Date: 2016-05-04
Type of information: Interim results
phase: 1
Announcement: interim results
Company: Isarna Therapeutics (Germany)
Product: ISTH0036 - antisense oligonucleotide directed against TGF-ß2 mRNA
Action
mechanism: antisense drug/oligonucleotide. ISTH0036 is a locked nucleic acid-modified antisense oligonucleotide selectively targeting the messenger ribonucleic acid (mRNA) of TGF-?2. TGF-ß (transforming growth factor beta) plays an important role in key pathways such as cell proliferation, cell differentiation, immune response and tissue modeling. Preclinical studies have demonstrated that ISTH0036 is highly potent and shows selective target engagement (TGF-ß2 mRNA and protein downregulation) consistent with long-lasting tissue uptake and pharmacodynamic effects.
Disease: patients with advanced glaucoma undergoing filtration surgery (trabeculectomy) due to uncontrollable elevated intraocular pressure (IOP)
Therapeutic area: Ophtalmological diseases
Country: Germany
Trial
details: This study evaluates the addition of ISTH0036, an antisense oligonucleotide against TGF-?2, to glaucoma filtration surgery (trabeculectomy). The treatment aims at improving the surgery outcome by prevention of excessive scarring and trabecular meshwork transformation. (NCT02406833)
Latest
news: * On May 4, 2016, Isarna Therapeutics announced the presentation of the first clinical interim data for its lead candidate ISTH0036, a locked nucleic acid-modified antisense oligonucleotide, currently in phase I development for the treatment of advanced-stage glaucoma. The purpose of this first-in-human Phase I trial, conducted at the ophthalmology departments of the University Hospitals of Mainz, Tuebingen and Magdeburg, Germany, is to evaluate safety and tolerability and preliminary clinical efficacy of intravitreal injections of ISTH0036 in patients with advanced primary open angle glaucoma undergoing filtration surgery (trabeculectomy) with Mitomycin C due to uncontrollable elevated intraocular pressure. Glaucoma patients scheduled for filtration surgery receive a single intravitreal injection of ISTH0036 at the end of trabeculectomy in escalating total doses of 6.75 µg, 22.5 µg, 67.5 µg or 225 µg, respectively, resulting in calculated intraocular ISTH0036 concentrations in the vitreous humor of 0.3 µM, 1 µM, 3 µM or 10 µM after injection. Outcomes assessed include: type and frequency of adverse events, intraocular pressure, number of interventions post trabeculectomy, bleb survival, visual acuity and visual field, slit lamp biomicroscopy and optic disc status. The first three dose levels have been completed meanwhile and enrollment for the trial is planned to be completed in Q2/2016. Safety analyses of the 9 patients treated so far at the first 3 dose levels up to 67.5 µg revealed excellent tolerability for ISTH0036. No treatment associated adverse events, serious adverse events or dose limiting toxicities were observed. The preliminary results suggest that intravitreal injection of ISTH0036, a potent and selective antisense oligonucleotide targeting transforming growth factor beta 2 (TGF-ß2), is safe and well tolerable at therapeutic dose levels. * On April 16, 2015, Isarna Therapeutics, the leader in transforming growth factor beta (TGF-ß) targeted antisense therapeutics, announced the initiation of a Phase I clinical trial with ISTH0036, an antisense oligonucleotide selectively targeting TGF-ß2 to treat advanced glaucoma. This first-in-human Phase I trial, conducted at the University Hospitals of Mainz and Tuebingen, Germany, is designed to evaluate the safety and long-term tolerability of ISTH0036 in patients with advanced glaucoma undergoing filtration surgery (trabeculectomy) due to uncontrollable elevated intraocular pressure (IOP). The trial will enroll approximately 24 - 30 patients, who will be treated with escalating doses of ISTH0036. In addition to safety, patients will be monitored for intraocular pressure and visual field preservation.
