Suprachoroidal Injection of Triamcinolone Acetonide With IVT Aflibercept in Subjects With Macular Edema Following RVO (SAPPHIRE)

SAPPHIRE: A Randomized, Masked, Controlled Trial To Study The Safety And Efficacy Of Suprachoroidal CLS-TA In Conjunction With Intravitreal Aflibercept In Subjects With Retinal Vein Occlusion

This is a Phase 3, multicenter, randomized, masked, controlled, parallel group study of 12 months duration in treatment naïve subjects with RVO.

Study Overview

• Status: Terminated
• Conditions: Macular Edema; Retinal Vein Occlusion
• Intervention / Treatment: Drug: suprachoroidal CLS-TA; Drug: IVT aflibercept; Drug: suprachoroidal sham

Detailed Description

A randomized, masked, controlled trial to study the safety and efficacy of suprachoroidal CLS-TA in conjunction with intravitreal aflibercept in subjects with retinal vein occlusion

• Study Type: Interventional
• Enrollment (Actual): 460
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Strathfield, New South Wales, Australia, 2135
      • Strathfield Retina Clinic
    • Sydney, New South Wales, Australia, 2000
      • Sydney Retina Clinic and Day Surgery
    • Sydney, New South Wales, Australia, 2000
      • Save Site Institute, University of Sydney, Sydney Eye Hospital
    • Sydney, New South Wales, Australia, 2150
      • Marsden Eye Specialists
  • Victoria
    • East Melbourne, Victoria, Australia, 3002
      • The Royal Victorian Eye and Ear Hospital
    • Melbourne, Victoria, Australia, 3150
      • Specialist Eye Group
• Austria
  • Graz, Austria
    • University of Graz-Department of Ophthalmology
  • Linz, Austria
    • Kepler University Hospital
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 3N9
      • UBC/VGH Eye Care Centre
  • Ontario
    • London, Ontario, Canada, N6A 4V2
      • St. Joseph's Health Care London, Ivey Eye Institute
    • Ottawa, Ontario, Canada, K1H 8L6
      • University of Ottawa Eye Institute
  • Quebec
    • Boisbriand, Quebec, Canada, J7H 1S6
      • Institut De L'oeil Des Laurentides
    • Montréal, Quebec, Canada, H1T 2M4
      • CIUSSS de l'Est-de-l'Ile-de-Montreal. Hospital Maisonneuve-Rosemont, Comite d'ethique de la recherche
• Denmark
  • Glostrup, Denmark
    • Rigshospitalet
  • Roskilde, Denmark
    • Dept. of Ophthalmology, Sjællands Universitetshospital, Roskilde
• Hungary
  • Budapest, Hungary, 1083
    • Semmelweis Egyetem, Szemeszeti Klinika
  • Budapest, Hungary
    • Budapest Retina Associates
  • Budapest, Hungary, 1106
    • Bajcsy-Zsilinszky Korhaz es Rendelointezet, Szemeszeti Osztaly
  • Budapest, Hungary, 1162
    • Magyar Honvedseg Egeszsegugyi Kozpont
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem Klinikai Kozpont, Szemklinika
  • Pecs, Hungary, 7621
    • Ganglion Orvosi Központ
• India
  • Gujarat
    • Ahmedabad, Gujarat, India, 380016
      • M&J Western Regional Institute of Ophthalmology
  • Maharashtra
    • Mumbai, Maharashtra, India, 400008
      • T.N. Medical College and B.Y.L. Nair Charitable Hospital
  • New Delhi
    • Delhi, New Delhi, India, 110029
      • Department of Medical Ophthalmology, Retina & Uvea
  • Tamil Nadu
    • Madurai, Tamil Nadu, India, 625020
      • Aravind Eye Hospitals & Postgraduate Institute of Ophthalmology
  • Telangana
    • Hyderabad, Telangana, India, 500034
      • Smt. Kanuri Santhamma Centre for Vitreo Retinal Diseases
  • West Bengal
    • Kolkata, West Bengal, India, 700120
      • Disha Eye Hospital Private Limited
• Israel
  • Haifa, Israel, 3104802
    • Bnai Zion Medical Center
• Italy
  • Milan, Italy, 20157
    • ASST Fatebenefratelli Sacco - P.O.L., University of Milan, Dep. of Ophthalmology
• Philippines
  • Cebu City, Philippines, 6000
    • Cebu Doctor's University Hospital
  • Makati City, Philippines, 1209
    • Peregrine Eye & Laser Institute
  • Pasig City, Philippines, 1600
    • The Medical City
• Poland
  • Bydgoszcz, Poland, 85-631
    • Oftalmika sp. z o. o.
  • Gdansk, Poland, 80-809
    • Optimum Profesorskie Centrum Okulistyki
  • Lublin, Poland, 20-079
    • Uniwersytet Medyczny w Lublinie
  • Olsztyn, Poland, 10-424
    • Centrum Diagnostyki i Mikrochirurgii Oka LENS
• Portugal
  • Braga, Portugal, 4710-243
    • Centro Clinico Academico Braga - 2CA-Braga
  • Coimbra, Portugal, 3000-075
    • Centro Hospitalar e Universitario de Coimbra, E.P.E.
  • Porto, Portugal, 4200-319
    • Centro Hospitalar de São João, E.P.E.
• Slovakia
  • Žilina, Slovakia, 01207
    • Fakultna nemocnica s poliklinikou Zilina
• Spain
  • Barcelona, Spain
    • Hospital Universitari de Bellvitge
  • Barcelona, Spain
    • Hospital General de Catalunya
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Oviedo, Spain, 33012
    • Instituto Oftalmológico Fernández-Vega
  • Pamplona, Spain, 31008
    • Clinica Universidad de Navarra
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
  • Zaragoza, Spain
    • Hospital Clinico Universitario
  • Vizcaya
    • Bilbao, Vizcaya, Spain, 48006
      • Instituto Cinico Quirurgico de Oftalmologia
• Taiwan
  • Kaohsiung, Taiwan, 81362
    • Kaohsiung Veterans General Hospital
  • Taipei, Taiwan, 112
    • Taipei Veterans General Hospital
• United Kingdom
  • Belfast, United Kingdom, BT12 6BJ
    • Queens University Royal Victoria Hospital Trust
  • Sunderland, United Kingdom
    • Sunderland Eye Infirmary
