TOPAZ: Suprachoroidal Injection of Triamcinolone Acetonide With IVT Anti-VEGF in Subjects With Macular Edema Following RVO

• Sponsor: Clearside Biomedical, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03203447
• Collaborator: (none)
• Enrollment: 325
• Locations: 92
• Arms: 2
• Actual Duration (Months): 9.5
• Patients Per Site: 3.5
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This Phase 3, multicenter, randomized, masked, controlled, parallel group study is designed to demonstrate that suprachoroidal (SC) CLS-TA administered with intravitreal (IVT) anti-VEGF agent in subjects with treatment naive RVO is superior to IVT anti-VEGF agent used alone.

Condition or Disease	Intervention/Treatment	Phase
Macular Edema; Retinal Vein Occlusion	Drug: suprachoroidal CLS-TA; Drug: suprachoroidal sham; Drug: Lucentis or Avastin	Phase 3

Detailed Description

A Randomized, Masked, Controlled Trial to Study the Safety and Efficacy of Suprachoroidal CLS-TA With Intravitreal Anti-VEGF Agent in Subjects With Retinal Vein Occlusion

Study Design

• Study Type: Interventional
• Actual Enrollment: 325 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Masked, Controlled Trial To Study The Safety And Efficacy Of Suprachoroidal CLS-TA In Combination With An Intravitreal Anti-VEGF Agent In Subjects With Retinal Vein Occlusion
• Actual Study Start Date: Mar 5, 2018
• Actual Primary Completion Date: Dec 18, 2018
• Actual Study Completion Date: Dec 18, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Active Lucentis (0.5 mg/0.05 mL), IVT injection + CLS-TA (4 mg/0.10 mL), SC injection or Avastin (1.25 mg/0.05 mL), IVT injection + CLS-TA (4 mg/0.10 mL), SC injection	Drug: suprachoroidal CLS-TA; suprachoroidal injection of CLS-TA; Other Names: Triamcinolone acetonide ; Drug: Lucentis or Avastin; IVT anti-VEGF agent. Either a 0.5 mg intravitreal injection of Lucentis or 1.25 mg intravitreal injection of Avastin; Other Names: IVT anti-VEGF agent
Sham Comparator: Control Lucentis (0.5 mg/0.05 mL), IVT injection + sham SC procedure or Avastin (1.25 mg/0.05 mL), IVT injection + sham SC procedure	Drug: suprachoroidal sham; sham suprachoroidal procedure; Drug: Lucentis or Avastin; IVT anti-VEGF agent. Either a 0.5 mg intravitreal injection of Lucentis or 1.25 mg intravitreal injection of Avastin; Other Names: IVT anti-VEGF agent

Outcome Measures

Primary Outcome Measures

1. Proportion of Subjects Demonstrating ≥ 15 Letter Improvement From Baseline in Early Treatment of Diabetic Retinopathy Study (ETDRS) [2 months]

   Best corrected visual acuity (BCVA) refers to the measurement of the best possible vision that can be achieved following refraction or correction. BCVA was assessed following the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol and was measured in the number of letters read correctly on an ETDRS eye chart. An increase from the pre-treatment state in BCVA of 15 letters or more represents a clinically meaningful improvement.

Secondary Outcome Measures

1. Mean Change From Baseline in Best Corrected Visual Acuity [6 months]

   Best corrected visual acuity (BCVA) refers to the measurement of the best possible vision that can be achieved following refraction or correction. BCVA was assessed following the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol and was measured in the number of letters read correctly on an ETDRS eye chart. A positive change from baseline value represents an improvement in vision.

