June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Main results of the First-In Human single ascending dose phase I study of ISTH0036, an antisense oligonucleotide selectively targeting transforming growth factor beta 2 (TGF-β2) in glaucoma filtration surgery
Author Affiliations & Notes
  • Bogomil Voykov
    Centre for Ophthalmology, University Hospital Tuebingen, Tuebingen, Germany
  • Hagen Thieme
    Department of Ophthalmology , Otto-von-Guericke-University, Magdeburg, Germany
  • Katharina Bell
    Ophthalmology, University Medical Center Mainz, Mainz, Germany
  • Melanie Weigel
    Department of Ophthalmology , Otto-von-Guericke-University, Magdeburg, Germany
  • Guilia Renieri
    Department of Ophthalmology , Otto-von-Guericke-University, Magdeburg, Germany
  • Barbara Wilhelm
    STZ Eyetrial, University Hospital Tuebingen, Tuebingen, Germany
  • Katrin Lorenz
    Ophthalmology, University Medical Center Mainz, Mainz, Germany
  • Petra Fettes
    Isarna Therapeutics GmbH, Munich, Germany
  • Eugen Leo
    Isarna Therapeutics GmbH, Munich, Germany
  • Norbert Pfeiffer
    Ophthalmology, University Medical Center Mainz, Mainz, Germany
  • Footnotes
    Commercial Relationships   Bogomil Voykov, Isarna Therapeutics GmbH (R); Hagen Thieme, None; Katharina Bell, None; Melanie Weigel, None; Guilia Renieri, None; Barbara Wilhelm, None; Katrin Lorenz, None; Petra Fettes, Isarna Therapeutics GmbH (E); Eugen Leo, Isarna Therapeutics GmbH (E); Norbert Pfeiffer, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 5577. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      Bogomil Voykov, Hagen Thieme, Katharina Bell, Melanie Weigel, Guilia Renieri, Barbara Wilhelm, Katrin Lorenz, Petra Fettes, Eugen Leo, Norbert Pfeiffer; Main results of the First-In Human single ascending dose phase I study of ISTH0036, an antisense oligonucleotide selectively targeting transforming growth factor beta 2 (TGF-β2) in glaucoma filtration surgery. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5577.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : To study the safety and tolerability of intravitreal ISTH0036 in patients (pts) with primary open angle glaucoma (POAG) undergoing trabeculectomy (TE).

Methods : This prospective phase I trial was performed at three sites. Glaucoma patients scheduled for filtration surgery received TE with mitomycin C and a single intravitreal injection of ISTH0036 at the end of surgery in escalating total doses of 6.75 µg, 22.5 µg, 67.5 µg or 225 µg, resulting in calculated intraocular ISTH0036 concentrations in the vitreous humor of 0.3 µM, 1 µM, 3 µM or 10 µM, respectively, after injection. Outcomes assessed included: type and frequency of adverse events, intraocular pressure (IOP), number of interventions post trabeculectomy, bleb survival, visual acuity, visual field, ERG, slit lamp biomicroscopy and optic disc assessment.

Results : In total, 12 patients were treated in the 4 dose groups. Main ocular AEs observed were corneal erosion, corneal epithelium defect, or de-/increased intraocular pressure, among others. No AE was reported to be related to ISTH0036. All other safety-related analyses (e.g. ERG) did not reveal any toxicities of concern either. The mean pre-operative IOP at decision point for TE was 27.3 mmHg +/- 12.6 mmHg (SD). Mean IOP (±SD) for dose levels 1, 2, 3, and 4 were at Day 43 9.8 mmHg ± 1.0 mmHg, 11.3 mmHg ± 6.7 mmHg, 5.5 mmHg ± 3.0 mmHg and 7.5 mmHg ± 2.3 mmHg SD; and at Day 85 9.7 mmHg ± 3.3 mmHg, 14.2 mmHg ± 6.5 mmHg, 5.8 mmHg ± 1.8 mmHg and 7.8 mmHg ± 0.6 mmHg, respectively. In contrast to IOP values of dose level 1 and 2, IOP values for dose level 3 and 4 persistently remained below 10 mmHg throughout the observation period.

Conclusions : This First-in-Human trial demonstrates that intravitreal injection of ISTH0036 at the end of trabeculectomy is safe. In addition, a dose-response trend regarding postoperative IOP was observed. 67.5 µg or 225 µg single-dose ISTH0036 administration at the time of TE resulted in IOP values remaining consistently < 10 mmHg over three months. Apart from glaucoma, ISTH0036 is currently also in development for treatment of other ophthalmic diseases, such as wet and dry AMD.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×