Trial Outcomes & Findings for Comparative Study to Evaluate ISV-305 Compared to Vehicle in Blepharitis Subjects (NCT NCT01543490)

Last Updated: 2021-11-19

Results Overview

The clinical signs of blepharitis (eyelid swelling, eyelid redness, eyelid debris) were evaluated at every visit and scored by the investigator using a 0 to 3 grading scale (in general 0 = none, 1 = mild, 2 = moderate, and 3 = severe). The symptom of eyelid irritation was also evaluated at every visit and graded by the participant using a 0 to 3 grading scale (0 = almost none of the time - ≤ 25% of the time, 1 = occasionally - 26-50% of the time, 2 = frequently - 51-75% of the time, 3 = almost all of the time - ≥ 76% of the time). For each visit, the total clinical signs and symptom score was obtained by adding each of the individual scores for each domain (eyelid swelling, eyelid redness, eyelid debris, and eyelid irritation). Participants with a decrease in total clinical signs and symptom score at Day 15 by at least 2 units from Day 1 (baseline) with no increase in any sign and symptom were defined as Responders, and those not meeting these criteria were defined as Non-responders.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

558 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 14 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 14 days.
Overall Study STARTED	368	190
Overall Study COMPLETED	352	185
Overall Study NOT COMPLETED	16	5

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 14 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 14 days.
Overall Study Adverse Event	4	0
Overall Study Physician Decision	1	0
Overall Study Lack of Efficacy	3	3
Overall Study Lost to Follow-up	5	0
Overall Study Withdrawal by Subject	2	0
Overall Study Other-Various Administrative Reasons	1	2

Baseline Characteristics

Comparative Study to Evaluate ISV-305 Compared to Vehicle in Blepharitis Subjects

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ISV-305 n=368 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 14 days.	Vehicle n=190 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 14 days.	Total n=558 Participants Total of all reporting groups
Age, Customized < 17 years	0 Participants n=113 Participants	0 Participants n=163 Participants	0 Participants n=160 Participants
Age, Customized 17 to < 65 years	146 Participants n=113 Participants	66 Participants n=163 Participants	212 Participants n=160 Participants
Age, Customized ≥ 65 years	222 Participants n=113 Participants	124 Participants n=163 Participants	346 Participants n=160 Participants
Sex: Female, Male Female	209 Participants n=113 Participants	107 Participants n=163 Participants	316 Participants n=160 Participants
Sex: Female, Male Male	159 Participants n=113 Participants	83 Participants n=163 Participants	242 Participants n=160 Participants
Race/Ethnicity, Customized African American or Black	20 Participants n=113 Participants	2 Participants n=163 Participants	22 Participants n=160 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=113 Participants	0 Participants n=163 Participants	0 Participants n=160 Participants
Race/Ethnicity, Customized Asian	6 Participants n=113 Participants	3 Participants n=163 Participants	9 Participants n=160 Participants
Race/Ethnicity, Customized White	334 Participants n=113 Participants	184 Participants n=163 Participants	518 Participants n=160 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	2 Participants n=113 Participants	0 Participants n=163 Participants	2 Participants n=160 Participants
Race/Ethnicity, Customized Mixed	1 Participants n=113 Participants	0 Participants n=163 Participants	1 Participants n=160 Participants
Race/Ethnicity, Customized Other	5 Participants n=113 Participants	1 Participants n=163 Participants	6 Participants n=160 Participants
Region of Enrollment United States	368 Participants n=113 Participants	190 Participants n=163 Participants	558 Participants n=160 Participants

PRIMARY outcome

Timeframe: Day 15

Population: ITT Population, which included all randomized participants regardless of whether post-baseline measures were collected or study treatment was received. The participants only with valid measurement at Day 15 were used as the denominator for percentages (353 out of 368 participants for ISV-305 and 185 out of 190 participants in Vehicle).

