DOGWOOD: Suprachoroidal Injection of Triamcinolone Acetonide in Subjects With Macular Edema Following Non-Infectious Uveitis

• Sponsor: Clearside Biomedical, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02255032
• Collaborator: (none)
• Enrollment: 22
• Locations: 11
• Arms: 2
• Duration (Months): 15
• Patients Per Site: 2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The study is designed to evaluate the safety and efficacy of triamcinolone acetonide, CLS-TA, in subjects with macular edema following non-infectious uveitis. A single suprachoroidal injection of one of two doses of CLS-TA will each be evaluated in subjects with macular edema following non-infectious uveitis.

Condition or Disease	Intervention/Treatment	Phase
Uveitis; Macular Edema; Uveitis, Posterior; Uveitis, Anterior; Panuveitis; Uveitis, Intermediate	Drug: 4 mg CLS-TA; Drug: 0.8 mg CLS-TA	Phase 2

Detailed Description

This is a Phase 2, randomized, masked, multicenter study to assess the safety and efficacy of two different doses of CLS-TA in the treatment of subjects with macular edema following non-infectious uveitis. Each subject will receive a single suprachoroidal injection of CLS-TA.

The subjects enrolled in this study will be chosen from subjects with macular edema following non-infectious uveitis. A single injection will be administered via the Clearside microinjector into the suprachoroidal space. The dose injected will either be 4 mg or 0.8 mg of CLS-TA in a total volume of 100 μL. The dose they receive will depend on what their randomization code dictates.

Subjects will be monitored for safety and efficacy for approximately 8 weeks following treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 22 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Masked, Multicenter Study to Assess the Safety and Efficacy of CLS-TA, Triamcinolone Acetonide Injectable Suspension in the Treatment of Subjects With Macular Edema Following Uveitis
• Study Start Date: Oct 1, 2014
• Actual Primary Completion Date: Dec 1, 2015
• Actual Study Completion Date: Jan 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 4 mg CLS-TA Single unilateral, suprachoroidal injection of 40 mg/mL (4 mg in 100 µL) of CLS-TA	Drug: 4 mg CLS-TA; 40 mg/mL CLS-TA, Clearside's formulation of TA (CLS-TA, triamcinolone acetonide injectable suspension)
Experimental: 0.8 mg CLS-TA Single unilateral, suprachoroidal injection of 8 mg/mL (0.8 mg in 100 µL) of CLS-TA	Drug: 0.8 mg CLS-TA; 8 mg/mL CLS-TA, Clearside's formulation of TA (CLS-TA, triamcinolone acetonide injectable suspension)

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Central Subfield Thickness, Measured Using Optical Coherence Tomography, After Treatment With CLS-TA in Subjects With Macular Edema Following Uveitis [2 months]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• diagnosis of noninfectious uveitis

• diagnosis of macular edema associated with noninfectious uveitis

Exclusion Criteria:

• any ocular trauma within the immediate 6 months prior to treatment

• any photocoagulation or cryotherapy in the 6 months prior to treatment

• any IVT injection of anti-VEGF treatment in the 2 months prior to treatment

• any eye diseases other than uveitis and ME that could compromise central visual acuity

• any previous suprachoroidal injection of triamcinolone acetonide in the study eye

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Miami	Florida	United States	33136
2		Atlanta	Georgia	United States	30322
3		Chicago	Illinois	United States	60611
4		Boston	Massachusetts	United States	02114
5		Waltham	Massachusetts	United States	02451
6		Omaha	Nebraska	United States	68105
7		New York	New York	United States	10021
8		Winston-Salem	North Carolina	United States	27157
9		Fargo	North Dakota	United States	58103
10		Cleveland	Ohio	United States	44195
11		Dallas	Texas	United States	75231

Sponsors and Collaborators

• Clearside Biomedical, Inc.

