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

• Sponsor: Sun Pharmaceutical Industries Limited (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01543490
• Collaborator: (none)
• Enrollment: 558
• Location: 1
• Arms: 2
• Actual Duration (Months): 22.2
• Patients Per Site Per Month: 25.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the clinical efficacy and safety of ISV-305 (Dexamethasone in DuraSite® 2) compared to Vehicle in the treatment of subjects with active, symptomatic Blepharitis.

Condition or Disease	Intervention/Treatment	Phase
Active, Symptomatic Blepharitis	Drug: ISV-305; Other: Vehicle	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 558 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Multicenter, Randomized, Double-Masked, Parallel-Group, Comparative Study to Evaluate the Clinical Efficacy and Safety of ISV-305 (0.1% Dexamethasone) Compared to Vehicle in the Treatment of Subjects With Blepharitis
• Actual Study Start Date: Mar 30, 2018
• Actual Primary Completion Date: Feb 4, 2020
• Actual Study Completion Date: Feb 4, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ISV-305 0.1% dexamethasone in DuraSite® 2	Drug: ISV-305; Dexamethasone in DuraSite® 2 twice daily for 2 weeks
Placebo Comparator: Vehicle DuraSite® 2 vehicle	Other: Vehicle; Vehicle twice daily for 2 weeks

Outcome Measures

Primary Outcome Measures

1. 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 [Day 15]

   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.

Secondary Outcome Measures

1. Number of Participants With Complete Resolution of Eyelid Irritation (Last Observation Carried Forward [LOCF]) on Day 15 in ITT Population [Day 15]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Year and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Are at least 1 years of age and have a clinical diagnosis of active, symptomatic blepharitis

• Signature of the subject or parent(s) or legally authorized representative on the Informed Consent Form, and when appropriate the minor's assent in accordance with local regulations

• Are willing and able to follow all instructions and attend all study visits (this applies to parent or caregiver for subjects too young to self-apply investigational product)

• Are willing to avoid disallowed medication for the duration of the study

• If female is of childbearing potential, agree to and submit a urine sample for pregnancy testing (prior to enrollment and at the end of the study) and use effective contraception for the duration of the study

• Male subjects whose female partners are not post-menopausal must agree to one of the following: 1) completely abstain from sexual intercourse, 2) use a barrier method (condoms) with spermicide during sexual intercourse for the duration of the study, 3) provide documentation for having had a vasectomy (with documented infertility)

• Additional inclusion criteria also apply

Exclusion Criteria:

• Have known sensitivity or poor tolerance to any component of the study drugs

• Have had eyelid surgery in the study eye within twelve (12) months prior to Visit 1 or plan to have eyelid surgery during the study

• Have an acute ocular infection (bacterial, viral or fungal) or active ocular inflammation other than blepharitis in the study eye

• Have used topical medications on the eyelids or topical ophthalmic corticosteroid medications or systemic use of a corticosteroid mediation within 14 days prior to dosing and/or plan to use them throughout the duration of the study

• Be currently pregnant, nursing, or planning a pregnancy; or be a woman who has a positive urine pregnancy test

• Have prior (within 30 days prior to dosing) or anticipated concurrent use of an investigational drug or device

• Have a condition or a situation which, in the investigator's opinion, may put the subject at increased risk, confound study data, or interfere significantly with the subject's study participation

• Additional exclusion criteria also apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Research Center	Newport Beach	California	United States	92663

Sponsors and Collaborators

• Sun Pharmaceutical Industries Limited

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Jun 22, 2017
• Statistical Analysis Plan - Jun 24, 2020

More Information

Publications

None provided.

• Responsible Party: Sun Pharmaceutical Industries Limited
• ClinicalTrials.gov Identifier: NCT01543490
• Other Study ID Numbers: C-12-305-001
• First Posted: Mar 5, 2012
• Last Update Posted: Nov 19, 2021
• Last Verified: Nov 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Blepharitis

Study Results

Participant Flow

Arm/Group Title	ISV-305	Vehicle
Arm/Group Description	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 (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.
Period Title: Overall Study
STARTED	368	190
COMPLETED	352	185
NOT COMPLETED	16	5

