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CompletedNCT02595398PEACHTREEUpdated May 28, 2021Results posted

Suprachoroidal Injection of CLS-TA in Subjects With Macular Edema Associated With Non-infectious Uveitis

A Phase 3 interventional study of 4mg CLS-TA Suprachoriodal Injection and Sham Procedure in Uveitis, Uveitis, Posterior and Uveitis, Anterior, sponsored by Clearside Biomedical, Inc.. Completed at 64 sites in 3 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-05-28.

Sponsored by Clearside Biomedical, Inc. · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
160
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

The study is designed to evaluate the safety and efficacy of suprachoroidally administered triamcinolone acetonide, CLS-TA, in subjects with macular edema associated with non-infectious uveitis.

Read the detailed description

This is a Phase 3, randomized, masked, sham-controlled, multicenter study to assess the safety and efficacy of 4 mg of CLS-TA administered via suprachoroidal injection compared to a sham injection procedure in the treatment of subjects with macular edema associated with non-infectious uveitis.

Qualified subjects will be randomized to receive two suprachoroidal injections of CLS-TA administered to the study eye or two sham injection procedures 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).

02

Conditions studied

  • Uveitis
  • Uveitis, Posterior
  • Uveitis, Anterior
  • Uveitis, Intermediate
  • Panuveitis

Keywords

  • Uveitis
  • UME
  • Posterior Uveitis
  • Anterior Uveitis
  • Intermediate Uveitis
  • Panuveitis
  • Non-infectious Uveitis
  • Triamcinolone
  • Choroid
  • Choroidal Injection
  • Suprachoroidal
  • Microneedle
  • Microinjection
  • Triamcinolone acetonide
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Diagnosis of non-infectious uveitis (pan, anterior, intermediate and posterior)
  • Diagnosis of macular edema associated with non-infectious uveitis (retinal thickness ≥ 300 microns)
  • Visual Acuity score of ≥ 5 letters read (20/800 Snellen equivalent) and ≤ 70 letters read (20/40 Snellen equivalent), in the study eye

Exclusion criteria

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; subjects are not excluded if IOP ≤ 22 mmHg 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.
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
160 participants (actual)

Study arms

  • Experimental
    4mg CLS-TA Suprachoriodal Injection

    Suprachoroidal injection of 40 mg/mL (4 mg in 100 µL) of CLS-TA

    Drug: 4mg CLS-TA Suprachoriodal Injection

  • Sham comparator
    Sham Procedure

    Matching suprachoroidal syringe with sham procedure

    Drug: Sham Procedure

Interventions

  • Drug4mg CLS-TA Suprachoriodal Injection

    CLS-TA, 40 mg/mL (4 mg in 100 µL), administered as a single injection at 2 timepoints

    Also known as: Triamcinolone Acetonide

  • DrugSham Procedure

    Sham procedure administered at 2 timepoints

    Also known as: suprachoroidal sham

05

What researchers measure

Primary outcomes

  1. Number of Subjects Demonstrating ≥ 15 Letter Improvement From Baseline in Best Corrected Visual Acuity at 24 Weeks

    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 electronic Visual Acuity (eVA). An increase from the pre-treatment state in BCVA of 15 letters or more represents a clinically meaningful improvement.

    Time frame: Baseline, 24 weeks

Secondary outcomes

  1. Mean Change From Baseline 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. Only images that were gradable by the central reading center were included in the analysis.

    Time frame: Baseline, 24 weeks

  2. Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

    Number of subjects with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) reported between the first dose of study drug and study exit.

    Time frame: Baseline to 24 weeks

06

Results

Posted Apr 28, 2021

Participant flow

Participant flow — Overall Study
Milestone4mg CLS-TA Suprachoriodal InjectionSham Procedure
Started9664
Intention-to-treat (itt) population9664
Safety population9664
Completed9263
Not completed41
Withdrew: Non-compliance10
Withdrew: Withdrawal by subject21
Withdrew: Lost to follow-up10

Outcome measures

PrimaryNumber of Subjects Demonstrating ≥ 15 Letter Improvement From Baseline in Best Corrected Visual Acuity at 24 Weeks

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 electronic Visual Acuity (eVA). An increase from the pre-treatment state in BCVA of 15 letters or more represents a clinically meaningful improvement.

