AZALEA: Suprachoroidal Injection of CLS-TA in Patients With Non-infectious Uveitis

• Sponsor: Clearside Biomedical, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03097315
• Collaborator: (none)
• Enrollment: 38
• Locations: 10
• Arm: 1
• Actual Duration (Months): 9.7
• Patients Per Site: 3.8
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This open-label study is designed to evaluate the safety of suprachoroidally administered triamcinolone acetone injectable suspension, CLS-TA, in patients with non-infectious uveitis with and without macular edema.

Condition or Disease	Intervention/Treatment	Phase
Uveitis; Uveitis, Posterior; Uveitis, Anterior; Uveitis, Intermediate; Panuveitis	Drug: 4 mg CLS-TA Suprachoriodal Injection	Phase 3

Detailed Description

This is a Phase 3, open-label multicenter study to assess the safety of 4 mg of CLS-TA administered via suprachoroidal injection in the treatment of patients diagnosed with noninfectious uveitis with and without macular edema.

Qualified patients will be enrolled and receive two suprachoroidal injections of CLS-TA administered to the study eye approximately 12 weeks apart (Visit 2 and Visit 5). Follow-up visits will be conducted monthly up to 24 weeks (Visit 8).

Study Design

• Study Type: Interventional
• Actual Enrollment: 38 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open-label Safety Study of Suprachoroidal Triamcinolone Acetonide Injectable Suspension in Patients With Non-Infectious Uveitis
• Actual Study Start Date: Apr 4, 2017
• Actual Primary Completion Date: Jan 24, 2018
• Actual Study Completion Date: Jan 24, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 4 mg CLS-TA Suprachoriodal Injection Suprachoroidal injection of 40 mg/mL (4 mg in 100 μL) of CLS-TA	Drug: 4 mg CLS-TA Suprachoriodal Injection; CLS-TA, 40 mg/mL (4 mg in 100 microliters), will be administered as a single injection at 2 timepoints; Other Names: Triamcinolone Acetonide

Outcome Measures

Primary Outcome Measures

1. Adverse Events [Baseline to 24 weeks]

   Number of patients with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). An adverse event (AE) is the development of an undesirable medical condition or the deterioration of a preexisting medical condition after or during exposure to a pharmaceutical product, whether or not considered causally related to the product. A TEAE is an AE occurring on or after the date of the first dose of study drug or worsening relative to the pre-treatment state. An SAE is an AE that fulfils one or more of the following: results in death; is immediately life-threatening; requires hospitalization nor prolongation of hospitalization; results in persistent or significant disability or incapacity; results in a congenital abnormality or birth defect; or is an important medical event that may jeopardize the subject or may require medical intervention to present one of the outcomes listed above.

Secondary Outcome Measures

1. Mean Intraocular Pressure in the Study Eye [Baseline, 24 Weeks]

   Intraocular pressure is the fluid pressure inside the eye. Tonometry is the method eye care professionals use to determine this. IOP is an important aspect in the evaluation of patients at risk of glaucoma. Tonometers in this study were calibrated to measure pressure in millimeters of mercury.

2. Number of Patients With a Grade of 0 in Anterior Chamber Cells in the Study Eye [Baseline, 24 Weeks]

   The anterior chamber is the aqueous humor-filled space inside the eye between the iris and the cornea's innermost surface, the endothelium. The grading of cellular reaction in the anterior chamber helps in the assessment of the severity of uveitis. In this study, anterior chamber cells were graded following the Standardization of Uveitis Nomenclature working group recommendations. The following scale was used to grade the cells in the field: 0 = <1, 0.5+ = 1-5, 1+ = 6-15, 2+ = 16-25, 3+ = 26-50, and 4+ = >50 cells. A lower grade represents less inflammation in the eye.

3. Number of Patients With a Grade of 0 in Anterior Chamber Flare in the Study Eye [Baseline, 24 Weeks]

   The anterior chamber is the aqueous humor-filled space inside the eye between the iris and the cornea's innermost surface, the endothelium. The grading of intraocular inflammation or flare in the anterior chamber helps in the assessment of the severity of uveitis. In this study, anterior chamber flare was graded following the Standardization of Uveitis Nomenclature working group recommendations. The following scale was used to grade the flare: 0 = none, 1+ = faint, 2+ moderate (iris and lens details clear), 3+ = marked (iris and lens details hazy), 4+ = intense (fibrin or plastic aqueous). A lower grade represents less inflammation in the eye.

