Suprachoroidal Injection of CLS-TA Alone or With Aflibercept in Subjects With Diabetic Macular Edema (HULK)

Open-Label Study of the Safety and Efficacy of Suprachoroidal CLS-TA Alone or in Combination With Intravitreal Aflibercept for the Treatment of Diabetic Macular Edema

This study is designed to demonstrate the safety and tolerability of suprachoroidal CLS-TA alone or in combination with intravitreal aflibercept in subjects with diabetic macular edema associated with diabetes mellitus.

Study Overview

• Status: Completed
• Conditions: Diabetic Macular Edema
• Intervention / Treatment: Drug: IVT Aflibercept; Drug: SC CLS-TA

Detailed Description

This is a Phase 1/2, multicenter, open-label study in subject with DME associated with diabetes mellitus.

Subjects will be screened and if eligible, will be assigned to study arm at the Baseline Visit (Visit 1, Day 0).

Following the Baseline Visit, subjects will participate in six monthly follow-up visits (Visit 2-7; Weeks 4-24) for safety and efficacy assessments and to determine whether additional therapy is needed based upon pre-defined criteria.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Mountain View, California, United States, 94040
      • Retina Vitreous Associates Medical Group Inc
  • Texas
    • The Woodlands, Texas, United States, 77384
      • Retina Consultants of Houston, PA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men or women ≥ 18 years of age with type 1 or type 2 diabetes mellitus
• DME with central involvement (>320 microns in the central subfield on SD-OCT) in the study eye
• ETDRS BCVA letter score of 83 to 14, inclusive (Snellen equivalent of 20/25 to 20/500) in the study eye

Exclusion Criteria:

• Evidence of DME due to any other cause other than diabetes mellitus in the study eye
• PRP or focal laser photocoagulation in the study eye within 90 days of screening
• Intraocular pressure ≥ 22 mmHg or uncontrolled glaucoma (open angle or angle closure) in the study eye
• History of any previous ophthalmic surgeries in the study eye within 90 days of screening
• High risk PDR in the study eye, for whom enrollment into the study, in the principal investigator's opinion would put the eye at undue risk for vision loss
• Any previous treatment in the study eye with ILUVIEN implant
• Previous treatment for DME in the study eye (TX naive arm only); treatment in the study eye for DME greater than 1 year prior to screening can be considered as treatment naive, at the investigator's discretion
• Subjects previously treated for DME cannot have been treated in the study eye with an intravitreal injection of anti-VEGF or periocular corticosteroids within 90 days prior to screening (Previous TX arm only)
• Subjects previously treated for DME cannot have been treated in the study eye with intraocular corticosteroids within 6 months prior to screening (Previous TX arm only)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TX Naïve Arm; Treatment in the TX Naive arm will consist of one unilateral injection of IVT aflibercept in combination with one unilateral injection of SC CLS-TA in the same eye.	Drug: IVT Aflibercept; IVT aflibercept [2 mg (50 µL)]; Other Names: Aflibercept; Drug: SC CLS-TA; [4 mg (100 µL)]; Other Names: Triamcinolone Acetonide
Experimental: Previous TX Arm; Treatment in the Previous TX arm of the study will consist of one unilateral injection of SC CLS-TA.	Drug: SC CLS-TA; [4 mg (100 µL)]; Other Names: Triamcinolone Acetonide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events	Number of participants with treatment emergent adverse events and serious adverse events reported over 6 months of follow-up	Over 6 months of follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in Intraocular Pressure	Baseline and change from baseline at 6 months in intraocular pressure as measured by applanation tonometry	Baseline and 6 months
Mean Change From Baseline in Central Subfield Thickness	Baseline and change from baseline at 6 months in central subfield thickness. 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.	Baseline and 6 months
Best Corrected Visual Acuity	Baseline and Change from baseline at 6 months in best corrected visual acuity before and after treatment 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 as the number of letters read correctly on an ETDRS eye chart. A positive change from baseline value represents an improvement in vision.	Baseline and 6 months
CLS-TA Injections	After the initial treatment with CLS-TA, with or without intravitreal aflibercept, at Baseline, retreatment with CLS-TA was allowed in either treatment group from Month 2 through Month 6 if pre-defined retreatment criteria were met. Number of patients receiving 0, 1, 2, 3, 4 or 5 retreatments with CLS-TA.	2 to 6 months following initial treatment with study drug

Collaborators and Investigators

• Sponsor: Clearside Biomedical, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2016
• Primary Completion (Actual): October 17, 2017
• Study Completion (Actual): October 17, 2017

Study Registration Dates

• First Submitted: October 25, 2016
• First Submitted That Met QC Criteria: October 28, 2016
• First Posted (Estimate): October 31, 2016

Study Record Updates

• Last Update Posted (Actual): May 13, 2021
• Last Update Submitted That Met QC Criteria: April 22, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Triamcinolone; Diabetes mellitus; Aflibercept; Diabetic retinopathy; Choroid; Microneedle; Triamcinolone acetonide; Microinjection; Suprachoroidal; Choroid Injection
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Macular Edema; Edema; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Triamcinolone; Triamcinolone Acetonide; Triamcinolone hexacetonide; Triamcinolone diacetate; Aflibercept
• Other Study ID Numbers: CLS1004-101

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