Efficacy Study to Evaluate the Effectiveness of 3 Concentrations of SAR 1118 in Allergic Conjunctivitis

• Sponsor: Shire (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00882687
• Collaborator: (none)
• Enrollment: 60
• Location: 1
• Arms: 4
• Actual Duration (Days): 16
• Patients Per Site Per Month: 114.1

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether SAR 1118 at three different concentrations, compared to placebo, is effective in the prevention of the signs and symptoms of allergic conjunctivitis

Condition or Disease	Intervention/Treatment	Phase
Allergic Conjunctivitis	Drug: Lifitegrast; Other: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: A Phase 2, Single Center, Randomized, Double-Masked and Placebo Controlled Study Evaluating the Efficacy of Three Different Concentrations (0.1, 1.0, 5.0%) of SAR 1118 Ophthalmic Solution in a Modified Conjunctival Allergen Challenge (CAC) Model
• Actual Study Start Date: Apr 24, 2009
• Actual Primary Completion Date: May 10, 2009
• Actual Study Completion Date: May 10, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 0.1% Lifitegrast	Drug: Lifitegrast; Ophthalmic Solution; Other Names: SAR 1118
Experimental: 1.0% Lifitegrast	Drug: Lifitegrast; Ophthalmic Solution; Other Names: SAR 1118
Experimental: 5.0% Lifitegrast	Drug: Lifitegrast; Ophthalmic Solution; Other Names: SAR 1118
Placebo Comparator: Placebo	Other: Placebo; Ophthalmic Solution

Outcome Measures

Primary Outcome Measures

1. Ocular Itching at Day 7 (7 Minutes Post Conjunctival Allergen Challenge [CAC 6]) [Baseline to Day 7 (7 minutes post CAC 6)]

   Ocular Itching was evaluated by participants and graded with Ophthalmic Research Associates, Inc. (ORA) Scale with the score ranged from 0 to 4 (0=none; 0.5=intermittent tickle in the cornea; 1=intermittent tickle more than just the cornea; 1.5=intermittent all-over tickling sensation; 2=mild conscious itch without desire to rub; 2.5=moderate, diffuse continuous itch with desire to rub; 3=severe itch with desire to rub; 3.5=severe itch improved with minimal rubbing; 4=incapacitating itch with an irresistible urge to rub) with 0.5 point increments allowed, and lower scores indicates lesser ocular itching. CAC is an initial titration challenge to determine the appropriate allergen and lowest concentration of allergen that produced a positive bilateral allergic response for each subject, defined as ≥ 2 score (0-4 point scale) in ocular itching and conjunctival redness within 10 minutes of the last titration of allergen.

2. Ocular Itching at Day 14 (7 Minutes Post CAC 9) [Baseline to Day 14 (7 minutes post CAC 9)]

   Ocular Itching was evaluated by participants and graded with Ophthalmic Research Associates, Inc. (ORA) Scale with the score ranged from 0 to 4 (0=none; 0.5=intermittent tickle in the cornea; 1=intermittent tickle more than just the cornea; 1.5=intermittent all-over tickling sensation; 2=mild conscious itch without desire to rub; 2.5=moderate, diffuse continuous itch with desire to rub; 3=severe itch with desire to rub; 3.5=severe itch improved with minimal rubbing; 4=incapacitating itch with an irresistible urge to rub) with 0.5 point increments allowed, and lower scores indicates lesser ocular itching.

3. Conjunctival Redness at Day 7 (20 Minutes Post CAC 6) [Baseline to Day 7 (20 minutes post CAC 6)]

   Conjunctival Redness was evaluated by an investigator with slit lamp and graded with ORA Scale with the score ranged from 0 to 4 (0=none; 1=mild-slightly dilated blood vessels; color of vessels is typically pink; can be quadrantal; 2=moderate-more apparent dilation of blood vessels; vessel color is more intense (redder); involves the majority of the vessel bed; 3=severe-numerous and obvious dilated blood vessels; in the absence of chemosis the color is deep red, may be less red or pink in presence of chemosis, is not quadrantic; 4=extremely severe-large, numerous, dilated blood vessels characterized by unusually severe deep red color, regardless of grade of chemosis, which involves the entire vessel bed) with 0.5 point increments allowed, and lower scores indicates reduction in the conjunctival redness.