2. Mean Change From Baseline in Central Subfield Thickness [6 months]

   Central subfield thickness (CST) is a diagnostic measurement used in identifying the presence of edema in the circular area 1 mm in diameter centered around the fovea. CST was measured using spectral domain optical coherence tomography (SD-OCT). A masked reading center graded the SD-OCT digital images. A negative change from baseline value represents a reduction in macular edema.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Has a clinical diagnosis of RVO in the study eye

• Has a CST of ≥ 300 µm in the study eye

• Has an ETDRS BCVA score of ≥ 20 letters read and ≤ 70 letters read in the study eye

• Is naïve to local pharmacologic treatment for RVO in the study eye

Exclusion Criteria:

• Any active ocular disease or infection in the study eye other than RVO

• History of glaucoma, intraocular pressure > 21 mmHg or ocular hypertension requiring more than one medication

• Any uncontrolled systemic disease that, in the opinion of the Investigator, would preclude participation in the study

• Any evidence of neovascularization in the study eye

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Retinal Research Institute	Phoenix	Arizona	United States	85053
2	Retina Centers PC	Tucson	Arizona	United States	85704
3	Retina Associates Southwest PC	Tucson	Arizona	United States	85710
4	Win Retina	Arcadia	California	United States	91006
5	Retina Vitreous Medical Group	Beverly Hills	California	United States	90211
6	Retinal Diagnostic Center	Campbell	California	United States	95008
7	Retina Consultants of Orange County	Fullerton	California	United States	92835
8	Macula and Retina Institute	Glendale	California	United States	91203
9	American Institute of Research	Los Angeles	California	United States	90017
10	Retina Vitreous Associates Medical Group Inc	Mountain View	California	United States	94040
11	Stanford University - Byers Eye Institute	Palo Alto	California	United States	94303
12	Retina Consultants of Southern California	Redlands	California	United States	92374
13	Retina Consultants Medical Group Inc	Sacramento	California	United States	95819
14	American Institute of Research	Whittier	California	United States	90603
15	Retina Group of New England, PC	New London	Connecticut	United States	06320
16	Florida Eye Microsurgical Institute	Boynton Beach	Florida	United States	33426
17	Specialty Retina Center	Coral Springs	Florida	United States	33067
18	National Ophthalmic Research Institute	Fort Myers	Florida	United States	33912
19	Center for Retina Care at The Eye Institute	Melbourne	Florida	United States	32904
20	Florida Retina Institute	Orlando	Florida	United States	32806
21	Eye Associates of Pinellas	Pinellas Park	Florida	United States	33782
22	Retina Vitreous Associates of Florida	Saint Petersburg	Florida	United States	33711
23	East Florida Eye Institute EFEI	Stuart	Florida	United States	34994
24	Southern Vitreoretinal Association	Tallahassee	Florida	United States	32308
25	Center for Retina And Macular Disease	Winter Haven	Florida	United States	33880
26	Retina Consultants of Hawaii	'Aiea	Hawaii	United States	96701
27	Gailey Eye Clinic	Bloomington	Illinois	United States	61704
28	University and Macula Associates	Oak Forest	Illinois	United States	60452
29	Prairie Eye Center, Ltd.	Springfield	Illinois	United States	62704
30	Sabates Eye Centers	Leawood	Kansas	United States	66211
31	Vitreo-Retinal Consultants and Surgeons PA	Wichita	Kansas	United States	67214
32	Central Plains Eye MDs	Wichita	Kansas	United States	67226
33	Paducah Retinal Center	Paducah	Kentucky	United States	42001
34	Retina Specialists	Baltimore	Maryland	United States	21204
35	The Retina Care Center	Baltimore	Maryland	United States	21209
36	Retina Group of Washington	Chevy Chase	Maryland	United States	20815
37	Cumberland Valley Retina Consultants	Hagerstown	Maryland	United States	21740