4. Number of Patients With a Grade of 0 in Vitreous Haze in the Study Eye [Baseline, 24 Weeks]

   The vitreous body is that part of the eye that fills the space in the center of the eye. The primary purpose of the vitreous body is to keep the center of the eye clear so that light can get to the retina and vision can begin. Vitreous haze involves the obstruction of the back of the eye by vitreous cells and protein exudation. In this study, vitreous haze was graded following a standardized photographic scale ranging from 0 to 4. The following scale was used to grade the vitreous haze: 0 = no inflammation, +0.5 = trace inflammation, +1 = mild blurring of the retinal vessels and optic nerve, +1.5 = optic nerve head and posterior retina view obscuration greater than +1 but less than +2, +2 = moderate blurring of the optic nerve head, +3 = marked blurring of the optic nerve head, +4 = optic nerve head not visible. A lower grade represents less inflammation in the eye.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Diagnosis of active or inactive non-infectious uveitis (pan, anterior, intermediate and posterior)

• ETDRS BCVA score of ≥ 5 letters read in the study eye

Exclusion Criteria:

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

• Intraocular pressure > 22 mmHg or uncontrolled glaucoma in the study eye; patients with IOP of 22 or less in the study eye not excluded with no more than 2 IOP-lowering medications.

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

• Any topical ocular corticosteroid in the 10 days prior to baseline; intraocular or periocular corticosteroid injections in the 2 months prior to baseline; an OZURDEX implant in the 6 months prior to baseline; RETISERT or ILUVIEN implant in the 3 years prior to baseline.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Retinal Consultants of Arizona	Phoenix	Arizona	United States	85014
2	Retina-Vitreous Associates Medical Group	Beverly Hills	California	United States	90211
3	Northern California Retina Vitreous Associates Medical Group, Inc.	Mountain View	California	United States	94040
4	Retina Group of Florida	Fort Lauderdale	Florida	United States	33308
5	Marietta Eye Clinic	Marietta	Georgia	United States	30060
6	Midwest Eye Retina Practicing at Midwest Eye Institute	Indianapolis	Indiana	United States	46290
7	Ophthalmic Consultants of Boston	Boston	Massachusetts	United States	02114
8	Texas Retina Associates	Dallas	Texas	United States	75231
9	Retina Consultants of Houston	Houston	Texas	United States	77030
10	Virginia Eye Consultants	Norfolk	Virginia	United States	23502

Sponsors and Collaborators

• Clearside Biomedical, Inc.

Investigators

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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 27, 2017

More Information

Publications

• Jabs DA, Nussenblatt RB, Rosenbaum JT; Standardization of Uveitis Nomenclature (SUN) Working Group. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. Am J Ophthalmol. 2005 Sep;140(3):509-16. Review.
• Lowder C, Belfort R Jr, Lightman S, Foster CS, Robinson MR, Schiffman RM, Li XY, Cui H, Whitcup SM; Ozurdex HURON Study Group. Dexamethasone intravitreal implant for noninfectious intermediate or posterior uveitis. Arch Ophthalmol. 2011 May;129(5):545-53. doi: 10.1001/archophthalmol.2010.339. Epub 2011 Jan 10.
• Nussenblatt RB, Palestine AG, Chan CC, Roberge F. Standardization of vitreal inflammatory activity in intermediate and posterior uveitis. Ophthalmology. 1985 Apr;92(4):467-71.

• Responsible Party: Clearside Biomedical, Inc.
• ClinicalTrials.gov Identifier: NCT03097315
• Other Study ID Numbers: CLS1001-302
• First Posted: Mar 31, 2017
• Last Update Posted: Jun 23, 2021
• Last Verified: Jun 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.: Uveitis; UME; Posterior Uveitis; Anterior Uveitis; Intermediate Uveitis; Panuveitis; Non-infectious Uveitis; Triamcinolone; Choroid; Choroidal Injection; Suprachoroidal; Microneedle; Microinjection; Triamcinolone acetonide
• Additional relevant MeSH terms: Uveitis; Panuveitis; Uveitis, Posterior; Uveitis, Intermediate; Pars Planitis; Uveitis, Anterior; Triamcinolone; Triamcinolone Acetonide; Triamcinolone hexacetonide; Triamcinolone diacetate