4. Conjunctival Redness at Day 14 (20 Minutes Post CAC 9) [Baseline to Day 14 (20 minutes post CAC 9)]

   Conjunctival Redness was evaluated by an investigator with slit lamp and graded with ORA Scale with the score ranged from 0 to 4 (0=none; 1=mild-slightly dilated blood vessels; color of vessels is typically pink; can be quadrantal; 2=moderate-more apparent dilation of blood vessels; vessel color is more intense (redder); involves the majority of the vessel bed; 3=severe-numerous and obvious dilated blood vessels; in the absence of chemosis the color is deep red, may be less red or pink in presence of chemosis, is not quadrantic; 4=extremely severe-large, numerous, dilated blood vessels characterized by unusually severe deep red color, regardless of grade of chemosis, which involves the entire vessel bed) with 0.5 point increments allowed, and lower scores indicates reduction in the conjunctival redness.

Secondary Outcome Measures

1. Ocular Itching at Day 6 (CAC 4), 5 (CAC 7) [Baseline to Day 6 (CAC 4), Day 13 (CAC 7) 7 minutes post CAC]

   Ocular Itching was evaluated by participants and graded with Ophthalmic Research Associates, Inc. (ORA) Scale with the score ranged from 0 to 4 (0=none; 0.5=intermittent tickle in the cornea; 1=intermittent tickle more than just the cornea; 1.5=intermittent all-over tickling sensation; 2=mild conscious itch without desire to rub; 2.5=moderate, diffuse continuous itch with desire to rub; 3=severe itch with desire to rub; 3.5=severe itch improved with minimal rubbing; 4=incapacitating itch with an irresistible urge to rub) with 0.5 point increments allowed, and lower scores indicates lesser ocular itching.

2. Conjunctival Redness at Day 6 (CAC 4), 5 (CAC 7) [Baseline to Day 6 (CAC 4), Day 13 (CAC 7) at 20 minutes post CAC]

   Conjunctival Redness was evaluated by an investigator with slit lamp and graded with ORA Scale with the score ranged from 0 to 4 (0=none; 1=mild-slightly dilated blood vessels; color of vessels is typically pink; can be quadrantal; 2=moderate-more apparent dilation of blood vessels; vessel color is more intense (redder); involves the majority of the vessel bed; 3=severe-numerous and obvious dilated blood vessels; in the absence of chemosis the color is deep red, may be less red or pink in presence of chemosis, is not quadrantic; 4=extremely severe-large, numerous, dilated blood vessels characterized by unusually severe deep red color, regardless of grade of chemosis, which involves the entire vessel bed) with 0.5 point increments allowed, and lower scores indicates reduction in the conjunctival redness.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Signed informed consent form and HIPAA document

• Willing and able to comply with all study procedures

• Be at least 18 years of age at the time of enrollment

• 20/40 vision, or better, in each eye

• History of ocular allergies, and a positive skin and ocular allergic reaction to allergens

• A negative urine pregnancy test if female of childbearing potential and must use adequate birth control throughout the study period

Exclusion Criteria:

• Preauricular lymphadenopathy or any ocular condition that could affect study parameters (particularly, glaucoma, diabetic retinopathy, clinically significant blepharitis, follicular conjunctivitis and iritis)

• Have had any ocular infection within the last 30 days

• A positive diagnosis of moderate to severe dry eye syndrome (i.e., requiring daily use of artificial tears)

• Any significant illness that could be expected to interfere with study parameters

• Manifest signs or symptoms of clinically active allergic conjunctivitis in either eye

• Use of any investigational product or device within one month prior to Visit 1 or during the study period

• Concomitant use of any prohibited medication (antihistamines, corticosteroids, all ocular medications or anti-allergic therapies) during the trial or within the washout period

• Any blood donation or significant loss of blood within 56 days of Visit 1

• Any history of autoimmune disease, immunodeficiency disorder, positive HIV, hepatitis B, C, or evidence of acute active hepatitis A (anti-HAV IgM), or organ or bone marrow transplant. Any known history of iritis/uveitis, glaucoma, or other chronic ophthalmologic disorder other than allergic conjunctivitis

