TY - JOUR
T1 - Suprachoroidal CLS-TA plus Intravitreal Aflibercept for Diabetic Macular Edema
T2 - A Randomized, Double-Masked, Parallel-Design, Controlled Study
AU - Barakat, Mark R.
AU - Wykoff, Charles C.
AU - Gonzalez, Victor
AU - Hu, Allen
AU - Marcus, Dennis
AU - Zavaleta, Eric
AU - Ciulla, Thomas A.
N1 - Funding Information:
Supported by Clearside Biomedical, Inc., Alpharetta, Georgia. The sponsor participated in the design of the study, conducting the study, data collection, data management, data analysis, interpretation of the data, and preparation and review of the manuscript. Disclosure(s): All authors have completed and submitted the ICMJE disclosures form. The author(s) have made the following disclosure(s): M.R.B.: Consultant - Allegro, Allergan, Alimera, Bausch & Lomb, EyePoint Pharmaceuticals, Kodiak Sciences, Genentech, Novartis, Ocular Therapeutix, RegenxBio; Financial support - Clearside Biomedical; Lecturer - Genentech, Novartis; Equity owner - NeuBase, Oxurion. C.W.: Consultant - Adverum, Alimera, Allergan, Apellis, Bayer, Chengdu Kanghong, Clearside Biomedical, Genentech, Kodiak Sciences, NGM Biopharmaceuticals, Iveric Bio, Kodiak, Novartis, Opthea, Regeneron, Recens Medical, Regenxbio, Roche, Santen, Takeda, Acucela, Aerpio, Allegro, Alnylam, Arctic Vision, Bausch and Lomb, Corcept Therapeutics, DORC, EyePoint, Gyroscope, Merck, Notal Vision, ONL Therapeutics, Oxurion, Palatin, PolyPhotonix, Thea Open Innovation; Financial support - Regeneron, Adverum, Allergan, Apellis, Chengdu Kanghong, Clearside Biomedical, Genentech, Iveric, Kodiak Sciences, NGM Biopharmaceuticals, Novartis, Opthea, Recens Medical, Regeneron, Regenxbio, Roche, Aerie Pharmaceuticals, Aldeyra, Gemini Therapeutics, Graybug Vision, IONIS Pharmaceutical, LMRI, Mylan, Neurotech Pharmaceuticals, Outlook Therapeutics, Samsung Bioepis, Senju, Taiwan Liposome Company, Xbrane BioPharma, Santen; Lecturer - Regeneron V.G.: Consultant - Genentech, Regeneron, Thrombogenics, Alcon, Allergan, Alimera, Valeant, Bausch & Lomb, Santen, Topcon, Beaver-Visitec International, and AbbVie; Financial support - Genetech, Regeneron, Thrombogenics, Alcon, Allergan, Alimera, Valeant, Santen, Iconic, Allegro, Eyegate, DRCR.net, Clearside Biomedical, Boehringer Ingelheim, Opternative, Insite Vision, Astellas, Graybug, Chengdu Kanghong, Mallinckrodt, Opthea, 60° Pharmaceuticals, Apellis, Ribomic USA, Inc.; Equity owner - Panoptica D.M.: Consultant - Regeneron, Genentech; Financial support - Allergan, Alcon, Aerpio, Kalvista, Ionis, Mylan, Samsung, Novartis, Opthea, Chengdu, Clearside Biomedical, Astellas, Allegro, Alimera, Ophthotech, Outlook, Gemini, Genentech, Thrombogenics, Tyrogenex, Graybug, Topcon, Optos, Xplore, Gyroscope, Stealth Spiam, Aerie, Apellis, Roche, Novartis, OHR, Xplore, Regenxbio, Regeneron, Kodiak, Zeiss, Regeneron Obtained funding: N/A
Publisher Copyright:
© 2020 American Academy of Ophthalmology
PY - 2021/1
Y1 - 2021/1
N2 - Purpose: This study evaluated the potential safety, efficacy, and durability advantages of investigational triamcinolone acetonide suspension (CLS-TA; Clearside Biomedical, Alpharetta, GA) administered suprachoroidally in conjunction with intravitreal aflibercept compared with aflibercept monotherapy for treatment of diabetic macular edema (DME). Design: TYBEE was a prospective, controlled, double-masked study. Patients were randomized 1:1 to CLS-TA and aflibercept (active) or aflibercept monotherapy (control), and assessed over 24 weeks. Participants: Treatment-naive DME patients with best-corrected visual acuity (BCVA) of 20 to 70 letters and central subfield retinal thickness (CST) of more than 300 μm. Methods: Patients in the active group (n = 36) received CLS-TA and aflibercept at baseline and week 12. Patients in the control group (n = 35) received aflibercept at baseline, week 4, week 8, and week 12. To mask both groups, sham suprachoroidal and intravitreal injections were utilized. All patients were eligible to receive aflibercept as needed at weeks 4, 8, 16, and 20 per prespecified criteria. Main Outcome Measure: Mean change in BCVA from baseline. Treatment differences