SURPH: A Study of the Response to AG-86893 in Patients With Pterygium Hyperemia

• Sponsor: Allgenesis Biotherapeutics Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03533244
• Collaborator: (none)
• Enrollment: 64
• Locations: 6
• Arms: 3
• Actual Duration (Months): 12.5
• Patients Per Site: 10.7
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

A pterygium is a wing-shaped, benign tissue growth which forms on the surface of the conjunctiva and grows towards the cornea. It can eventually lead to vision impairment. The precise cause of pterygium formation is unknown but new blood vessel growth and fibroblastic structures are characteristics of the disease. AG-86893 is an eye drop being developed to treat hyperemia (redness) and growth of the pterygium.

Hypothesis

1. AG-86893 dosed three times daily for 28 consecutive days has an acceptable safety profile as measured by the incidence and severity of adverse events (AEs) compared with vehicle

2. At least 1 concentration of AG-86893 is effective, as measured by the mean change from baseline in conjunctival hyperemia (redness), compared with vehicle

Condition or Disease	Intervention/Treatment	Phase
Pterygium	Drug: 0.1% AG-86893 Eye Drops; Drug: 0.3% AG-86893 Eye Drops; Drug: Vehicle Eye Drops	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 64 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Prospective, Randomized, Double-Masked, Phase 2 Study Evaluating the Safety, Tolerability, and Efficacy of Topical AG-86893 in Patients With Pterygium
• Actual Study Start Date: Oct 11, 2018
• Actual Primary Completion Date: Sep 5, 2019
• Actual Study Completion Date: Oct 25, 2019

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Vehicle Eye Drops One drop, three times daily to the study eye for 28 days	Drug: Vehicle Eye Drops; One drop, three times daily to the study eye for 28 days
Experimental: 0.1% AG-86893 Eye Drops One drop, three times daily to the study eye for 28 days	Drug: 0.1% AG-86893 Eye Drops; One drop, three times daily to the study eye for 28 days
Experimental: 0.3% AG-86893 Eye Drops One drop, three times daily to the study eye for 28 days	Drug: 0.3% AG-86893 Eye Drops; One drop, three times daily to the study eye for 28 days

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Overall Conjunctival Hyperemia Score [Baseline and Day 28]

   Assessed by digital ocular photography; each quadrant of the eye (superior, inferior, nasal, temporal) will be scored using a 5-point scale (0 = none, 1 = mild, 2 = moderate, 3 = severe, and 4 = very severe) and graded by a reading center. The overall conjunctival score is the average of the four quadrants. Assessments are made by subtracting the score at Baseline from the score on Day 28. An increase in value indicates worsening of hyperemia, while a decrease indicates improvement.

Secondary Outcome Measures

1. Change From Baseline in Conjunctival Hyperemia Score in the Quadrant With the Pterygium [Baseline and Day 28]

   Assessed by digital ocular photography; the quadrant with the pterygium will be scored using a 5-point scale (0 = none, 1 = mild, 2 = moderate, 3 = severe, and 4 = very severe) and graded by a reading center. Assessments are made by subtracting the score at Baseline from the score on Day 28. An increase in value indicates worsening of hyperemia, while a decrease indicates improvement.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Good health with no clinically significant findings based on the medical history, electrocardiogram, vital signs, blood chemistry, hematology, and urinalysis findings, as determined by the investigator

• Females of childbearing potential must have a negative pregnancy test at baseline and must be on established, adequate contraception and males must use condoms if their partner is of childbearing potential and their female partner should also use an additional effective means of contraception, or they must agree to abstain from sexual intercourse with a female partner for the duration of the study; contraception should be continued for 3 months after the last dose.

• Presence of pterygium with associated conjunctival hyperemia (redness) of grade ≥2 as assessed by a central reading center.

Exclusion Criteria:

• History or presence of any ocular diseases other than pterygium or its sequelae (after-effects), including neoplasia (uncontrolled overgrowth)

• Diagnosis of ocular hypertension or glaucoma requiring use of intraocular pressure-lowering medication

• Use of contact lenses during the study in the study eye

• History or evidence of ocular surgeries in the study eye at any time

• History of liver dysfunction or current abnormal liver enzymes

• Pregnancy, plans for pregnancy, or breastfeeding during the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	M.T. Coroneo Pty Ltd	Randwick	New South Wales	Australia
2	H2Vision Centre	Sippy Downs	Queensland	Australia
3	Bendigo Eye Clinic	Bendigo	Victoria	Australia
4	Essendon Eye Clinic	Essendon	Victoria	Australia
5	The Geelong Eye Centre	Waurn Ponds	Victoria	Australia
6	Lions Eye Institute	Nedlands	Western Australia	Australia

Sponsors and Collaborators

• Allgenesis Biotherapeutics Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Statistical Analysis Plan - Nov 5, 2019
• Study Protocol - Mar 20, 2019

More Information

Publications

None provided.