• History of laser-assisted in situ keratomileusis (LASIK) or similar type of corneal refractive surgery within 12 months prior to Visit 1, and/or any other ocular surgical procedure within 3 months prior to Visit 1

• Known history of alcohol abuse and/or drug abuse

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ora	Andover	Massachusetts	United States	01810

Sponsors and Collaborators

• Shire

Investigators

• Study Director: Study Director, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Shire
• ClinicalTrials.gov Identifier: NCT00882687
• Other Study ID Numbers: 1118-ACJ-100
• First Posted: Apr 16, 2009
• Last Update Posted: Jun 11, 2021
• Last Verified: Jun 1, 2021

• Additional relevant MeSH terms: Conjunctivitis; Conjunctivitis, Allergic; Lifitegrast

Study Results

Participant Flow

Arm/Group Title	Lifitegrast 0.1%	Lifitegrast 1.0%	Lifitegrast 5.0%	Placebo
Arm/Group Description
Period Title: Overall Study
STARTED	15	15	15	15
COMPLETED	13	13	12	13
NOT COMPLETED	2	2	3	2

Baseline Characteristics

Arm/Group Title	Lifitegrast 0.1%	Lifitegrast 1.0%	Lifitegrast 5.0%	Placebo	Total
Arm/Group Description	Total of all reporting groups
Overall Participants	15	15	15	15	60
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.67 (15.207)	37.67 (12.613)	45.33 (15.891)	39.13 (12.212)	40.95 (14.019)
Sex: Female, Male (Count of Participants)
Female	9 60%	5 33.3%	9 60%	6 40%	29 48.3%
Male	6 40%	10 66.7%	6 40%	9 60%	31 51.7%

Outcome Measures

1. Primary Outcome

Title	Ocular Itching at Day 7 (7 Minutes Post Conjunctival Allergen Challenge [CAC 6])
Description	Ocular Itching was evaluated by participants and graded with Ophthalmic Research Associates, Inc. (ORA) Scale with the score ranged from 0 to 4 (0=none; 0.5=intermittent tickle in the cornea; 1=intermittent tickle more than just the cornea; 1.5=intermittent all-over tickling sensation; 2=mild conscious itch without desire to rub; 2.5=moderate, diffuse continuous itch with desire to rub; 3=severe itch with desire to rub; 3.5=severe itch improved with minimal rubbing; 4=incapacitating itch with an irresistible urge to rub) with 0.5 point increments allowed, and lower scores indicates lesser ocular itching. CAC is an initial titration challenge to determine the appropriate allergen and lowest concentration of allergen that produced a positive bilateral allergic response for each subject, defined as ≥ 2 score (0-4 point scale) in ocular itching and conjunctival redness within 10 minutes of the last titration of allergen.
Time Frame	Baseline to Day 7 (7 minutes post CAC 6)

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population with last observation carried forward (LOCF)

Arm/Group Title	Lifitegrast 0.1%	Lifitegrast 1.0%	Lifitegrast 5.0%	Placebo
Arm/Group Description
Measure Participants	15	15	15	15
Mean (Standard Deviation) [units on a scale]	2.65 (0.731)	2.68 (1.096)	3.07 (0.837)	2.88 (0.410)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lifitegrast 0.1%, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.3235
	Comments
	Method	Wilcoxon rank-sum test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lifitegrast 1.0%, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.9144
	Comments
	Method	Wilcoxon rank-sum test
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Lifitegrast 5.0%, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.3324
	Comments
	Method	Wilcoxon rank-sum test
	Comments

2. Primary Outcome

Title	Ocular Itching at Day 14 (7 Minutes Post CAC 9)
Description	Ocular Itching was evaluated by participants and graded with Ophthalmic Research Associates, Inc. (ORA) Scale with the score ranged from 0 to 4 (0=none; 0.5=intermittent tickle in the cornea; 1=intermittent tickle more than just the cornea; 1.5=intermittent all-over tickling sensation; 2=mild conscious itch without desire to rub; 2.5=moderate, diffuse continuous itch with desire to rub; 3=severe itch with desire to rub; 3.5=severe itch improved with minimal rubbing; 4=incapacitating itch with an irresistible urge to rub) with 0.5 point increments allowed, and lower scores indicates lesser ocular itching.
Time Frame	Baseline to Day 14 (7 minutes post CAC 9)