38	The National Retina Institute	Towson	Maryland	United States	21204
39	Ophthalmic Consultants of Boston	Boston	Massachusetts	United States	02114
40	New England Retina Consultants	Springfield	Massachusetts	United States	01107
41	Associated Retinal Consultants PC	Grand Rapids	Michigan	United States	49546
42	Vitreo-Retinal Associates, P.C.	Grand Rapids	Michigan	United States	49546
43	Associated Retinal Consultants P.C.	Royal Oak	Michigan	United States	48073
44	Retina Consultants of Michigan	Southfield	Michigan	United States	48034
45	Associated Retinal Consultants PC	Traverse City	Michigan	United States	49686
46	Retina Associates of St. Louis	Florissant	Missouri	United States	63031
47	Retina Consultants of Nevada	Las Vegas	Nevada	United States	89144
48	Sierra Eye Associates	Reno	Nevada	United States	89502
49	Ophthalmic Consultants of Long Island	Lynbrook	New York	United States	11563
50	Retina Associates of Western New York	Rochester	New York	United States	14620
51	Island Retina	Shirley	New York	United States	11967
52	Retina-Vitreous Surgeons of Central New York	Syracuse	New York	United States	13224
53	Retina Associates of Cleveland Inc	Middleburg Heights	Ohio	United States	44130
54	Dean A. McGee Eye Institute	Oklahoma City	Oklahoma	United States	73104
55	Pennsylvania Retina Specialists PC	Camp Hill	Pennsylvania	United States	17011
56	Black Hills Regional Eye Institute	Rapid City	South Dakota	United States	57701
57	Texas Retina Associates - Arlington	Arlington	Texas	United States	76012
58	Austin Retina Associates	Austin	Texas	United States	78705
59	Retina Research Center	Austin	Texas	United States	78705
60	Texas Retina Associates	Dallas	Texas	United States	75231
61	Retina and Vitreous of Texas, PLLC	Houston	Texas	United States	77025
62	Retina Consultants of Houston, PA	Houston	Texas	United States	77030
63	Valley Retina Institute, PA	McAllen	Texas	United States	78503
64	Retina Specialists	Plano	Texas	United States	75093
65	San Antonio Eye Center	San Antonio	Texas	United States	78215
66	Medical Center Ophthalmology Associates	San Antonio	Texas	United States	78240
67	Retina Associates of South Texas PA	San Antonio	Texas	United States	78240
68	Retina Consultants of Houston, PA	The Woodlands	Texas	United States	77384
69	Strategic Clinical Research Group, LLC	Willow Park	Texas	United States	76087
70	Rocky Mountain Retina Consultants	Salt Lake City	Utah	United States	84107
71	Retina Group of Washington	Fairfax	Virginia	United States	22031
72	West Virginia University Medicine Eye Institute	Morgantown	West Virginia	United States	26506
73	Eye Clinic Albury Wodonga	Albury	New South Wales	Australia	2640
74	Strathfield Retina Clinic	Strathfield	New South Wales	Australia	2135
75	Save Sight Institute, University of Sydney (Sydney Eye Hospital)	Sydney	New South Wales	Australia	2000
76	MH EK Honvédkórház	Budapest		Hungary	1062
77	Raghudeep Eye Hospital	Gujrat	Ahmedabad	India	380052
78	LV Prasad Eye Institute	Hyderabad	Andhra Pradesh	India	500034
79	L V Prasad Eye Institute	Visakhapatnam	Andhra Pradesh	India	530040
80	R.P. Centre, AIIMS	New Delhi	Ansari Nagar	India	110029
81	Narayana Nethralaya	RajajiNagar	Bangalaore	India	560010
82	LV Prasad Eye Institute	Patia	Bhubaneswar	India	751024
83	M&J Western Regional Institute of Ophthalmology	Asarwa	Gujarat	India	380016
84	PBMA's H.V Desai Eye Hospital	Pune	Maharashtra	India	411060
85	Dr Shroff 's Charity Eye Hospital	Delhi	New Delhi	India	758770
86	Regional Institute of Ophthalmology	Bihar	Patna	India	800001
87	B B Eye Foundation VIP	Kolkata	Raghunathpur	India	700059
88	SMS Hospital	Jaipur	Rajasthan	India	302004
89	Aravind Eye Hospital	Madurai	Tamil Nadu	India	625020
90	Jawaharlal Rohatgi Eye Hospital	Kanpur	Uttar Pradesh	India	208005
91	Disha Eye Hospitals Pvt. Ltd.	Kolkata	West Bengal	India	700120
92	Auckland Eye	Auckland		New Zealand	1050