• Responsible Party: Allgenesis Biotherapeutics Inc.
• ClinicalTrials.gov Identifier: NCT03533244
• Other Study ID Numbers: P2-86893-001
• First Posted: May 23, 2018
• Last Update Posted: Nov 6, 2020
• Last Verified: Jan 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Allgenesis Biotherapeutics Inc.: Hyperemia
• Additional relevant MeSH terms: Pterygium; Ophthalmic Solutions

Study Results

Participant Flow

Arm/Group Title	Vehicle Eye Drops	0.1% AG-86893 Eye Drops	0.3% AG-86893 Eye Drops
Arm/Group Description	One drop, three times daily to the study eye for 28 days Vehicle Eye Drops: One drop, three times daily to the study eye for 28 days	One drop, three times daily to the study eye for 28 days 0.1% AG-86893 Eye Drops: One drop, three times daily to the study eye for 28 days	One drop, three times daily to the study eye for 28 days 0.3% AG-86893 Eye Drops: One drop, three times daily to the study eye for 28 days
Period Title: Overall Study
STARTED	20	22	22
COMPLETED	18	21	22
NOT COMPLETED	2	1	0

Baseline Characteristics

Arm/Group Title	Vehicle Eye Drops	0.1% AG-86893 Eye Drops	0.3% AG-86893 Eye Drops	Total
Arm/Group Description	One drop, three times daily to the study eye for 28 days Vehicle Eye Drops: One drop, three times daily to the study eye for 28 days	One drop, three times daily to the study eye for 28 days 0.1% AG-86893 Eye Drops: One drop, three times daily to the study eye for 28 days	One drop, three times daily to the study eye for 28 days 0.3% AG-86893 Eye Drops: One drop, three times daily to the study eye for 28 days	Total of all reporting groups
Overall Participants	20	22	22	64
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.8 (12.4)	54.7 (11.9)	49.0 (10.7)	51.2 (11.8)
Sex: Female, Male (Count of Participants)
Female	10 50%	5 22.7%	11 50%	26 40.6%
Male	10 50%	17 77.3%	11 50%	38 59.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	1 4.5%	1 4.5%	2 3.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	18 90%	21 95.5%	19 86.4%	58 90.6%
More than one race	1 5%	0 0%	0 0%	1 1.6%
Unknown or Not Reported	1 5%	0 0%	2 9.1%	3 4.7%
Region of Enrollment (Count of Participants)
Australia	20 100%	22 100%	22 100%	64 100%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Overall Conjunctival Hyperemia Score
Description	Assessed by digital ocular photography; each quadrant of the eye (superior, inferior, nasal, temporal) will be scored using a 5-point scale (0 = none, 1 = mild, 2 = moderate, 3 = severe, and 4 = very severe) and graded by a reading center. The overall conjunctival score is the average of the four quadrants. Assessments are made by subtracting the score at Baseline from the score on Day 28. An increase in value indicates worsening of hyperemia, while a decrease indicates improvement.
Time Frame	Baseline and Day 28

Outcome Measure Data

Analysis Population Description

modified intent-to-treat (mITT)

Arm/Group Title	Vehicle Eye Drops	0.1% AG-86893 Eye Drops	0.3% AG-86893 Eye Drops
Arm/Group Description	One drop, three times daily to the study eye for 28 days Vehicle Eye Drops: One drop, three times daily to the study eye for 28 days	One drop, three times daily to the study eye for 28 days 0.1% AG-86893 Eye Drops: One drop, three times daily to the study eye for 28 days	One drop, three times daily to the study eye for 28 days 0.3% AG-86893 Eye Drops: One drop, three times daily to the study eye for 28 days
Measure Participants	18	22	22
Least Squares Mean (Standard Error) [score on a scale]	-0.056 (0.120)	-0.330 (0.109)	-0.352 (0.109)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vehicle Eye Drops, 0.3% AG-86893 Eye Drops
	Comments	An empirical sample size estimation was used as this was an exploratory study. The null hypothesis is that there is no difference between AG-86893 and AG-86893 Vehicle. It is expected that the active group is at least 50% better than the vehicle.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.218
	Comments	To reserve the family-wise error rate, the main treatment effect will be first assessed at the global level at alpha = 0.05. If this is significant, then pairwise comparisons will be conducted using the Bonferroni adjustment for multiplicity.
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Vehicle Eye Drops, 0.1% AG-86893 Eye Drops
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.290
	Comments
	Method	Mixed Models Analysis
	Comments

2. Secondary Outcome

Title	Change From Baseline in Conjunctival Hyperemia Score in the Quadrant With the Pterygium
Description	Assessed by digital ocular photography; the quadrant with the pterygium will be scored using a 5-point scale (0 = none, 1 = mild, 2 = moderate, 3 = severe, and 4 = very severe) and graded by a reading center. Assessments are made by subtracting the score at Baseline from the score on Day 28. An increase in value indicates worsening of hyperemia, while a decrease indicates improvement.
Time Frame	Baseline and Day 28

Outcome Measure Data

Analysis Population Description

Per protocol (PP)