Time frame:
Baseline, 24 weeks
Reported as:
Count of participants · Participants
Number of Subjects Demonstrating ≥ 15 Letter Improvement From Baseline in Best Corrected Visual Acuity at 24 Weeks
Participants4mg CLS-TA Suprachoriodal InjectionSham Procedure
Number of Subjects Demonstrating ≥ 15 Letter Improvement From Baseline in Best Corrected Visual Acuity at 24 Weeks4510
Statistical analysis
  • 4mg CLS-TA Suprachoriodal Injection vs Sham Procedure · Cochran-Mantel-Haenszel · p = <0.001 (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 country strata.) · Difference in percentages: 31.25 · 95% CI 15.5 to 45.9Estimated 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.
SecondaryMean Change From Baseline 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. Only images that were gradable by the central reading center were included in the analysis.

Time frame:
Baseline, 24 weeks
Reported as:
Mean · microns
Mean Change From Baseline in Central Subfield Thickness
microns4mg CLS-TA Suprachoriodal InjectionSham Procedure
Mean Change From Baseline in Central Subfield Thickness-152.6 ± 159.14-17.9 ± 150.98
SecondaryNumber of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Number of subjects with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) reported between the first dose of study drug and study exit.

Time frame:
Baseline to 24 weeks
Reported as:
Count of participants · Participants
Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Participants4mg CLS-TA Suprachoriodal InjectionSham Procedure
Experiencing at least one TEAE6745
Experiencing at least one SAE30

Adverse events

Collected over Adverse events were collected over 24 weeks of follow-up.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
4mg CLS-TA Suprachoriodal Injection0/96 (0%)3/96 (3.1%)42/96 (43.8%)
Sham Procedure0/64 (0%)0/64 (0%)29/64 (45.3%)
Most frequent serious events
Most frequent serious events
Event4mg CLS-TA Suprachoriodal InjectionSham Procedure
SialoadenitisInfections and infestations1/960/64
Lumbar vertebral fractureInjury, poisoning and procedural complications1/960/64
Retinal detachmentEye disorders1/960/64
Most frequent other events
Most frequent other events
Event4mg CLS-TA Suprachoriodal InjectionSham Procedure
Intraocular pressure increasedInvestigations17/964/64
Eye painEye disorders14/960/64
Cystoid macular oedemaEye disorders0/969/64
Ocular hypertensionEye disorders2/965/64
Cataract subcapsularEye disorders7/963/64
UveitisEye disorders2/964/64
Intraocular pressure increasedInvestigations6/962/64
HeadacheNervous system disorders5/962/64

Baseline characteristics

The Intent-to-treat population included all randomized subjects who received at least one study treatment.

Age, Categorical
Age, Categorical(Participants)4mg CLS-TA Suprachoriodal InjectionSham ProcedureTotal
<=18 years101
Between 18 and 65 years7952131
>=65 years161228
Age, Continuous
Age, Continuous(years)4mg CLS-TA Suprachoriodal InjectionSham ProcedureTotal
Mean50.40 ± 14.18050.00 ± 15.08350.24 ± 14.502
Sex: Female, Male
Sex: Female, Male(Participants)4mg CLS-TA Suprachoriodal InjectionSham ProcedureTotal
Female543488
Male423072
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)4mg CLS-TA Suprachoriodal InjectionSham ProcedureTotal
Hispanic or Latino10616
Not Hispanic or Latino8658144
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)4mg CLS-TA Suprachoriodal InjectionSham ProcedureTotal
American Indian or Alaska Native000
Asian442872
Native Hawaiian or Other Pacific Islander000
Black or African American111122
White402565
More than one race101
Unknown or Not Reported000
Region of Enrollment
Region of Enrollment(participants)4mg CLS-TA Suprachoriodal InjectionSham ProcedureTotal
United States463480
Israel7310
India432770
Type of Uveitis
Type of Uveitis(Participants)4mg CLS-TA Suprachoriodal InjectionSham ProcedureTotal
Anterior uveitis271441
Intermediate uveitis342357
Posterior uveitis221335
Panuveitis282452
07