Sponsors and Collaborators

• Clearside Biomedical, Inc.

Investigators

• Study Director: Thomas Ciulla, MD, Chief Medical Officer

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 25, 2018

More Information

Publications

None provided.

• Responsible Party: Clearside Biomedical, Inc.
• ClinicalTrials.gov Identifier: NCT03203447
• Other Study ID Numbers: CLS1003-302
• First Posted: Jun 29, 2017
• Last Update Posted: Apr 23, 2021
• Last Verified: Apr 1, 2021

• 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 Clearside Biomedical, Inc.: RVO; ME; Microneedle; Microinjection; Triamcinolone; Choroid; Choroid injection; Suprachoroidal; Anti-VEGF; Subretinal Fluid; Cystoid Macular Edema; Optical Coherence Tomography; OCT; Central Subfield Thickness; Lucentis; Avastin; Ranibizumab; Bevacizumab; Triamcinolone acetonide
• Additional relevant MeSH terms: Macular Edema; Retinal Vein Occlusion; Edema; Triamcinolone; Triamcinolone Acetonide; Triamcinolone hexacetonide; Bevacizumab; Ranibizumab; Triamcinolone diacetate

Study Results

Participant Flow

Arm/Group Title	Active	Control
Arm/Group Description	Lucentis (0.5 mg/0.05 mL), IVT injection + CLS-TA (4 mg/0.10 mL), SC injection or Avastin (1.25 mg/0.05 mL), IVT injection + CLS-TA (4 mg/0.10 mL), SC injection suprachoroidal CLS-TA: suprachoroidal injection of CLS-TA Lucentis or Avastin: IVT anti-VEGF agent. Either a 0.5 mg intravitreal injection of Lucentis or 1.25 mg intravitreal injection of Avastin	Lucentis (0.5 mg/0.05 mL), IVT injection + sham SC procedure or Avastin (1.25 mg/0.05 mL), IVT injection + sham SC procedure suprachoroidal sham: sham suprachoroidal procedure Lucentis or Avastin: IVT anti-VEGF agent. Either a 0.5 mg intravitreal injection of Lucentis or 1.25 mg intravitreal injection of Avastin
Period Title: Overall Study
STARTED	162	163
COMPLETED	0	0
NOT COMPLETED	162	163

Baseline Characteristics

Arm/Group Title	Active	Control	Total
Arm/Group Description	Lucentis (0.5 mg/0.05 mL), IVT injection + CLS-TA (4 mg/0.10 mL), SC injection or Avastin (1.25 mg/0.05 mL), IVT injection + CLS-TA (4 mg/0.10 mL), SC injection suprachoroidal CLS-TA: suprachoroidal injection of CLS-TA Lucentis or Avastin: IVT anti-VEGF agent. Either a 0.5 mg intravitreal injection of Lucentis or 1.25 mg intravitreal injection of Avastin	Lucentis (0.5 mg/0.05 mL), IVT injection + sham SC procedure or Avastin (1.25 mg/0.05 mL), IVT injection + sham SC procedure suprachoroidal sham: sham suprachoroidal procedure Lucentis or Avastin: IVT anti-VEGF agent. Either a 0.5 mg intravitreal injection of Lucentis or 1.25 mg intravitreal injection of Avastin	Total of all reporting groups
Overall Participants	160	162	322
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	75 46.9%	91 56.2%	166 51.6%
>=65 years	85 53.1%	71 43.8%	156 48.4%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.8 (13.07)	62.6 (12.26)	63.2 (12.66)
Sex: Female, Male (Count of Participants)
Female	79 49.4%	93 57.4%	172 53.4%
Male	81 50.6%	69 42.6%	150 46.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	72 45%	70 43.2%	142 44.1%
Native Hawaiian or Other Pacific Islander	1 0.6%	2 1.2%	3 0.9%
Black or African American	6 3.8%	3 1.9%	9 2.8%
White	77 48.1%	84 51.9%	161 50%
More than one race	2 1.3%	1 0.6%	3 0.9%
Unknown or Not Reported	2 1.3%	2 1.2%	4 1.2%
Region of Enrollment (Count of Participants)
Hungary	2 1.3%	0 0%	2 0.6%
United States	96 60%	98 60.5%	194 60.2%
Australia	2 1.3%	3 1.9%	5 1.6%
India	60 37.5%	61 37.7%	121 37.6%
Type of Retinal Vein Occlusion (Count of Participants)
Branch retinal vein occlusion	90 56.3%	93 57.4%	183 56.8%
Central retinal vein occlusion	70 43.8%	69 42.6%	139 43.2%

Outcome Measures

1. Primary Outcome

Title	Proportion of Subjects Demonstrating ≥ 15 Letter Improvement From Baseline in Early Treatment of Diabetic Retinopathy Study (ETDRS)
Description	Best corrected visual acuity (BCVA) refers to the measurement of the best possible vision that can be achieved following refraction or correction. BCVA was assessed following the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol and was measured in the number of letters read correctly on an ETDRS eye chart. An increase from the pre-treatment state in BCVA of 15 letters or more represents a clinically meaningful improvement.
Time Frame	2 months

Outcome Measure Data

Analysis Population Description

The Intent-to-treat population included all randomized patients. Values for missing data were imputed using last observation carried forward.