Arm/Group Title	Vehicle Eye Drops	0.1% AG-86893 Eye Drops	0.3% AG-86893 Eye Drops
Arm/Group Description	One drop, three times daily to the study eye for 28 days Vehicle Eye Drops: One drop, three times daily to the study eye for 28 days	One drop, three times daily to the study eye for 28 days 0.1% AG-86893 Eye Drops: One drop, three times daily to the study eye for 28 days	One drop, three times daily to the study eye for 28 days 0.3% AG-86893 Eye Drops: One drop, three times daily to the study eye for 28 days
Measure Participants	18	21	22
Least Squares Mean (Standard Error) [score on a scale]	-0.111 (0.153)	-0.429 (0.142)	-0.500 (0.138)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vehicle Eye Drops, 0.3% AG-86893 Eye Drops
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.193
	Comments
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Vehicle Eye Drops, 0.1% AG-86893 Eye Drops
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.399
	Comments
	Method	Mixed Models Analysis
	Comments

3. Post-Hoc Outcome

Title	Percent of Patients With a 1-point Decrease in Hyperemia Score in the Quadrant With the Pterygium
Description	Assessed by digital ocular photography; the quadrant with the pterygium will be scored using a 5-point scale and graded by a reading center. A 1-point reduction in hyperemia score is considered clinically meaningful.
Time Frame	Day 28

Outcome Measure Data

Analysis Population Description

Per protocol (PP)

Arm/Group Title	Vehicle Eye Drops	0.1% AG-86893 Eye Drops	0.3% AG-86893 Eye Drops
Arm/Group Description	One drop, three times daily to the study eye for 28 days Vehicle Eye Drops: One drop, three times daily to the study eye for 28 days	One drop, three times daily to the study eye for 28 days 0.1% AG-86893 Eye Drops: One drop, three times daily to the study eye for 28 days	One drop, three times daily to the study eye for 28 days 0.3% AG-86893 Eye Drops: One drop, three times daily to the study eye for 28 days
Measure Participants	18	21	22
Count of Participants [Participants]	3 15%	11 50%	12 54.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vehicle Eye Drops, 0.3% AG-86893 Eye Drops
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.015
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Vehicle Eye Drops, 0.1% AG-86893 Eye Drops
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.022
	Comments
	Method	Fisher Exact
	Comments

Adverse Events

Time Frame	Adverse events were monitored for each patient until Day 84 (exit).
Arm/Group Title	Vehicle Eye Drops		0.1% AG-86893 Eye Drops		0.3% AG-86893 Eye Drops
Arm/Group Description	One drop, three times daily to the study eye for 28 days Vehicle Eye Drops: One drop, three times daily to the study eye for 28 days		One drop, three times daily to the study eye for 28 days 0.1% AG-86893 Eye Drops: One drop, three times daily to the study eye for 28 days		One drop, three times daily to the study eye for 28 days 0.3% AG-86893 Eye Drops: One drop, three times daily to the study eye for 28 days
All Cause Mortality
	Vehicle Eye Drops		0.1% AG-86893 Eye Drops		0.3% AG-86893 Eye Drops
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/22 (0%)		0/22 (0%)
Serious Adverse Events
	Vehicle Eye Drops		0.1% AG-86893 Eye Drops		0.3% AG-86893 Eye Drops
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/22 (0%)		0/22 (0%)
Other (Not Including Serious) Adverse Events
	Vehicle Eye Drops		0.1% AG-86893 Eye Drops		0.3% AG-86893 Eye Drops
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/20 (25%)		5/22 (22.7%)		15/22 (68.2%)
Ear and labyrinth disorders
Influenza	1/20 (5%)		0/22 (0%)		0/22 (0%)
Nasopharyngitis	1/20 (5%)		0/22 (0%)		0/22 (0%)
Pneumonia	1/20 (5%)		0/22 (0%)		0/22 (0%)
Viral upper respiratory tract infection	1/20 (5%)		0/22 (0%)		0/22 (0%)
Eye disorders
Conjunctival Discoloration	0/20 (0%)		1/22 (4.5%)		10/22 (45.5%)
Vision blurred	1/20 (5%)		1/22 (4.5%)		4/22 (18.2%)
Dry eye	0/20 (0%)		0/22 (0%)		2/22 (9.1%)
Eye pruritis	1/20 (5%)		2/22 (9.1%)		0/22 (0%)
Eye pain	1/20 (5%)		0/22 (0%)		1/22 (4.5%)
Ocular hyperaemia	1/20 (5%)		0/22 (0%)		0/22 (0%)
Blepharitis	1/20 (5%)		0/22 (0%)		0/22 (0%)
Episcleritis	1/20 (5%)		0/22 (0%)		0/22 (0%)
Lacrimation increased	2/20 (10%)		1/22 (4.5%)		0/22 (0%)
Visual impairment	1/20 (5%)		0/22 (0%)		0/22 (0%)
Skin and subcutaneous tissue disorders
Dermatitis allergic	1/20 (5%)		0/22 (0%)		0/22 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT 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.