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Your search keyword '"Katja Wosikowski"' showing total 2 results
Start Over Author "Katja Wosikowski" Publisher public library of science (plos)
2 results on '"Katja Wosikowski"'

1. First-in-human phase I study of ISTH0036, an antisense oligonucleotide selectively targeting transforming growth factor beta 2 (TGF-β2), in subjects with open-angle glaucoma undergoing glaucoma filtration surgery.

Author

Norbert Pfeiffer, Bogomil Voykov, Giulia Renieri, Katharina Bell, Paul Richter, Melanie Weigel, Hagen Thieme, Barbara Wilhelm, Katrin Lorenz, Martin Feindor, Katja Wosikowski, Michel Janicot, Daniela Päckert, Regina Römmich, Carola Mala, Petra Fettes, and Eugen Leo

Subjects
Medicine, Science
Abstract

To evaluate the safety and tolerability of intravitreal ISTH0036, an antisense oligonucleotide selectively targeting transforming growth factor beta 2 (TGF-β2), in patients with primary open angle glaucoma (POAG) undergoing trabeculectomy (TE; glaucoma filtration surgery).In this prospective phase I trial glaucoma patients scheduled for TE with mitomycin C (MMC) received 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 approximately 0.3 μM, 1 μM, 3 μM or 10 μM after injection, respectively. Outcomes assessed included: type and frequency of adverse events (AEs), intraocular pressure (IOP), numbers of interventions post trabeculectomy, bleb survival, visual acuity, visual field, electroretinogram (ERG), slit lamp biomicroscopy and optic disc assessment.In total, 12 patients were treated in the 4 dose groups. Main ocular AEs observed were corneal erosion, corneal epithelium defect, or too high or too low IOP, among others. No AE was reported to be related to ISTH0036. All other safety-related analyses did not reveal any toxicities of concern, either. The mean medicated preoperative IOP at decision time-point for surgery 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 for dose levels 1 and 2, IOP values for dose levels 3 and 4 persistently remained below 10 mmHg throughout the observation period.This first-in-human trial demonstrates that intravitreal injection of ISTH0036 at the end of TE is safe. Regarding IOP control, single-dose ISTH0036 administration of 67.5 μg or 225 μg at the time of TE resulted in IOP values persistently < 10 mmHg over the three month postoperative observation period.

Published
2017
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2. First-in-human phase I study of ISTH0036, an antisense oligonucleotide selectively targeting transforming growth factor beta 2 (TGF-β2), in subjects with open-angle glaucoma undergoing glaucoma filtration surgery

Author

Martin Feindor, Bogomil Voykov, Melanie Weigel, Katharina Bell, Hagen Thieme, Paul Richter, Katrin Lorenz, Regina Römmich, Michel Janicot, Barbara Wilhelm, Giulia Renieri, Katja Wosikowski, Petra Fettes, Daniela Päckert, Eugen Leo, Carola Mala, and Norbert Pfeiffer

Subjects
0301 basic medicine, Male, Intraocular pressure, Visual acuity, Eye Diseases, genetic structures, Vision, medicine.medical_treatment, Visual Acuity, Oligonucleotides, Glaucoma, Social Sciences, lcsh:Medicine, Cornea, 0302 clinical medicine, Medicine and Health Sciences, Medicine, Trabeculectomy, Psychology, Prospective Studies, Prospective cohort study, Glaucoma Drainage Implants, lcsh:Science, Multidisciplinary, Ophthalmic Procedures, Middle Aged, Tolerability, Transforming Growth Factors, Sensory Perception, Female, medicine.symptom, Anatomy, Glaucoma, Open-Angle, Research Article, medicine.medical_specialty, Open angle glaucoma, Ocular Anatomy, Surgical and Invasive Medical Procedures, Optic Disc, 03 medical and health sciences, Musculoskeletal System Procedures, Ocular System, Ophthalmology, Humans, Aged, business.industry, Mitomycin C, lcsh:R, Biology and Life Sciences, Oligonucleotides, Antisense, medicine.disease, eye diseases, 030104 developmental biology, 030221 ophthalmology & optometry, Eyes, lcsh:Q, sense organs, business, Head, Neuroscience
Abstract

PURPOSE To evaluate the safety and tolerability of intravitreal ISTH0036, an antisense oligonucleotide selectively targeting transforming growth factor beta 2 (TGF-β2), in patients with primary open angle glaucoma (POAG) undergoing trabeculectomy (TE; glaucoma filtration surgery). METHODS In this prospective phase I trial glaucoma patients scheduled for TE with mitomycin C (MMC) received 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 approximately 0.3 μM, 1 μM, 3 μM or 10 μM after injection, respectively. Outcomes assessed included: type and frequency of adverse events (AEs), intraocular pressure (IOP), numbers of interventions post trabeculectomy, bleb survival, visual acuity, visual field, electroretinogram (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 too high or too low IOP, among others. No AE was reported to be related to ISTH0036. All other safety-related analyses did not reveal any toxicities of concern, either. The mean medicated preoperative IOP at decision time-point for surgery 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 for dose levels 1 and 2, IOP values for dose levels 3 and 4 persistently remained below 10 mmHg throughout the observation period. CONCLUSION This first-in-human trial demonstrates that intravitreal injection of ISTH0036 at the end of TE is safe. Regarding IOP control, single-dose ISTH0036 administration of 67.5 μg or 225 μg at the time of TE resulted in IOP values persistently < 10 mmHg over the three month postoperative observation period.

Published
2017

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