Study locations

64 sites
  • Retinal Consultants of Arizona
    Phoenix, Arizona 85014, United States
  • Retina Centers, PC
    Tucson, Arizona 85704, United States
  • California Retina Consultants
    Bakersfield, California 93309, United States
  • Retina-Vitreous Associates Medical Group
    Beverly Hills, California 90211, United States
  • USC Eye Institute
    Los Angeles, California 90033, United States
  • Northern California Retina Vitreous Associates Medical Group, Inc.
    Mountain View, California 94040, United States
  • Orange County Retina Medical Group
    Santa Ana, California 92705, United States
  • University of Colorado
    Aurora, Colorado 80045, United States
  • Colorado Retina Associates
    Golden, Colorado 80401, United States
  • Retina Group of Florida
    Fort Lauderdale, Florida 33308, United States
  • Center for Retina and Macular Disease
    Lakeland, Florida 33805, United States
  • Emory Eye Center Emory University
    Atlanta, Georgia 30322, United States
  • Marietta Eye Clinic
    Marietta, Georgia 30060, United States
  • Northwestern University
    Chicago, Illinois 60611, United States
  • University of Illinois at Chicago
    Chicago, Illinois 60612, United States
  • Illinois Retina Associates, S.C.
    Oak Park, Illinois 60304, United States
  • Midwest Eye Retina Practicing at Midwest Eye Institute
    Indianapolis, Indiana 46290, United States
  • Elman Retina Group, PA
    Baltimore, Maryland 21237, United States
  • The Retina Group of Washington
    Chevy Chase, Maryland 20815, United States
  • Valley Eye Physicians and Surgeons, PC
    Ayer, Massachusetts 01432, United States
  • Ophthalmic Consultants of Boston
    Boston, Massachusetts 02114, United States
  • Ocular Immunology and Uveitis Foundation; Massachusetts Eye Research and Surgery Institution
    Waltham, Massachusetts 01741, United States
  • Discover Vision Centers
    Independence, Missouri 64055, United States
  • Metropolitan Eye Research & Surgery Institute
    Palisades Park, New Jersey 07650, United States
  • Weill Cornell Medical College
    New York, New York 10021, United States
  • Retina Consultants PLLC
    Slingerlands, New York 12159, United States
  • Charlotte Eye Ear Nose and Throat Associates, PA
    Belmont, North Carolina 28012, United States
  • Wake Forest Baptist Health Eye Center
    Winston-Salem, North Carolina 27103, United States
  • Bergstrom Eye Research
    Fargo, North Dakota 58103, United States
  • Oregon Health & Science University Casey Eye Institute
    Portland, Oregon 97239, United States
  • Mid Atlantic Retina
    Philadelphia, Pennsylvania 19107, United States
  • University of Pittsburgh Medical Center Eye Center
    Pittsburgh, Pennsylvania 15213, United States
  • Innovative Clinical Research
    Greenville, South Carolina 29605, United States
  • Austin Retina Associates
    Austin, Texas 78705, United States
  • Texas Retina Associates
    Dallas, Texas 75231, United States
  • Retina Consultants of Houston
    Houston, Texas 77030, United States
  • Foresight Studies, LLC
    San Antonio, Texas 78233, United States
  • Retina Consultants of Houston
    The Woodlands, Texas 77384, United States
  • Virginia Eye Consultants
    Norfolk, Virginia 23502, United States
  • Vitreoretinal Associates of Washington
    Bellevue, Washington 98004, United States
  • L V Prasad Eye Hospital
    Hyderabad, Andhra Pradesh, India
  • Sri Sankaradeva Nethralaya
    Guwahati, Assam, India
  • M&J Western Regional Institute of Ophthalmology
    Ahmedabad, Gujarat, India
  • JSS Hospital
    Mysore, Karnataka, India
  • Regional Institute of Ophthalmology
    Thiruvananthapuram, Kerala, India
  • TN Medical College and BYL Nair Hospital
    Mumbai, Maharashtra, India
  • PBMA's H V Desai Eye Hospital
    Pune, Maharashtra, India
  • Sankara Nethralaya
    Chennai, Tamil Nadu, India
  • Sankara Eye Hospital
    Coimbatore, Tamil Nadu, India
  • King George's Medical University
    Lucknow, Uttar Pradesh, India
  • Sanjay Gandhi Postgraduate Institute of Medical Sciences
    Lucknow, Uttar Pradesh, India
  • Icare Eye Hospital & PG Institute
    Noida, Uttar Pradesh, India
  • Calcutta Medical Research Institute
    Kolkata, 700027, India
  • Disha Eye Hospital
    Kolkata, India
  • Dr Rajendra Prasad Centre for Ophthalmic Sciences
    New Delhi, 110029, India
  • Dr. Shroff's Charity Eye Hospital
    New Delhi, India
  • Soroka Medical Center
    Beer Sheva, 85025, Israel
  • Bnai Zion Medical Center
    Haifa, 3104802, Israel
  • Rambam Health Corp
    Haifa, 3109601, Israel
  • Hadassah-Hebrew University Medical Center
    Jerusalem, 91120, Israel
  • Rabin Medical Center
    Petah Tikva, 4941492, Israel
  • Sheba Medical Center
    Ramat Gan, 52621, Israel
  • Kaplan Medical Center
    Rehovot, 76100, Israel
  • Tel-Aviv Sourasky Medical Center
    Tel Aviv, 64239, Israel
08