Outcome Measure Data

Analysis Population Description

ITT population with LOCF

Arm/Group Title	Lifitegrast 0.1%	Lifitegrast 1.0%	Lifitegrast 5.0%	Placebo
Arm/Group Description
Measure Participants	15	15	15	15
Mean (Standard Deviation) [units on a scale]	2.28 (1.043)	2.50 (1.191)	2.63 (0.968)	2.12 (0.737)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lifitegrast 0.1%, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.5846
	Comments
	Method	Wilcoxon rank-sum test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lifitegrast 1.0%, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1493
	Comments
	Method	Wilcoxon rank-sum test
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Lifitegrast 5.0%, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0404
	Comments
	Method	Wilcoxon rank-sum test
	Comments

3. Primary Outcome

Title	Conjunctival Redness at Day 7 (20 Minutes Post CAC 6)
Description	Conjunctival Redness was evaluated by an investigator with slit lamp and graded with ORA Scale with the score ranged from 0 to 4 (0=none; 1=mild-slightly dilated blood vessels; color of vessels is typically pink; can be quadrantal; 2=moderate-more apparent dilation of blood vessels; vessel color is more intense (redder); involves the majority of the vessel bed; 3=severe-numerous and obvious dilated blood vessels; in the absence of chemosis the color is deep red, may be less red or pink in presence of chemosis, is not quadrantic; 4=extremely severe-large, numerous, dilated blood vessels characterized by unusually severe deep red color, regardless of grade of chemosis, which involves the entire vessel bed) with 0.5 point increments allowed, and lower scores indicates reduction in the conjunctival redness.
Time Frame	Baseline to Day 7 (20 minutes post CAC 6)

Outcome Measure Data

Analysis Population Description

ITT population with LOCF

Arm/Group Title	Lifitegrast 0.1%	Lifitegrast 1.0%	Lifitegrast 5.0%	Placebo
Arm/Group Description
Measure Participants	15	15	15	15
Mean (Standard Deviation) [units on a scale]	2.27 (0.458)	2.48 (0.406)	2.57 (0.477)	2.52 (0.427)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lifitegrast 0.1%, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0578
	Comments
	Method	Wilcoxon rank-sum test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lifitegrast 1.0%, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.8988
	Comments
	Method	Wilcoxon rank-sum test
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Lifitegrast 5.0%, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.4709
	Comments
	Method	Wilcoxon rank-sum test
	Comments

4. Primary Outcome

Title	Conjunctival Redness at Day 14 (20 Minutes Post CAC 9)
Description	Conjunctival Redness was evaluated by an investigator with slit lamp and graded with ORA Scale with the score ranged from 0 to 4 (0=none; 1=mild-slightly dilated blood vessels; color of vessels is typically pink; can be quadrantal; 2=moderate-more apparent dilation of blood vessels; vessel color is more intense (redder); involves the majority of the vessel bed; 3=severe-numerous and obvious dilated blood vessels; in the absence of chemosis the color is deep red, may be less red or pink in presence of chemosis, is not quadrantic; 4=extremely severe-large, numerous, dilated blood vessels characterized by unusually severe deep red color, regardless of grade of chemosis, which involves the entire vessel bed) with 0.5 point increments allowed, and lower scores indicates reduction in the conjunctival redness.
Time Frame	Baseline to Day 14 (20 minutes post CAC 9)

Outcome Measure Data

Analysis Population Description

ITT population with LOCF

Arm/Group Title	Lifitegrast 0.1%	Lifitegrast 1.0%	Lifitegrast 5.0%	Placebo
Arm/Group Description
Measure Participants	15	15	15	15
Mean (Standard Deviation) [units on a scale]	1.92 (0.686)	2.42 (0.397)	2.38 (0.399)	2.17 (0.652)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lifitegrast 0.1%, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1773
	Comments
	Method	Wilcoxon rank-sum test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lifitegrast 1.0%, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.4222
	Comments
	Method	Wilcoxon rank-sum test
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Lifitegrast 5.0%, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.4326
	Comments
	Method	Wilcoxon rank-sum test
	Comments