Study Results

Participant Flow

Arm/Group Title	4 mg CLS-TA Suprachoriodal Injection
Arm/Group Description	Suprachoroidal injection of 40 mg/mL (4 mg in 100 μL) of CLS-TA 4 mg CLS-TA Suprachoriodal Injection: CLS-TA, 40 mg/mL (4 mg in 100 microliters), will be administered as a single injection at 2 timepoints
Period Title: Overall Study
STARTED	38
Intention-to-Treat Population	38
Safety Population	38
COMPLETED	37
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	4 mg CLS-TA Suprachoriodal Injection
Arm/Group Description	Suprachoroidal injection of 40 mg/mL (4 mg in 100 μL) of CLS-TA 4 mg CLS-TA Suprachoriodal Injection: CLS-TA, 40 mg/mL (4 mg in 100 microliters), will be administered as a single injection at 2 timepoints
Overall Participants	38
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	25 65.8%
>=65 years	13 34.2%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52.4 (15.8)
Sex: Female, Male (Count of Participants)
Female	25 65.8%
Male	13 34.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 13.2%
Not Hispanic or Latino	33 86.8%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	7 18.4%
White	31 81.6%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	38 100%
Type of Uveitis in the Study Eye (Count of Participants)
Anterior uveitis	12 31.6%
Intermediate uveitis	15 39.5%
Posterior uveitis	10 26.3%
Panuveitis	10 26.3%

Outcome Measures

1. Primary Outcome

Title	Adverse Events
Description	Number of patients with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). An adverse event (AE) is the development of an undesirable medical condition or the deterioration of a preexisting medical condition after or during exposure to a pharmaceutical product, whether or not considered causally related to the product. A TEAE is an AE occurring on or after the date of the first dose of study drug or worsening relative to the pre-treatment state. An SAE is an AE that fulfils one or more of the following: results in death; is immediately life-threatening; requires hospitalization nor prolongation of hospitalization; results in persistent or significant disability or incapacity; results in a congenital abnormality or birth defect; or is an important medical event that may jeopardize the subject or may require medical intervention to present one of the outcomes listed above.
Time Frame	Baseline to 24 weeks

Outcome Measure Data

Analysis Population Description

The Safety Population included all patients who entered the study and were administered at least one dose of CLS-TA

Arm/Group Title	4 mg CLS-TA Suprachoriodal Injection
Arm/Group Description	Suprachoroidal injection of 40 mg/mL (4 mg in 100 μL) of CLS-TA 4 mg CLS-TA Suprachoriodal Injection: CLS-TA, 40 mg/mL (4 mg in 100 microliters), will be administered as a single injection at 2 timepoints
Measure Participants	38
Treatment-Emergent Adverse Events	27 71.1%
Serious Adverse Events	1 2.6%

2. Secondary Outcome

Title	Mean Intraocular Pressure in the Study Eye
Description	Intraocular pressure is the fluid pressure inside the eye. Tonometry is the method eye care professionals use to determine this. IOP is an important aspect in the evaluation of patients at risk of glaucoma. Tonometers in this study were calibrated to measure pressure in millimeters of mercury.
Time Frame	Baseline, 24 Weeks

Outcome Measure Data

Analysis Population Description

The Safety Population included all patients who entered the study and were administered at least one dose of CLS-TA

Arm/Group Title	4 mg CLS-TA Suprachoriodal Injection
Arm/Group Description	Suprachoroidal injection of 40 mg/mL (4 mg in 100 μL) of CLS-TA 4 mg CLS-TA Suprachoriodal Injection: CLS-TA, 40 mg/mL (4 mg in 100 microliters), will be administered as a single injection at 2 timepoints
Measure Participants	38
Baseline	13.3 (3.57)
Week 24	15.2 (4.40)

3. Secondary Outcome

Title	Number of Patients With a Grade of 0 in Anterior Chamber Cells in the Study Eye
Description	The anterior chamber is the aqueous humor-filled space inside the eye between the iris and the cornea's innermost surface, the endothelium. The grading of cellular reaction in the anterior chamber helps in the assessment of the severity of uveitis. In this study, anterior chamber cells were graded following the Standardization of Uveitis Nomenclature working group recommendations. The following scale was used to grade the cells in the field: 0 = <1, 0.5+ = 1-5, 1+ = 6-15, 2+ = 16-25, 3+ = 26-50, and 4+ = >50 cells. A lower grade represents less inflammation in the eye.
Time Frame	Baseline, 24 Weeks

Outcome Measure Data

Analysis Population Description

The Safety Population included all patients who entered the study and were administered at least one dose of CLS-TA

Arm/Group Title	4 mg CLS-TA Suprachoriodal Injection
Arm/Group Description	Suprachoroidal injection of 40 mg/mL (4 mg in 100 μL) of CLS-TA 4 mg CLS-TA Suprachoriodal Injection: CLS-TA, 40 mg/mL (4 mg in 100 microliters), will be administered as a single injection at 2 timepoints
Measure Participants	38
Baseline	17 44.7%
Week 24	31 81.6%