References and documents

Publications

  • 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. 2023 Feb;12(1):577-591. doi: 10.1007/s40123-022-00603-x. Epub 2022 Nov 18. PubMed 36399237 ↗
  • Bhattacharyya S, Hariprasad SM, Albini TA, Dutta SK, John D, Padula WV, Harrison D, Joseph G. Suprachoroidal Injection of Triamcinolone Acetonide Injectable Suspension for the Treatment of Macular Edema Associated With Uveitis in the United States: A Cost-Effectiveness Analysis. Value Health. 2022 Oct;25(10):1705-1716. doi: 10.1016/j.jval.2022.07.008. Epub 2022 Aug 31. PubMed 36055922 ↗
  • Singer MA, Merrill P, Yeh S, Hall C, Kapik B, Ciulla TA. Suprachoroidal triamcinolone acetonide versus rescue therapies for the treatment of uveitic macular oedema: A post hoc analysis of PEACHTREE. Clin Exp Ophthalmol. 2022 Jan;50(1):23-30. doi: 10.1111/ceo.14024. Epub 2021 Dec 27. PubMed 34741564 ↗
  • Price KW, Albini TA, Yeh S. Suprachoroidal Injection of Triamcinolone- Review of a Novel Treatment for Macular Edema Caused by Noninfectious Uveitis. US Ophthalmic Rev. 2020 Fall;13(2):76-79. doi: 10.17925/usor.2020.13.2.76. Epub 2020 Dec 23. PubMed 34322164 ↗

Study documents

  • Protocol and statistical analysis plan · Apr 12, 2017

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT02595398
Lead sponsor
Clearside Biomedical, Inc.
Responsible party
Sponsor
First posted
Nov 3, 2015
Start date
Nov 17, 2015
Primary completion
Jan 18, 2018
Completion
Jan 18, 2018
Results posted
Apr 28, 2021
Last update
May 28, 2021

Study contacts

Thomas Cuilla, MD, MBA
study director · Clearside Biomedical, Inc.

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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