Arm/Group Title	Active	Control
Arm/Group Description	Lucentis (0.5 mg/0.05 mL), IVT injection + CLS-TA (4 mg/0.10 mL), SC injection or Avastin (1.25 mg/0.05 mL), IVT injection + CLS-TA (4 mg/0.10 mL), SC injection suprachoroidal CLS-TA: suprachoroidal injection of CLS-TA Lucentis or Avastin: IVT anti-VEGF agent. Either a 0.5 mg intravitreal injection of Lucentis or 1.25 mg intravitreal injection of Avastin	Lucentis (0.5 mg/0.05 mL), IVT injection + sham SC procedure or Avastin (1.25 mg/0.05 mL), IVT injection + sham SC procedure suprachoroidal sham: sham suprachoroidal procedure Lucentis or Avastin: IVT anti-VEGF agent. Either a 0.5 mg intravitreal injection of Lucentis or 1.25 mg intravitreal injection of Avastin
Measure Participants	162	163
Count of Participants [Participants]	64 40%	76 46.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Active, Control
	Comments	Based on a Pearson chi-square test, a total sample size of approximately 460 subjects provided 90% power to detect a difference of 15% between the Active and Control arms assuming the Control arm showed a proportion of 0.50 at 8 weeks. The primary analysis was a test of superiority of the Active arm over the Control arm, and was based on a Cochran-Mantel-Haenszel chi-square test stratified by type of retinal vein occlusion.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.191
	Comments	The a priori threshold for statistical significance was 0.050. Prior to evaluating the results of the CMH test, a Breslow-Day test with Tarone's adjustment was conducted to confirm the homogeneity of the odds ratios between RVO strata.
	Method	Cochran-Mantel-Haenszel
	Comments	The CMH test was stratified by the type of retinal vein occlusion, i.e., branch vs. central.
Method of Estimation	Estimation Parameter	Difference in percentages
	Estimated Value	-7.1
	Confidence Interval	(2-Sided) 95%; -17.9 to 3.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimated value was calculated as the percentage of subjects in the Active arm meeting the primary endpoint minus the percentage of subjects in the Control arm meeting the primary endpoint.

2. Secondary Outcome

Title	Mean Change From Baseline in Best Corrected Visual Acuity
Description	Best corrected visual acuity (BCVA) refers to the measurement of the best possible vision that can be achieved following refraction or correction. BCVA was assessed following the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol and was measured in the number of letters read correctly on an ETDRS eye chart. A positive change from baseline value represents an improvement in vision.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

The Intent-to-treat population included all randomized subjects who received at least one study treatment. Values for missing data were not imputed.

Arm/Group Title	Active	Control
Arm/Group Description	Lucentis (0.5 mg/0.05 mL), IVT injection + CLS-TA (4 mg/0.10 mL), SC injection or Avastin (1.25 mg/0.05 mL), IVT injection + CLS-TA (4 mg/0.10 mL), SC injection suprachoroidal CLS-TA: suprachoroidal injection of CLS-TA Lucentis or Avastin: IVT anti-VEGF agent. Either a 0.5 mg intravitreal injection of Lucentis or 1.25 mg intravitreal injection of Avastin	Lucentis (0.5 mg/0.05 mL), IVT injection + sham SC procedure or Avastin (1.25 mg/0.05 mL), IVT injection + sham SC procedure suprachoroidal sham: sham suprachoroidal procedure Lucentis or Avastin: IVT anti-VEGF agent. Either a 0.5 mg intravitreal injection of Lucentis or 1.25 mg intravitreal injection of Avastin
Measure Participants	160	159
Least Squares Mean (Standard Error) [letters]	13.8 (1.96)	20.7 (1.91)

3. Secondary Outcome

Title	Mean Change From Baseline in Central Subfield Thickness
Description	Central subfield thickness (CST) is a diagnostic measurement used in identifying the presence of edema in the circular area 1 mm in diameter centered around the fovea. CST was measured using spectral domain optical coherence tomography (SD-OCT). A masked reading center graded the SD-OCT digital images. A negative change from baseline value represents a reduction in macular edema.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

The Intent-to-treat population included all randomized subjects who received at least one study treatment. Values for missing data were not imputed.

