicle (InSite Vision's drug delivery system) twice daily (one drop in the morning and one drop in the evening) for 16 days.	Vehicle n=80 participants at risk Vehicle (DuraSite® 2 vehicle) was administered as a matching topical ophthalmic formulation without dexamethasone twice daily (one drop in the morning and one drop in the evening) for 16 days.
General disorders Chest pain	0.63% 1/158 • Adverse events (AEs) were reported from the date of signing the consent form to the date of completion of the participant's final visit (Day 29). Ongoing AEs were followed beyond the final study visit at the discretion of the investigator. Treatment-emergent adverse events were summarized for the Safety Population, which included all randomized participants who received at least one dose of study treatment (i.e., 158 and 80 subjects in the ISV-305 and Vehicle arms, respectively).	0.00% 0/80 • Adverse events (AEs) were reported from the date of signing the consent form to the date of completion of the participant's final visit (Day 29). Ongoing AEs were followed beyond the final study visit at the discretion of the investigator. Treatment-emergent adverse events were summarized for the Safety Population, which included all randomized participants who received at least one dose of study treatment (i.e., 158 and 80 subjects in the ISV-305 and Vehicle arms, respectively).
Cardiac disorders Atrial flutter	0.63% 1/158 • Adverse events (AEs) were reported from the date of signing the consent form to the date of completion of the participant's final visit (Day 29). Ongoing AEs were followed beyond the final study visit at the discretion of the investigator. Treatment-emergent adverse events were summarized for the Safety Population, which included all randomized participants who received at least one dose of study treatment (i.e., 158 and 80 subjects in the ISV-305 and Vehicle arms, respectively).	0.00% 0/80 • Adverse events (AEs) were reported from the date of signing the consent form to the date of completion of the participant's final visit (Day 29). Ongoing AEs were followed beyond the final study visit at the discretion of the investigator. Treatment-emergent adverse events were summarized for the Safety Population, which included all randomized participants who received at least one dose of study treatment (i.e., 158 and 80 subjects in the ISV-305 and Vehicle arms, respectively).
Investigations Blood magnesium decreased	0.63% 1/158 • Adverse events (AEs) were reported from the date of signing the consent form to the date of completion of the participant's final visit (Day 29). Ongoing AEs were followed beyond the final study visit at the discretion of the investigator. Treatment-emergent adverse events were summarized for the Safety Population, which included all randomized participants who received at least one dose of study treatment (i.e., 158 and 80 subjects in the ISV-305 and Vehicle arms, respectively).	0.00% 0/80 • Adverse events (AEs) were reported from the date of signing the consent form to the date of completion of the participant's final visit (Day 29). Ongoing AEs were followed beyond the final study visit at the discretion of the investigator. Treatment-emergent adverse events were summarized for the Safety Population, which included all randomized participants who received at least one dose of study treatment (i.e., 158 and 80 subjects in the ISV-305 and Vehicle arms, respectively).
Gastrointestinal disorders Vomiting	0.63% 1/158 • Adverse events (AEs) were reported from the date of signing the consent form to the date of completion of the participant's final visit (Day 29). Ongoing AEs were followed beyond the final study visit at the discretion of the investigator. Treatment-emergent adverse events were summarized for the Safety Population, which included all randomized participants who received at least one dose of study treatment (i.e., 158 and 80 subjects in the ISV-305 and Vehicle arms, respectively).	0.00% 0/80 • Adverse events (AEs) were reported from the date of signing the consent form to the date of completion of the participant's final visit (Day 29). Ongoing AEs were followed beyond the final study visit at the discretion of the investigator. Treatment-emergent adverse events were summarized for the Safety Population, which included all randomized participants who received at least one dose of study treatment (i.e., 158 and 80 subjects in the ISV-305 and Vehicle arms, respectively).
Respiratory, thoracic and mediastinal disorders Pulmonary thrombosis	0.63% 1/158 • Adverse events (AEs) were reported from the date of signing the consent form to the date of completion of the participant's final visit (Day 29). Ongoing AEs were followed beyond the final study visit at the discretion of the investigator. Treatment-emergent adverse events were summarized for the Safety Population, which included all randomized participants who received at least one dose of study treatment (i.e., 158 and 80 subjects in the ISV-305 and Vehicle arms, respectively).	0.00% 0/80 • Adverse events (AEs) were reported from the date of signing the consent form to the date of completion of the participant's final visit (Day 29). Ongoing AEs were followed beyond the final study visit at the discretion of the investigator. Treatment-emergent adverse events were summarized for the Safety Population, which included all randomized participants who received at least one dose of study treatment (i.e., 158 and 80 subjects in the ISV-305 and Vehicle arms, respectively).

