June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
A Phase 1/ Phase 2 Study Evaluating the Safety and Efficacy of TTHX1114 on the Regeneration of Corneal Endothelial Cells in Patients with Corneal Endothelial Dystrophy
Author Affiliations & Notes
  • David Eveleth
    Trefoil Therapeutics, Inc, California, United States
  • Thomas Tremblay
    Trefoil Therapeutics, Inc, California, United States
  • Footnotes
    Commercial Relationships   David Eveleth Trefoil Therapeutics, Inc, Code E (Employment), Trefoil Therapeutics, Inc, Code P (Patent), Trefoil Therapeutics, Inc., Code S (non-remunerative); Thomas Tremblay Trefoil Therapeutics, Inc., Code E (Employment)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 2757 – A0246. doi:
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    • Get Citation

      David Eveleth, Thomas Tremblay; A Phase 1/ Phase 2 Study Evaluating the Safety and Efficacy of TTHX1114 on the Regeneration of Corneal Endothelial Cells in Patients with Corneal Endothelial Dystrophy. Invest. Ophthalmol. Vis. Sci. 2022;63(7):2757 – A0246.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : To assess the safety and tolerability of TTHX1114.

Methods : Protocol was reviewed/ approved by the IRB and informed consent obtained from all subjects. TTHX1114 was administered as a weekly 10mcL IC injection at doses of 1ng, 3ng, or 10ng or vehicle x 4 weeks. The study included patients with Fuchs endothelial corneal dystrophy (FECD), central endothelial cell (CEC) density < 2000 mm^2 in the study eye; adequate function in the fellow eye; and no other co-morbid conditions that would interfere with the assessment of safety or efficacy. 22 subjects were enrolled/randomized; 17 subjects received TTHX1114 (1ng [7], 3ng [3], or 10ng [7]) and 5 received placebo. Assessments included specular microscopy, slit-lamp examination, BCVA, central corneal thickness (CCT), and IOP.

Results : Of the subjects enrolled, 19/22 (86.4%) were female, 100% were White, with a mean age of 74.5. All subjects received all injections and completed the study. There did not appear to be any meaningful changes in slit-lamp, BCVA, CCT, or IOP. A total of 88 10mcL injections were administered and the mean and median change from pre-injection IOP was -1.9 and -2, respectively; the highest increase was 4mmHg. There were no deaths, SAEs, or DLTs. No AEs were considered related to TTHX1114 by the Investigator, but 4 AEs were considered related to the IC injections procedure; these events were all mild, reported only in 1 subject each, and included conjunctival hemorrhage, eye irritation, foreign body sensation in eye, and photophobia. Analysis of specular microscopy is ongoing.

Conclusions : Standard ocular assessments were sufficient to assess the safety and tolerability of TTHX1114 and an injection volume of 10mcL which appeared to be safe and well-tolerated. The MTD was not exceeded and the RP2D was determined to be 10ng/10mcL delivered by IC injection. The study was originally designed to also obtain a preliminary estimate of efficacy by assessment of CEC densities but this was confounded by the presence of guttae and the inability to reproducibly image the same geographic location at subsequent visits. Further dose/volume escalation should be conducted and exploration of relevant efficacy endpoints which may include eligibility criteria requiring significantly abnormal baseline measurements and/or more reliably imageable patients in additional studies.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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