PMID- 36247818
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221019
IS  - 2666-9145 (Electronic)
IS  - 2666-9145 (Linking)
VI  - 1
IP  - 3
DP  - 2021 Sep
TI  - Phase 1 Study of THR-687, a Novel, Highly Potent Integrin Antagonist for the 
      Treatment of Diabetic Macular Edema.
PG  - 100040
LID - 10.1016/j.xops.2021.100040 [doi]
LID - 100040
AB  - PURPOSE: To evaluate the safety and preliminary efficacy of THR-687 in patients 
      with center-involved diabetic macular edema (DME). DESIGN: Phase 1, open-label, 
      multicenter, 3 + 3 dose-escalation study with 3-month follow-up. PARTICIPANTS: 
      Patients 18 years of age or older with visual impairment resulting from DME. 
      METHODS: Single intravitreal injection of THR-687 (0.4 mg, 1.0 mg, or 2.5 mg). 
      MAIN OUTCOME MEASURES: The primary outcome measure was the incidence of 
      dose-limiting toxicities (DLTs). The secondary outcome measure was the incidence 
      of adverse events (AEs), including the occurrence of laboratory abnormalities. 
      Exploratory outcome measures included changes from baseline in best-corrected 
      visual acuity (BCVA) and central subfield thickness (CST), assessments of 
      ischemia and leakage on fluorescein angiography, and THR-687 levels in plasma. 
      RESULTS: Twelve patients were treated: 3 patients received 0.4 mg of THR-687, 3 
      patients received 1.0 mg of THR-687, and 6 patients received 2.5 mg of THR-687. 
      Most patients were men (9/12 patients). Their mean age was 57.8 years. No DLTs or 
      serious AEs were reported at any of the dose levels tested. Overall, 9 AEs in the 
      study eye were reported for 5 of 12 patients. Of those, 4 AEs in 3 of 12 patients 
      were deemed treatment related by the investigator, all of which were mild, 
      started on the day of the injection, and had resolved within 28 days without 
      treatment. Overall, mean gains from baseline in BCVA were observed at all study 
      visits with a rapid onset (7.2 Early Treatment Diabetic Retinopathy Study [ETDRS] 
      letters at day 7) and a durability up to the end of the study (8.3 ETDRS letters 
      at month 3). A mean decrease in CST was observed up to month 1. Overall, the mean 
      BCVA gains and CST decreases were highest at the highest THR-687 dose level 
      tested. THR-687 was undetectable in plasma at 7 days after the injection. 
      CONCLUSIONS: At all dose levels tested, a single intravitreal injection of 
      THR-687 was safe and well tolerated. Preliminary efficacy was observed by a rapid 
      gain in BCVA with 3 months' durability and a decrease in CST up to 1 month after 
      the injection.
CI  - (c) 2021 by the American Academy of Ophthalmology.
FAU - Khanani, Arshad M
AU  - Khanani AM
AD  - Reno School of Medicine, University of Nevada, Reno, Nevada.
AD  - Sierra Eye Associates, Reno, Nevada.
FAU - Patel, Sunil S
AU  - Patel SS
AD  - Ophthalmology Specialists of Texas, PLLC, and Integrated Clinical Research, LLC, 
      Abilene, Texas.
FAU - Gonzalez, Victor H
AU  - Gonzalez VH
AD  - Valley Retina Institute, McAllen, Texas.
FAU - Moon, Suk J
AU  - Moon SJ
AD  - Center for Retina & Macular Disease, Haines City, Florida.
FAU - Jaffe, Glenn J
AU  - Jaffe GJ
AD  - Department of Ophthalmology, Duke University, Durham, North Carolina.
FAU - Wells, John A
AU  - Wells JA
AD  - Palmetto Retina Center, Columbia, South Carolina.
FAU - Kozma, Petra
AU  - Kozma P
AD  - Oxurion NV, Leuven, Belgium.
FAU - Dugel, Pravin U
AU  - Dugel PU
AD  - USC Roski Eye Institute, Keck School of Medicine, University of Southern 
      California, Los Angeles, California.
FAU - Maturi, Raj K
AU  - Maturi RK
AD  - Midwest Eye Institute, Indianapolis, Indiana; Department of Ophthalmology, 
      Indiana University School of Medicine, Indianapolis, Indiana.
LA  - eng
PT  - Journal Article
DEP - 20210714
PL  - Netherlands
TA  - Ophthalmol Sci
JT  - Ophthalmology science
JID - 9918230896206676
PMC - PMC9562295
OTO - NOTNLM
OT  - AE, adverse event
OT  - BCVA, best-corrected visual acuity
OT  - CI, confidence interval
OT  - CST, central subfield thickness
OT  - DLT, dose-limiting toxicity
OT  - DME
OT  - DME, diabetic macular edema
OT  - ETDRS, Early Treatment Diabetic Retinopathy Study
OT  - FA, fluorescein angiography
OT  - Integrin antagonist
OT  - Intravitreal injection
OT  - NPDR, nonproliferative diabetic retinopathy
OT  - Phase 1
OT  - RGD, arginine-glycine-aspartic acid
OT  - SD-OCT, spectral-domain OCT
OT  - THR-687
OT  - VEGF, vascular endothelial growth factor
EDAT- 2021/07/14 00:00
MHDA- 2021/07/14 00:01
PMCR- 2021/07/14
CRDT- 2022/10/17 04:57
PHST- 2021/04/01 00:00 [received]
PHST- 2021/07/01 00:00 [revised]
PHST- 2021/07/07 00:00 [accepted]
PHST- 2022/10/17 04:57 [entrez]
PHST- 2021/07/14 00:00 [pubmed]
PHST- 2021/07/14 00:01 [medline]
PHST- 2021/07/14 00:00 [pmc-release]
AID - S2666-9145(21)00038-5 [pii]
AID - 100040 [pii]
AID - 10.1016/j.xops.2021.100040 [doi]
PST - epublish
SO  - Ophthalmol Sci. 2021 Jul 14;1(3):100040. doi: 10.1016/j.xops.2021.100040. 
      eCollection 2021 Sep.