Other adverse events

Other adverse events
Measure	ISV-305 n=158 participants at risk ISV-305 was administered as a topical ophthalmic formulation of 0.1% dexamethasone in DuraSite® 2 vehicle (InSite Vision's drug delivery system) twice daily (one drop in the morning and one drop in the evening) for 16 days.	Vehicle n=80 participants at risk Vehicle (DuraSite® 2 vehicle) was administered as a matching topical ophthalmic formulation without dexamethasone twice daily (one drop in the morning and one drop in the evening) for 16 days.
Eye disorders Iritis	3.8% 6/158 • Adverse events (AEs) were reported from the date of signing the consent form to the date of completion of the participant's final visit (Day 29). Ongoing AEs were followed beyond the final study visit at the discretion of the investigator. Treatment-emergent adverse events were summarized for the Safety Population, which included all randomized participants who received at least one dose of study treatment (i.e., 158 and 80 subjects in the ISV-305 and Vehicle arms, respectively).	6.2% 5/80 • Adverse events (AEs) were reported from the date of signing the consent form to the date of completion of the participant's final visit (Day 29). Ongoing AEs were followed beyond the final study visit at the discretion of the investigator. Treatment-emergent adverse events were summarized for the Safety Population, which included all randomized participants who received at least one dose of study treatment (i.e., 158 and 80 subjects in the ISV-305 and Vehicle arms, respectively).
Eye disorders Visual acuity reduced	4.4% 7/158 • Adverse events (AEs) were reported from the date of signing the consent form to the date of completion of the participant's final visit (Day 29). Ongoing AEs were followed beyond the final study visit at the discretion of the investigator. Treatment-emergent adverse events were summarized for the Safety Population, which included all randomized participants who received at least one dose of study treatment (i.e., 158 and 80 subjects in the ISV-305 and Vehicle arms, respectively).	2.5% 2/80 • Adverse events (AEs) were reported from the date of signing the consent form to the date of completion of the participant's final visit (Day 29). Ongoing AEs were followed beyond the final study visit at the discretion of the investigator. Treatment-emergent adverse events were summarized for the Safety Population, which included all randomized participants who received at least one dose of study treatment (i.e., 158 and 80 subjects in the ISV-305 and Vehicle arms, respectively).
Eye disorders Eye pain	1.9% 3/158 • Adverse events (AEs) were reported from the date of signing the consent form to the date of completion of the participant's final visit (Day 29). Ongoing AEs were followed beyond the final study visit at the discretion of the investigator. Treatment-emergent adverse events were summarized for the Safety Population, which included all randomized participants who received at least one dose of study treatment (i.e., 158 and 80 subjects in the ISV-305 and Vehicle arms, respectively).	5.0% 4/80 • Adverse events (AEs) were reported from the date of signing the consent form to the date of completion of the participant's final visit (Day 29). Ongoing AEs were followed beyond the final study visit at the discretion of the investigator. Treatment-emergent adverse events were summarized for the Safety Population, which included all randomized participants who received at least one dose of study treatment (i.e., 158 and 80 subjects in the ISV-305 and Vehicle arms, respectively).
Eye disorders Cystoid macular oedema	1.3% 2/158 • Adverse events (AEs) were reported from the date of signing the consent form to the date of completion of the participant's final visit (Day 29). Ongoing AEs were followed beyond the final study visit at the discretion of the investigator. Treatment-emergent adverse events were summarized for the Safety Population, which included all randomized participants who received at least one dose of study treatment (i.e., 158 and 80 subjects in the ISV-305 and Vehicle arms, respectively).	3.8% 3/80 • Adverse events (AEs) were reported from the date of signing the consent form to the date of completion of the participant's final visit (Day 29). Ongoing AEs were followed beyond the final study visit at the discretion of the investigator. Treatment-emergent adverse events were summarized for the Safety Population, which included all randomized participants who received at least one dose of study treatment (i.e., 158 and 80 subjects in the ISV-305 and Vehicle arms, respectively).
Eye disorders Eye inflammation	0.63% 1/158 • Adverse events (AEs) were reported from the date of signing the consent form to the date of completion of the participant's final visit (Day 29). Ongoing AEs were followed beyond the final study visit at the discretion of the investigator. Treatment-emergent adverse events were summarized for the Safety Population, which included all randomized participants who received at least one dose of study treatment (i.e., 158 and 80 subjects in the ISV-305 and Vehicle arms, respectively).	5.0% 4/80 • Adverse events (AEs) were reported from the date of signing the consent form to the date of completion of the participant's final visit (Day 29). Ongoing AEs were followed beyond the final study visit at the discretion of the investigator. Treatment-emergent adverse events were summarized for the Safety Population, which included all randomized participants who received at least one dose of study treatment (i.e., 158 and 80 subjects in the ISV-305 and Vehicle arms, respectively).