Baseline Characteristics

Arm/Group Title	ISV-305	Vehicle	Total
Arm/Group Description	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 (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 of all reporting groups
Overall Participants	368	190	558
Age, Customized (Count of Participants)
< 17 years	0 0%	0 0%	0 0%
17 to < 65 years	146 39.7%	66 34.7%	212 38%
≥ 65 years	222 60.3%	124 65.3%	346 62%
Sex: Female, Male (Count of Participants)
Female	209 56.8%	107 56.3%	316 56.6%
Male	159 43.2%	83 43.7%	242 43.4%
Race/Ethnicity, Customized (Count of Participants)
African American or Black	20 5.4%	2 1.1%	22 3.9%
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	6 1.6%	3 1.6%	9 1.6%
White	334 90.8%	184 96.8%	518 92.8%
Native Hawaiian or Other Pacific Islander	2 0.5%	0 0%	2 0.4%
Mixed	1 0.3%	0 0%	1 0.2%
Other	5 1.4%	1 0.5%	6 1.1%
Region of Enrollment (Count of Participants)
United States	368 100%	190 100%	558 100%

Outcome Measures

1. Primary Outcome

Title	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
Description	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.
Time Frame	Day 15

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	ISV-305	Vehicle
Arm/Group Description	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 (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.
Measure Participants	353	185
Responders	276 75%	129 67.9%
Non-responders	77 20.9%	56 29.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ISV-305, Vehicle
	Comments
	Type of Statistical Test	Superiority
	Comments	Statistical hypotheses testing for the primary efficacy endpoint was 2-sided and performed using a significance (alpha) level of 0.05.
Statistical Test of Hypothesis	p-Value	0.0354
	Comments	The p-value was from a 2-sided Fisher's exact test.
	Method	Fisher Exact
	Comments	The point estimate of treatment effect (ISV-305 compared with Vehicle) was reported using Fisher's exact test.
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	8.5
	Confidence Interval	(2-Sided) 95%; 0.2 to 16.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.03
	Estimation Comments	The risk difference was obtained by taking the difference in proportions (ISV-305 minus Vehicle). A 2-sided exact unconditional 95% confidence interval (CI) was calculated.

2. Secondary Outcome

Title	Number of Participants With Complete Resolution of Eyelid Irritation (Last Observation Carried Forward [LOCF]) on Day 15 in ITT Population
Description	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.
Time Frame	Day 15

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	ISV-305	Vehicle
Arm/Group Description	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 (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.
Measure Participants	368	190
With Complete Resolution	127 34.5%	52 27.4%
Without Complete Resolution	241 65.5%	138 72.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ISV-305, Vehicle
	Comments
	Type of Statistical Test	Superiority
	Comments	Statistical hypotheses testing for the secondary efficacy endpoint was 2-sided and performed using a significance (alpha) level of 0.05, and missing data imputed using the LOCF approach.
Statistical Test of Hypothesis	p-Value	0.1036
	Comments	The p-value was from a 2-sided Fisher's exact test.
	Method	Fisher Exact
	Comments	The point estimate of treatment effect (ISV-305 compared with Vehicle) was reported using Fisher's exact test.
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	7.1
	Confidence Interval	(2-Sided) 95%; -1.3 to 15.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.07
	Estimation Comments	The risk difference was obtained by taking the difference in proportions (ISV-305 minus Vehicle). A 2-sided exact unconditional 95% CI was calculated.

Adverse Events

Time Frame	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.
Adverse Event Reporting Description	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).
Arm/Group Title	ISV-305		Vehicle
Arm/Group Description	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 (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.
All Cause Mortality
	ISV-305		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/367 (0%)		0/188 (0%)
Serious Adverse Events
	ISV-305		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/367 (1.1%)		0/188 (0%)
Eye disorders
Retinal detachment	1/367 (0.3%)		0/188 (0%)
Hepatobiliary disorders
Cholecystitis	1/367 (0.3%)		0/188 (0%)
Cholelithiasis	1/367 (0.3%)		0/188 (0%)
Nervous system disorders
Syncope	1/367 (0.3%)		0/188 (0%)
Transient global amnesia	1/367 (0.3%)		0/188 (0%)
Other (Not Including Serious) Adverse Events
	ISV-305		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/367 (1.9%)		5/188 (2.7%)
Eye disorders
Conjunctival hyperaemia	7/367 (1.9%)		5/188 (2.7%)

Limitations/Caveats

[Not Specified]

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.