Arm/Group Title	Active	Control
Arm/Group Description	Lucentis (0.5 mg/0.05 mL), IVT injection + CLS-TA (4 mg/0.10 mL), SC injection or Avastin (1.25 mg/0.05 mL), IVT injection + CLS-TA (4 mg/0.10 mL), SC injection suprachoroidal CLS-TA: suprachoroidal injection of CLS-TA Lucentis or Avastin: IVT anti-VEGF agent. Either a 0.5 mg intravitreal injection of Lucentis or 1.25 mg intravitreal injection of Avastin	Lucentis (0.5 mg/0.05 mL), IVT injection + sham SC procedure or Avastin (1.25 mg/0.05 mL), IVT injection + sham SC procedure suprachoroidal sham: sham suprachoroidal procedure Lucentis or Avastin: IVT anti-VEGF agent. Either a 0.5 mg intravitreal injection of Lucentis or 1.25 mg intravitreal injection of Avastin
Measure Participants	162	159
Least Squares Mean (Standard Error) [microns]	-353.6 (19.60)	-374.7 (19.12)

Adverse Events

Time Frame	Adverse events were collected through follow-up and study completion, approximately 6 months.
Arm/Group Title	Active		Control
Arm/Group Description	Lucentis (0.5 mg/0.05 mL), IVT injection + CLS-TA (4 mg/0.10 mL), SC injection or Avastin (1.25 mg/0.05 mL), IVT injection + CLS-TA (4 mg/0.10 mL), SC injection suprachoroidal CLS-TA: suprachoroidal injection of CLS-TA Lucentis or Avastin: IVT anti-VEGF agent. Either a 0.5 mg intravitreal injection of Lucentis or 1.25 mg intravitreal injection of Avastin		Lucentis (0.5 mg/0.05 mL), IVT injection + sham SC procedure or Avastin (1.25 mg/0.05 mL), IVT injection + sham SC procedure suprachoroidal sham: sham suprachoroidal procedure Lucentis or Avastin: IVT anti-VEGF agent. Either a 0.5 mg intravitreal injection of Lucentis or 1.25 mg intravitreal injection of Avastin
All Cause Mortality
	Active		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/160 (0%)		0/162 (0%)
Serious Adverse Events
	Active		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/160 (0.6%)		3/162 (1.9%)
Cardiac disorders
Cardiac failure congestive	1/160 (0.6%)	1	0/162 (0%)	0
Gastrointestinal disorders
Abdominal pain upper	0/160 (0%)	0	1/162 (0.6%)	1
Infections and infestations
Urinary tract infection	0/160 (0%)	0	1/162 (0.6%)	1
Metabolism and nutrition disorders
Hyperglycaemia	0/160 (0%)	0	1/162 (0.6%)	1
Psychiatric disorders
Mental status changes	0/160 (0%)	0	1/162 (0.6%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	0/160 (0%)	0	1/162 (0.6%)	1
Respiratory failure	1/160 (0.6%)	1	0/162 (0%)	0
Vascular disorders
Deep vein thrombosis	0/160 (0%)	0	1/162 (0.6%)	1
Other (Not Including Serious) Adverse Events
	Active		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/160 (6.9%)		1/162 (0.6%)
Investigations
Intraocular pressure increased	11/160 (6.9%)	14	1/162 (0.6%)	1

Limitations/Caveats

Due to the early termination of the trial by sponsor, 325 of the planned 460 were enrolled. All planned study visits were not completed by all treated subjects; therefore, all planned data was not collected.

More Information

Certain Agreements

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

The institutions and Investigators participating in this study shall have no right to publish or present the results of this study without the prior written consent of Clearside Biomedical, Inc.