Abstract
Purpose :
To study the safety and tolerability and preliminary clinical efficacy of intravitreal ISTH0036 in patients with primary open angle glaucoma (POAG) undergoing trabeculectomy with mitomycin C.
Methods :
This prospective Phase I trial is performed at three sites. Glaucoma patients scheduled for filtration surgery receive intravitreal injections 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 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 (IOP), number of interventions post trabeculectomy, bleb survival, visual acuity and visual field, slit lamp biomicroscopy and optic disc status.
Results :
In this ongoing study so far six patients have been treated (dose level 1 and – ongoing - dose level 2). For dose level 1 good safety and tolerability was confirmed. No treatment associated adverse events or dose limiting toxicities were observed. The mean pre-operative IOP of patients at dose level 1 was 34.7 mmHg and post-operative 9.8 mmHg at the 6 week follow up and 9.7 mmHg at the 12 week follow up (SD: 13.35, 0.82, and 2.66, respectively). Updated results of this ongoing trial will be presented at the meeting.
Conclusions :
Preliminary results of this First-in-Human trial suggest that intravitreal injection at the end of trabeculectomy of ISTH0036, a potent and selective antisense oligonucleotide targeting transforming growth factor beta 2 (TGF-β2) ISTH0036 is safe and well tolerable.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.