Investigators

• Study Director: Thomas Ciulla, MD, Clearside Biomedical, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Clearside Biomedical, Inc.
• ClinicalTrials.gov Identifier: NCT02255032
• Other Study ID Numbers: CLS1001-201
• First Posted: Oct 2, 2014
• Last Update Posted: Feb 8, 2021
• Last Verified: Jan 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Clearside Biomedical, Inc.: uveitis; macular edema; UME; posterior uveitis; anterior uveitis; panuveitis; intermediate uveitis; noninfectious uveitis; triamcinolone acetonide; suprachoroidal space; injection; microneedle; intravitreal injection; corticosteroid; CME; choroid; retina; microinjection; SCS
• Additional relevant MeSH terms: Macular Edema; Uveitis; Panuveitis; Uveitis, Posterior; Uveitis, Intermediate; Pars Planitis; Uveitis, Anterior; Edema

Study Results

Participant Flow

Arm/Group Title	4 mg CLS-TA	0.8 mg CLS-TA
Arm/Group Description	Single unilateral, suprachoroidal injection of 40 mg/mL (4 mg in 100 µL) of CLS-TA 4 mg CLS-TA: 4 mg/mL CLS-TA, Clearside's formulation of TA (CLS-TA, triamcinolone acetonide injectable suspension)	Single unilateral, suprachoroidal injection of 8 mg/mL (0.8 mg in 100 µL) of CLS-TA 0.8 mg CLS-TA: 0.8 mg/mL CLS-TA, Clearside's formulation of TA (CLS-TA, triamcinolone acetonide injectable suspension)
Period Title: Overall Study
STARTED	17	5
COMPLETED	17	5
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	4 mg CLS-TA	0.8 mg CLS-TA	Total
Arm/Group Description	Single unilateral, suprachoroidal injection of 40 mg/mL (4 mg in 100 µL) of CLS-TA 4 mg CLS-TA: 4 mg/mL CLS-TA, Clearside's formulation of TA (CLS-TA, triamcinolone acetonide injectable suspension)	Single unilateral, suprachoroidal injection of 8 mg/mL (0.8 mg in 100 µL) of CLS-TA 0.8 mg CLS-TA: 0.8 mg/mL CLS-TA, Clearside's formulation of TA (CLS-TA, triamcinolone acetonide injectable suspension)	Total of all reporting groups
Overall Participants	17	5	22
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	13 76.5%	4 80%	17 77.3%
>=65 years	4 23.5%	1 20%	5 22.7%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	52.2 (19.65)	51.8 (16.87)	52.1 (18.67)
Sex: Female, Male (Count of Participants)
Female	8 47.1%	4 80%	12 54.5%
Male	9 52.9%	1 20%	10 45.5%
Region of Enrollment (participants) [Number]
United States	17 100%	5 100%	22 100%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Central Subfield Thickness, Measured Using Optical Coherence Tomography, After Treatment With CLS-TA in Subjects With Macular Edema Following Uveitis
Time Frame	2 months

Outcome Measure Data

Analysis Population Description

Intent-to-Treat set includes all randomly assigned subjects who received at least one dose of study drug.

Arm/Group Title	4 mg CLS-TA	0.8 mg CLS-TA
Arm/Group Description	Single unilateral, suprachoroidal injection of 40 mg/mL (4 mg in 100 µL) of CLS-TA 4 mg CLS-TA: 4 mg/mL CLS-TA, Clearside's formulation of TA (CLS-TA, triamcinolone acetonide injectable suspension)	Single unilateral, suprachoroidal injection of 8 mg/mL (0.8 mg in 100 µL) of CLS-TA 0.8 mg CLS-TA: 0.8 mg/mL CLS-TA, Clearside's formulation of TA (CLS-TA, triamcinolone acetonide injectable suspension)
Measure Participants	16	5
Mean (Standard Deviation) [Microns]	-164.44 (173.148)	-78.20 (121.890)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	4 mg CLS-TA
	Comments	A paired t-test was used to assess the statistical significance of the change between Baseline and Month 2. A sample size of 16 subjects would have 80% power to detect a difference of 75, assuming a standard deviation of 100, using a paired t-test with a 0.050 two-sided significance level.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0017
	Comments	The primary analysis of the primary efficacy endpoint was the comparison between the Baseline and Month 2 values for the 4 mg treatment group. No adjustments for multiplicity were necessary.
	Method	Paired t-test, two-sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-164.44
	Confidence Interval	(2-Sided) 95%; -256.7 to -72.2
	Parameter Dispersion	Type: Standard Deviation; Value: 173.148
	Estimation Comments

