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

Open-label Safety Study of Suprachoroidal Triamcinolone Acetonide Injectable Suspension in Patients With Non-Infectious Uveitis

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.

Study Overview

• Status: Completed
• Conditions: Uveitis, Anterior; Panuveitis; Uveitis; Uveitis, Posterior; Uveitis, Intermediate
• Intervention / Treatment: Drug: 4 mg CLS-TA Suprachoriodal Injection

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 Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85014
      • Retinal Consultants of Arizona
  • California
    • Beverly Hills, California, United States, 90211
      • Retina-Vitreous Associates Medical Group
    • Mountain View, California, United States, 94040
      • Northern California Retina Vitreous Associates Medical Group, Inc.
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Retina Group of Florida
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Marietta Eye Clinic
  • Indiana
    • Indianapolis, Indiana, United States, 46290
      • Midwest Eye Retina Practicing at Midwest Eye Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Ophthalmic Consultants of Boston
  • Texas
    • Dallas, Texas, United States, 75231
      • Texas Retina Associates
    • Houston, Texas, United States, 77030
      • Retina Consultants of Houston
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Virginia Eye Consultants

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	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.	Baseline to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Intraocular Pressure in the Study Eye	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.	Baseline, 24 Weeks
Number of Patients With a Grade of 0 in Anterior Chamber Cells in the Study Eye	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.	Baseline, 24 Weeks
Number of Patients With a Grade of 0 in Anterior Chamber Flare in the Study Eye	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.	Baseline, 24 Weeks
Number of Patients With a Grade of 0 in Vitreous Haze in the Study Eye	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.	Baseline, 24 Weeks

Collaborators and Investigators

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

Publications and helpful links

General 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. doi: 10.1016/j.ajo.2005.03.057.
• 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. doi: 10.1016/s0161-6420(85)34001-0.
• 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.
• Yeh S, Henry CR, Kapik B, Ciulla TA. Triamcinolone Acetonide Suprachoroidal Injectable Suspension for Uveitic Macular Edema: Integrated Analysis of Two Phase 3 Studies. Ophthalmol Ther. 2022 Nov 18. doi: 10.1007/s40123-022-00603-x. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): April 4, 2017
• Primary Completion (Actual): January 24, 2018
• Study Completion (Actual): January 24, 2018

Study Registration Dates

• First Submitted: March 27, 2017
• First Submitted That Met QC Criteria: March 27, 2017
• First Posted (Actual): March 31, 2017

Study Record Updates

• Last Update Posted (Actual): June 23, 2021
• Last Update Submitted That Met QC Criteria: June 18, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Triamcinolone; Uveitis; Choroid; Microneedle; Intermediate Uveitis; Triamcinolone acetonide; Panuveitis; Non-infectious Uveitis; Posterior Uveitis; Microinjection; Suprachoroidal; UME; Anterior Uveitis; Choroidal Injection
• Additional Relevant MeSH Terms: Eye Diseases; Uveal Diseases; Choroid Diseases; Choroiditis; Uveitis; Uveitis, Posterior; Panuveitis; Uveitis, Intermediate; Pars Planitis; Uveitis, Anterior; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Immunosuppressive Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Triamcinolone; Triamcinolone Acetonide; Triamcinolone hexacetonide; Triamcinolone diacetate
• Other Study ID Numbers: CLS1001-302

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No