4. Secondary Outcome

Title	Number of Patients With a Grade of 0 in Anterior Chamber Flare in the Study Eye
Description	The anterior chamber is the aqueous humor-filled space inside the eye between the iris and the cornea's innermost surface, the endothelium. The grading of intraocular inflammation or flare in the anterior chamber helps in the assessment of the severity of uveitis. In this study, anterior chamber flare was graded following the Standardization of Uveitis Nomenclature working group recommendations. The following scale was used to grade the flare: 0 = none, 1+ = faint, 2+ moderate (iris and lens details clear), 3+ = marked (iris and lens details hazy), 4+ = intense (fibrin or plastic aqueous). A lower grade represents less inflammation in the eye.
Time Frame	Baseline, 24 Weeks

Outcome Measure Data

Analysis Population Description

The Safety Population included all patients who entered the study and were administered at least one dose of CLS-TA

Arm/Group Title	4 mg CLS-TA Suprachoriodal Injection
Arm/Group Description	Suprachoroidal injection of 40 mg/mL (4 mg in 100 μL) of CLS-TA 4 mg CLS-TA Suprachoriodal Injection: CLS-TA, 40 mg/mL (4 mg in 100 microliters), will be administered as a single injection at 2 timepoints
Measure Participants	38
Baseline	27 71.1%
Week 24	34 89.5%

5. Secondary Outcome

Title	Number of Patients With a Grade of 0 in Vitreous Haze in the Study Eye
Description	The vitreous body is that part of the eye that fills the space in the center of the eye. The primary purpose of the vitreous body is to keep the center of the eye clear so that light can get to the retina and vision can begin. Vitreous haze involves the obstruction of the back of the eye by vitreous cells and protein exudation. In this study, vitreous haze was graded following a standardized photographic scale ranging from 0 to 4. The following scale was used to grade the vitreous haze: 0 = no inflammation, +0.5 = trace inflammation, +1 = mild blurring of the retinal vessels and optic nerve, +1.5 = optic nerve head and posterior retina view obscuration greater than +1 but less than +2, +2 = moderate blurring of the optic nerve head, +3 = marked blurring of the optic nerve head, +4 = optic nerve head not visible. A lower grade represents less inflammation in the eye.
Time Frame	Baseline, 24 Weeks

Outcome Measure Data

Analysis Population Description

The Safety Population included all patients who entered the study and were administered at least one dose of CLS-TA

Arm/Group Title	4 mg CLS-TA Suprachoriodal Injection
Arm/Group Description	Suprachoroidal injection of 40 mg/mL (4 mg in 100 μL) of CLS-TA 4 mg CLS-TA Suprachoriodal Injection: CLS-TA, 40 mg/mL (4 mg in 100 microliters), will be administered as a single injection at 2 timepoints
Measure Participants	38
Baseline	17 44.7%
Week 24	34 89.5%

Adverse Events

Time Frame	Adverse events were collected over 24 weeks of follow-up.
Adverse Event Reporting Description	Treatment-emergent adverse events were defined as any adverse event occurring on or after the first dose of study drug or worsening from the pre-dose state.
Arm/Group Title	4 mg CLS-TA Suprachoriodal Injection
Arm/Group Description	Suprachoroidal injection of 40 mg/mL (4 mg in 100 μL) of CLS-TA 4 mg CLS-TA Suprachoriodal Injection: CLS-TA, 40 mg/mL (4 mg in 100 microliters), will be administered as a single injection at 2 timepoints
All Cause Mortality
	4 mg CLS-TA Suprachoriodal Injection
	Affected / at Risk (%)	# Events
Total	0/38 (0%)
Serious Adverse Events
	4 mg CLS-TA Suprachoriodal Injection
	Affected / at Risk (%)	# Events
Total	1/38 (2.6%)
Eye disorders
Visual acuity reduced	1/38 (2.6%)	1
Other (Not Including Serious) Adverse Events
	4 mg CLS-TA Suprachoriodal Injection
	Affected / at Risk (%)	# Events
Total	24/38 (63.2%)
Eye disorders
Conjunctival haemorrhage	5/38 (13.2%)	5
Eye inflammation	2/38 (5.3%)	2
Eye inflammation	2/38 (5.3%)	2
Eye pain	3/38 (7.9%)	5
Ocular hypertension	2/38 (5.3%)	3
Visual acuity reduced	2/38 (5.3%)	2
Cataract	2/38 (5.3%)	2
Cataract nuclear	2/38 (5.3%)	2
Cystoid macular oedema	2/38 (5.3%)	2
Eye irritation	2/38 (5.3%)	2
Vision blurred	2/38 (5.3%)	2
Visual impairment	2/38 (5.3%)	2
General disorders
Injection site pain	2/38 (5.3%)	3
Injury, poisoning and procedural complications
Procedure headache	3/38 (7.9%)	4
Investigations
Intraocular pressure increased	4/38 (10.5%)	4
Intraocular pressure increased	4/38 (10.5%)	4

Limitations/Caveats

[Not Specified]

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.