Outcome measures

Outcome measures
Measure	ISV-305 n=353 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 14 days.	Vehicle n=185 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 14 days.
Number of Participants in the ITT Population With a Reduction in the Day 1 (Baseline) Total Clinical Signs and Symptom Score by at Least 2 Units at Day 15 With No Worsening of Any Sign or Symptom Responders	276 Participants	129 Participants
Number of Participants in the ITT Population With a Reduction in the Day 1 (Baseline) Total Clinical Signs and Symptom Score by at Least 2 Units at Day 15 With No Worsening of Any Sign or Symptom Non-responders	77 Participants	56 Participants

SECONDARY outcome

Timeframe: Day 15

Population: ITT Population, which included all randomized participants regardless of whether post-baseline measures were collected or study treatment was received. Participants with a valid post-baseline measurement on or before at Day 15 were used as the denominator for percentages (368 for ISV-305 and 190 for Vehicle).

Complete resolution of eyelid irritation, which was defined as eyelid irritation with grading of 0, at Day 15 was analyzed. The symptoms of eyelid irritation were graded by the participant using a 0 to 3 grading scale, where 0 = almost none of the time - ≤ 25% of the time, 1 = occasionally - 26-50% of the time, 2 = frequently - 51-75% of the time, 3 = almost all of the time - ≥ 76% of the time.

Outcome measures

Outcome measures
Measure	ISV-305 n=368 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 14 days.	Vehicle n=190 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 14 days.
Number of Participants With Complete Resolution of Eyelid Irritation (Last Observation Carried Forward [LOCF]) on Day 15 in ITT Population With Complete Resolution	127 Participants	52 Participants
Number of Participants With Complete Resolution of Eyelid Irritation (Last Observation Carried Forward [LOCF]) on Day 15 in ITT Population Without Complete Resolution	241 Participants	138 Participants

Adverse Events

ISV-305

Serious events: 4 serious events

Other events: 7 other events

Deaths: 0 deaths

Vehicle

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	ISV-305 n=367 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 14 days.	Vehicle n=188 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 14 days.
Nervous system disorders Syncope	0.27% 1/367 • 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, observed up to 41 days. 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., 367 and 188 participants in the ISV-305 and Vehicle arms, respectively).	0.00% 0/188 • 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, observed up to 41 days. 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., 367 and 188 participants in the ISV-305 and Vehicle arms, respectively).
Nervous system disorders Transient global amnesia	0.27% 1/367 • 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, observed up to 41 days. 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., 367 and 188 participants in the ISV-305 and Vehicle arms, respectively).	0.00% 0/188 • 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, observed up to 41 days. 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., 367 and 188 participants in the ISV-305 and Vehicle arms, respectively).
Eye disorders Retinal detachment	0.27% 1/367 • 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, observed up to 41 days. 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., 367 and 188 participants in the ISV-305 and Vehicle arms, respectively).	0.00% 0/188 • 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, observed up to 41 days. 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., 367 and 188 participants in the ISV-305 and Vehicle arms, respectively).
Hepatobiliary disorders Cholecystitis	0.27% 1/367 • 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, observed up to 41 days. 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., 367 and 188 participants in the ISV-305 and Vehicle arms, respectively).	0.00% 0/188 • 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, observed up to 41 days. 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., 367 and 188 participants in the ISV-305 and Vehicle arms, respectively).
Hepatobiliary disorders Cholelithiasis	0.27% 1/367 • 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, observed up to 41 days. 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., 367 and 188 participants in the ISV-305 and Vehicle arms, respectively).	0.00% 0/188 • 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, observed up to 41 days. 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., 367 and 188 participants in the ISV-305 and Vehicle arms, respectively).

Other adverse events

Other adverse events
Measure	ISV-305 n=367 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 14 days.	Vehicle n=188 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 14 days.
Eye disorders Conjunctival hyperaemia	1.9% 7/367 • 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, observed up to 41 days. 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., 367 and 188 participants in the ISV-305 and Vehicle arms, respectively).	2.7% 5/188 • 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, observed up to 41 days. 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., 367 and 188 participants in the ISV-305 and Vehicle arms, respectively).

Additional Information

Head-Clinical Development

Sun Pharma Advanced Research Company Limited

Phone: 912266455645

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place