were assessed with a 2-sided significance level of 0.10. Results: Mean BCVA changes from baseline to week 24 were not statistically different in the active and control groups (intention-to-treat [ITT] population: +11.4 letters and +13.8 letters [P = 0.288]; per protocol [PP] population: +12.3 letters and +13.5 letters [P = 0.664]; respectively). Greater improvement in CST was seen in the active versus control group (ITT population: –212.1 μm and –178.6 μm [P = 0.089]; PP population: –226.5 μm and –176.1 μm [P = 0.035]; respectively). Compared with the control group, eyes in the active group received fewer treatments (scheduled plus as-needed treatments averaging 4.6 versus 2.6, respectively). No treatment-related serious adverse events were observed. Ocular adverse events were low for both arms. Cataract events, all assessed as unrelated to treatment, and events of elevated intraocular pressure trended higher in the active group. Conclusions: CLS-TA administered suprachoroidally in conjunction with intravitreal aflibercept for treatment of DME provides simliar visual benefit at 24 weeks’ follow-up compared with aflibercept monotherapy, is well tolerated and shows modest anatomic benefit with potential to reduce treatment burden.
AB - Purpose: This study evaluated the potential safety, efficacy, and durability advantages of investigational triamcinolone acetonide suspension (CLS-TA; Clearside Biomedical, Alpharetta, GA) administered suprachoroidally in conjunction with intravitreal aflibercept compared with aflibercept monotherapy for treatment of diabetic macular edema (DME). Design: TYBEE was a prospective, controlled, double-masked study. Patients were randomized 1:1 to CLS-TA and aflibercept (active) or aflibercept monotherapy (control), and assessed over 24 weeks. Participants: Treatment-naive DME patients with best-corrected visual acuity (BCVA) of 20 to 70 letters and central subfield retinal thickness (CST) of more than 300 μm. Methods: Patients in the active group (n = 36) received CLS-TA and aflibercept at baseline and week 12. Patients in the control group (n = 35) received aflibercept at baseline, week 4, week 8, and week 12. To mask both groups, sham suprachoroidal and intravitreal injections were utilized. All patients were eligible to receive aflibercept as needed at weeks 4, 8, 16, and 20 per prespecified criteria. Main Outcome Measure: Mean change in BCVA from baseline. Treatment differences were assessed with a 2-sided significance level of 0.10. Results: Mean BCVA changes from baseline to week 24 were not statistically different in the active and control groups (intention-to-treat [ITT] population: +11.4 letters and +13.8 letters [P = 0.288]; per protocol [PP] population: +12.3 letters and +13.5 letters [P = 0.664]; respectively). Greater improvement in CST was seen in the active versus control group (ITT population: –212.1 μm and –178.6 μm [P = 0.089]; PP population: –226.5 μm and –176.1 μm [P = 0.035]; respectively). Compared with the control group, eyes in the active group received fewer treatments (scheduled plus as-needed treatments averaging 4.6 versus 2.6, respectively). No treatment-related serious adverse events were observed. Ocular adverse events were low for both arms. Cataract events, all assessed as unrelated to treatment, and events of elevated intraocular pressure trended higher in the active group. Conclusions: CLS-TA administered suprachoroidally in conjunction with intravitreal aflibercept for treatment of DME provides simliar visual benefit at 24 weeks’ follow-up compared with aflibercept monotherapy, is well tolerated and shows modest anatomic benefit with potential to reduce treatment burden.
KW - Corticosteroid
KW - Diabetic macular edema
KW - Suprachoroidal
KW - TYBEE
KW - Triamcinolone
UR - http://www.scopus.com/inward/record.url?scp=85096527674&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85096527674&partnerID=8YFLogxK
U2 - 10.1016/j.oret.2020.08.007
DO - 10.1016/j.oret.2020.08.007
M3 - Article
C2 - 32829027
AN - SCOPUS:85096527674
VL - 5
SP - 60
EP - 70
JO - Ophthalmology Retina
JF - Ophthalmology Retina
SN - 2468-6530
IS - 1
ER -