5. Secondary Outcome

Title	Ocular Itching at Day 6 (CAC 4), 5 (CAC 7)
Description	Ocular Itching was evaluated by participants and graded with Ophthalmic Research Associates, Inc. (ORA) Scale with the score ranged from 0 to 4 (0=none; 0.5=intermittent tickle in the cornea; 1=intermittent tickle more than just the cornea; 1.5=intermittent all-over tickling sensation; 2=mild conscious itch without desire to rub; 2.5=moderate, diffuse continuous itch with desire to rub; 3=severe itch with desire to rub; 3.5=severe itch improved with minimal rubbing; 4=incapacitating itch with an irresistible urge to rub) with 0.5 point increments allowed, and lower scores indicates lesser ocular itching.
Time Frame	Baseline to Day 6 (CAC 4), Day 13 (CAC 7) 7 minutes post CAC

Outcome Measure Data

Analysis Population Description

ITT population with LOCF

Arm/Group Title	Lifitegrast 0.1%	Lifitegrast 1.0%	Lifitegrast 5.0%	Placebo
Arm/Group Description
Measure Participants	15	15	15	15
Visit 3: 7 minutes post CAC 4	2.83 (0.564)	2.37 (0.886)	3.02 (0.644)	2.82 (0.395)
Visit 5: 7 minutes post CAC 7	2.42 (1.084)	2.62 (0.778)	2.63 (0.972)	2.38 (0.388)

6. Secondary Outcome

Title	Conjunctival Redness at Day 6 (CAC 4), 5 (CAC 7)
Description	Conjunctival Redness was evaluated by an investigator with slit lamp and graded with ORA Scale with the score ranged from 0 to 4 (0=none; 1=mild-slightly dilated blood vessels; color of vessels is typically pink; can be quadrantal; 2=moderate-more apparent dilation of blood vessels; vessel color is more intense (redder); involves the majority of the vessel bed; 3=severe-numerous and obvious dilated blood vessels; in the absence of chemosis the color is deep red, may be less red or pink in presence of chemosis, is not quadrantic; 4=extremely severe-large, numerous, dilated blood vessels characterized by unusually severe deep red color, regardless of grade of chemosis, which involves the entire vessel bed) with 0.5 point increments allowed, and lower scores indicates reduction in the conjunctival redness.
Time Frame	Baseline to Day 6 (CAC 4), Day 13 (CAC 7) at 20 minutes post CAC

Outcome Measure Data

Analysis Population Description

ITT population with LOCF

Arm/Group Title	Lifitegrast 0.1%	Lifitegrast 1.0%	Lifitegrast 5.0%	Placebo
Arm/Group Description
Measure Participants	15	15	15	15
Visit 3: 20 minutes post CAC 4	1.82 (0.594)	2.15 (0.725)	2.25 (0.605)	2.25 (0.433)
Visit 5: 20 minutes post CAC 7	1.37 (0.911)	2.15 (0.749)	1.62 (1.026)	1.77 (0.863)

Adverse Events

Time Frame	Up to Day 16
Arm/Group Title	Lifitegrast 0.1%		Lifitegrast 1.0%		Lifitegrast 5.0%		Placebo
Arm/Group Description
All Cause Mortality
	Lifitegrast 0.1%		Lifitegrast 1.0%		Lifitegrast 5.0%		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Lifitegrast 0.1%		Lifitegrast 1.0%		Lifitegrast 5.0%		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/15 (0%)		0/15 (0%)		1/15 (6.7%)
Injury, poisoning and procedural complications
Traumatic haematoma	0/15 (0%)	0	0/15 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
Other (Not Including Serious) Adverse Events
	Lifitegrast 0.1%		Lifitegrast 1.0%		Lifitegrast 5.0%		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/15 (40%)		7/15 (46.7%)		12/15 (80%)		6/15 (40%)
Eye disorders
Eye Disorders	4/15 (26.7%)	7	6/15 (40%)	11	9/15 (60%)	16	0/15 (0%)	0
General disorders
General Discomfort and Administration Site Conditions	4/15 (26.7%)	5	2/15 (13.3%)	3	6/15 (40%)	10	6/15 (40%)	7

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.