Eye disorders Foreign body sensation in eyes	1.3% 2/158 • Adverse events (AEs) were reported from the date of signing the consent form to the date of completion of the participant's final visit (Day 29). Ongoing AEs were followed beyond the final study visit at the discretion of the investigator. Treatment-emergent adverse events were summarized for the Safety Population, which included all randomized participants who received at least one dose of study treatment (i.e., 158 and 80 subjects in the ISV-305 and Vehicle arms, respectively).	3.8% 3/80 • Adverse events (AEs) were reported from the date of signing the consent form to the date of completion of the participant's final visit (Day 29). Ongoing AEs were followed beyond the final study visit at the discretion of the investigator. Treatment-emergent adverse events were summarized for the Safety Population, which included all randomized participants who received at least one dose of study treatment (i.e., 158 and 80 subjects in the ISV-305 and Vehicle arms, respectively).
Eye disorders Visual impairment	2.5% 4/158 • Adverse events (AEs) were reported from the date of signing the consent form to the date of completion of the participant's final visit (Day 29). Ongoing AEs were followed beyond the final study visit at the discretion of the investigator. Treatment-emergent adverse events were summarized for the Safety Population, which included all randomized participants who received at least one dose of study treatment (i.e., 158 and 80 subjects in the ISV-305 and Vehicle arms, respectively).	1.2% 1/80 • Adverse events (AEs) were reported from the date of signing the consent form to the date of completion of the participant's final visit (Day 29). Ongoing AEs were followed beyond the final study visit at the discretion of the investigator. Treatment-emergent adverse events were summarized for the Safety Population, which included all randomized participants who received at least one dose of study treatment (i.e., 158 and 80 subjects in the ISV-305 and Vehicle arms, respectively).
Investigations Intraocular pressure increased	6.3% 10/158 • Adverse events (AEs) were reported from the date of signing the consent form to the date of completion of the participant's final visit (Day 29). Ongoing AEs were followed beyond the final study visit at the discretion of the investigator. Treatment-emergent adverse events were summarized for the Safety Population, which included all randomized participants who received at least one dose of study treatment (i.e., 158 and 80 subjects in the ISV-305 and Vehicle arms, respectively).	2.5% 2/80 • Adverse events (AEs) were reported from the date of signing the consent form to the date of completion of the participant's final visit (Day 29). Ongoing AEs were followed beyond the final study visit at the discretion of the investigator. Treatment-emergent adverse events were summarized for the Safety Population, which included all randomized participants who received at least one dose of study treatment (i.e., 158 and 80 subjects in the ISV-305 and Vehicle arms, respectively).
Nervous system disorders Headache	0.63% 1/158 • Adverse events (AEs) were reported from the date of signing the consent form to the date of completion of the participant's final visit (Day 29). Ongoing AEs were followed beyond the final study visit at the discretion of the investigator. Treatment-emergent adverse events were summarized for the Safety Population, which included all randomized participants who received at least one dose of study treatment (i.e., 158 and 80 subjects in the ISV-305 and Vehicle arms, respectively).	2.5% 2/80 • Adverse events (AEs) were reported from the date of signing the consent form to the date of completion of the participant's final visit (Day 29). Ongoing AEs were followed beyond the final study visit at the discretion of the investigator. Treatment-emergent adverse events were summarized for the Safety Population, which included all randomized participants who received at least one dose of study treatment (i.e., 158 and 80 subjects in the ISV-305 and Vehicle arms, respectively).

Additional Information

Senior Manager, Clinical Sciences

InSite Vision

Phone: +91 9987096080

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The investigator agrees to submit the manuscript of any journal article, abstract or other presentation arising from an InSite Vision-sponsored clinical investigation to InSite Vision for editorial review prior to submission for publication or presentation. At the sponsor's request, if proprietary information is to be disclosed, proposed publications or presentations will be delayed until appropriate patent applications and/or legal documents of a similar nature have been filed.
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