• United States
  • Arizona
    • Peoria, Arizona, United States, 85381
      • Associated Retina Consultants, Ltd.
    • Phoenix, Arizona, United States, 85021
      • Arizona Retina and Vitreous Consultants
    • Phoenix, Arizona, United States, 85014-2709
      • Retinal Consultants of Arizona and Retinal Research Institute
    • Phoenix, Arizona, United States, 85381
      • Associated Retina Consultants, Ltd.
    • Tucson, Arizona, United States, 85704
      • Retina Centers P.C.
  • California
    • Bakersfield, California, United States, 93309
      • California Retina Research Consultants
    • Beverly Hills, California, United States, 90211-1841
      • Retina Vitreous Medical Group Clinical Research
    • Huntington Beach, California, United States, 92647
      • Atlantis Eyecare
    • La Jolla, California, United States, 92093
      • Jacobs Retina Center at the Shiley Eye Institute, UCSD
    • Mountain View, California, United States, 94040
      • Northern California Retina Vitreous Associates
    • Oakland, California, United States, 95409
      • East Bay Retina Consultants Inc.
    • Palm Desert, California, United States, 92211
      • Southern California Desert Retina Consultants
    • Palm Desert, California, United States, 92260
      • Retina Institute of California
    • Poway, California, United States, 92064-2526
      • Retina Consultants San Diego
    • Santa Ana, California, United States, 92705
      • Orange County Retina Medical Group
    • Santa Barbara, California, United States, 93103
      • California Retina Consultants CRC
    • Walnut Creek, California, United States, 94599
      • Bay Area Retina Associates
  • Colorado
    • Golden, Colorado, United States, 80401
      • Colorado Retina Associates
  • Connecticut
    • Hamden, Connecticut, United States, 06518
      • New England Retina Associates
  • Florida
    • Miami, Florida, United States, 33143-5188
      • MedEye Associates
    • Pensacola, Florida, United States, 32503
      • Retina Specialty Institute
    • Saint Petersburg, Florida, United States, 33711
      • Retina Vitreous Associates of Florida
    • Sarasota, Florida, United States, 34239
      • Sarasota Retina Institute
    • Winter Haven, Florida, United States, 33880
      • Center for Retina and Macular Disease
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory Eye Center
    • Augusta, Georgia, United States, 30909
      • Southeast Retina Center, PC
    • Marietta, Georgia, United States, 30060
      • Marietta Eye Clinic
  • Hawaii
    • 'Aiea, Hawaii, United States, 96701
      • Retina Consultants of Hawaii
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Illinois Eye and Ear Infirmary, UIC
    • Chicago, Illinois, United States, 60657
      • Illinois Retina Associates
    • Urbana, Illinois, United States, 61801
      • Carle Foundation Hospital
  • Indiana
    • Indianapolis, Indiana, United States, 46290
      • Midwest Eye Institute
  • Kansas
    • Shawnee Mission, Kansas, United States, 66204
      • Retina Associates, PA
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • Retina and Vitrous Associates of Kentucky
  • Maryland
    • Baltimore, Maryland, United States, 21287-0005
      • Wilmer Eye Institute John Hopkins University
    • Hagerstown, Maryland, United States, 21740-5940
      • Cumberland Valley Retina Consultants
  • Missouri
    • Saint Louis, Missouri, United States, 63128
      • The Retina Institute
  • New Jersey
    • Teaneck, New Jersey, United States, 07666
      • Retina Associates of NJ
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Western Carolina Retinal Associates, PA
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Cincinnati Eye Institute
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation/Cole Eye Institute
  • Oregon
    • Medford, Oregon, United States, 97504
      • Oregon Retina Institute
    • Portland, Oregon, United States, 97239
      • Casey Eye Institute/Oregon Health & Science University
  • Pennsylvania
    • Kingston, Pennsylvania, United States, 18704
      • Eye Care Specialists
    • Philadelphia, Pennsylvania, United States, 19107
      • Wills Eye Hospital
  • South Dakota
    • Rapid City, South Dakota, United States, 57701-7374
      • Black Hills Regional Eye Institute
  • Texas
    • Abilene, Texas, United States, 79606-1224
      • Retina Research Institute of Texas
    • Arlington, Texas, United States, 76012-2505
      • Texas Retina Associates-Arlington
    • Austin, Texas, United States, 78705
      • Austin Retina Associates
    • Dallas, Texas, United States, 75231
      • Texas Retina Associates
    • Houston, Texas, United States, 77030
      • Retina Consultants of Houston
    • McAllen, Texas, United States, 78503
      • Valley Retina Institute
    • San Antonio, Texas, United States, 78240-1502
      • Medical Center Ophthalmology Associates
    • The Woodlands, Texas, United States, 77384
      • Retina Consultants of Houston
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah HSC - John A. Moran Eye Center
  • Virginia
    • Richmond, Virginia, United States, 23235
      • Retina Institute of Virginia
    • Warrenton, Virginia, United States, 20186
      • Virginia Retina Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • University of Wisconsin-Madison