Adverse Events

Time Frame	8 weeks
Arm/Group Title	4 mg CLS-TA		0.8 mg CLS-TA
Arm/Group Description	Single unilateral, suprachoroidal injection of 40 mg/mL (4 mg in 100 µL) of CLS-TA 4 mg CLS-TA: 4 mg/mL CLS-TA, Clearside's formulation of TA (CLS-TA, triamcinolone acetonide injectable suspension)		Single unilateral, suprachoroidal injection of 8 mg/mL (0.8 mg in 100 µL) of CLS-TA 0.8 mg CLS-TA: 0.8 mg/mL CLS-TA, Clearside's formulation of TA (CLS-TA, triamcinolone acetonide injectable suspension)
All Cause Mortality
	4 mg CLS-TA		0.8 mg CLS-TA
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/5 (0%)
Serious Adverse Events
	4 mg CLS-TA		0.8 mg CLS-TA
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/17 (5.9%)		0/5 (0%)
Cardiac disorders
Atrial fibrillation	1/17 (5.9%)	1	0/5 (0%)	0
Other (Not Including Serious) Adverse Events
	4 mg CLS-TA		0.8 mg CLS-TA
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/17 (82.4%)		5/5 (100%)
Cardiac disorders
Palpitations	1/17 (5.9%)	1	0/5 (0%)	0
Eye disorders
Anterior chamber cell	1/17 (5.9%)	1	0/5 (0%)	0
Anterior chamber inflammation	0/17 (0%)	0	1/5 (20%)	1
Blindness transient	0/17 (0%)	0	1/5 (20%)	1
Conjunctival haemorrhage	1/17 (5.9%)	1	2/5 (40%)	2
Conjunctival haemorrhage	1/17 (5.9%)	1	0/5 (0%)	0
Conjunctival oedema	1/17 (5.9%)	1	0/5 (0%)	0
Dry eye	1/17 (5.9%)	1	0/5 (0%)	0
Dry eye	1/17 (5.9%)	1	0/5 (0%)	0
Eye pain	3/17 (17.6%)	3	0/5 (0%)	0
Foreign body sensation in eyes	1/17 (5.9%)	1	0/5 (0%)	0
Keratitis	1/17 (5.9%)	1	0/5 (0%)	0
Macular oedema	0/17 (0%)	0	3/5 (60%)	3
Macular oedema	2/17 (11.8%)	2	1/5 (20%)	1
Ocular discomfort	1/17 (5.9%)	1	0/5 (0%)	0
Punctate keratitis	1/17 (5.9%)	1	0/5 (0%)	0
Retinal artery occlusion	0/17 (0%)	0	1/5 (20%)	1
Uveitis	1/17 (5.9%)	1	1/5 (20%)	1
Uveitis	3/17 (17.6%)	3	0/5 (0%)	0
Visual acuity reduced	1/17 (5.9%)	1	0/5 (0%)	0
General disorders
Injection site pain	1/17 (5.9%)	1	1/5 (20%)	1
Papillitis	1/17 (5.9%)	1	0/5 (0%)	0
Papillitis	1/17 (5.9%)	1	0/5 (0%)	0
Infections and infestations
Bronchitis	1/17 (5.9%)	1	0/5 (0%)	0
Gastrointestinal infection	1/17 (5.9%)	1	0/5 (0%)	0
Sinusitis	1/17 (5.9%)	1	0/5 (0%)	0
Tooth infection	0/17 (0%)	0	1/5 (20%)	1
Upper respiratory tract infection	0/17 (0%)	0	1/5 (20%)	1
Injury, poisoning and procedural complications
Contusion	0/17 (0%)	0	1/5 (20%)	1
Fall	0/17 (0%)	0	1/5 (20%)	1
Investigations
Blood pressure diastolic increased	1/17 (5.9%)	1	0/5 (0%)	0
Blood pressure systolic increased	1/17 (5.9%)	1	0/5 (0%)	0
Heart rate decreased	1/17 (5.9%)	1	0/5 (0%)	0
Intraocular pressure increased	1/17 (5.9%)	1	0/5 (0%)	0
Intraocular pressure increased	1/17 (5.9%)	1	0/5 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	0/17 (0%)	0	1/5 (20%)	1
Psychiatric disorders
Substance-induced psychotic disorder	1/17 (5.9%)	2	0/5 (0%)	0
Vascular disorders
Hypertension	2/17 (11.8%)	2	0/5 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The institution and investigators participating in this trial shall have no right to publish or present the results of this study without the prior written consent of Clearside.