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:

• Has a clinical diagnosis of RVO in the study eye
• Has a CST of ≥ 300 µm in the study eye
• Has an ETDRS BCVA score of ≥ 20 letters read and ≤ 70 letters read in the study eye;
• Is naïve to local pharmacologic treatment for RVO in the study eye;

Exclusion Criteria:

• Any active ocular disease or infection in the study eye other than RVO
• History of glaucoma, intraocular pressure > 21 mmHg or ocular hypertension requiring more than one medication
• Any uncontrolled systemic disease that, in the opinion of the Investigator, would preclude participation in the study
• Any evidence of neovascularization in the study eye

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Active; IVT aflibercept (2 mg/0.05 mL) + CLS-TA (4 mg/100 µL) SC injections	Drug: suprachoroidal CLS-TA; suprachoroidal injection of CLS-TA; Other Names: Triamcinolone acetonide; Drug: IVT aflibercept; 2 mg intravitreal injection of aflibercept; Other Names: Aflibercept
ACTIVE_COMPARATOR: Control; IVT aflibercept (2 mg/0.05 mL) + sham SC procedure	Drug: IVT aflibercept; 2 mg intravitreal injection of aflibercept; Other Names: Aflibercept; Drug: suprachoroidal sham; suprachoroidal sham procedure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Subjects Demonstrating ≥ 15 Letter Improvement From Baseline in Early Treatment of Diabetic Retinopathy Study (ETDRS)	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 an ETDRS eye chart. An increase from the pre-treatment state in BCVA of 15 letters or more represents a clinically meaningful improvement.	2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in Best Corrected Visual Acuity	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 an ETDRS eye chart. A positive change from baseline value represents an improvement in vision.	6 months
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.	6 months

Collaborators and Investigators

• Sponsor: Clearside Biomedical, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 31, 2017
• Primary Completion (ACTUAL): December 10, 2018
• Study Completion (ACTUAL): December 10, 2018

Study Registration Dates

• First Submitted: November 30, 2016
• First Submitted That Met QC Criteria: November 30, 2016
• First Posted (ESTIMATE): December 2, 2016

Study Record Updates

• Last Update Posted (ACTUAL): April 14, 2021
• Last Update Submitted That Met QC Criteria: March 18, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: OCT; Eylea; Aflibercept; Optical Coherence Tomography; Anti-VEGF; RVO; Cystoid Macular Edema; ME; Subretinal Fluid; Triamcinolone acetonide; Suprachoroidal; Central Subfield Thickness
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Retinal Degeneration; Retinal Diseases; Embolism and Thrombosis; Venous Thrombosis; Thrombosis; Macular Degeneration; Macular Edema; Retinal Vein Occlusion; 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: CLS1003-301

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