Phase I Dose Escalation Study to Investigate the Safety of ISTH0036 in Subjects With Glaucoma Undergoing Trabeculectomy

Phase 1

Completed

• Conditions: Primary Open Angle Glaucoma
• Interventions: Drug: TGF-β2 antisense oligonucleotide; Procedure: Trabeculectomy

• Registration Number: NCT02406833
• Lead Sponsor: Isarna Therapeutics GmbH

Brief Summary

This study evaluates the addition of ISTH0036, an antisense oligonucleotide against TGF-β2, to glaucoma filtration surgery (trabeculectomy). The treatment aims at improving the surgery outcome by prevention of excessive scarring and trabecular meshwork transformation.

Detailed Description

The transforming growth factor beta (TGF-β) is known to play a key role in glaucoma. Increased levels of TGF-β2 in the eye have been linked to trabecular meshwork transformation, increased intraocular pressure and direct optic nerve damage.

Trabeculectomy is the standard surgical intervention to reduce intraocular pressure in subjects no longer sufficiently responding to pressure-lowering medications. Scarring of the surgically opened canal (bleb) often abolishes the effect of trabeculectomy (despite the intraoperative use of Mitomycin C to prevent this). TGF-β2 has been described to play a distinct role in the fibrotic process of bleb closure.

Study Timeline

• Study First Submitted: 2015-03-25
• Study First Submitted QC: 2015-03-30
• Study Start: 2015-04
• Study First Posted: 2015-04-02
• Primary Completion: 2016-08
• Study Completion: 2017-08
• Status Verified: 2018-02
• Last Update Submitted: 2018-02-27
• Last Update Posted: 2018-02-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 13

Inclusion Criteria

• Subject scheduled for trabeculectomy with Mitomycin C
• Subject no longer tolerating or benefitting from pharmacologic treatment of glaucoma

Exclusion Criteria

• History of relevant ocular trauma < 6 months or ocular infection/inflammation < 3 months
• severe central visual field loss within 6 months unrelated to glaucoma
• pregnant or nursing women or subjects not using adequate contraception
• history or evidence of any other clinically significant disorder, condition or disease that would pose a risk to subject safety or interfere with study evaluations, procedures or interpretation

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
TGF-β2 antisense oligonucleotide	TGF-β2 antisense oligonucleotide	Core Study: Administered intravitreally at the time of trabeculectomy at escalating doses Post-Study Follow-up: until 1 year after administration
TGF-β2 antisense oligonucleotide	Trabeculectomy	Core Study: Administered intravitreally at the time of trabeculectomy at escalating doses Post-Study Follow-up: until 1 year after administration

Primary Outcome Measures

Name	Time	Method
Safety and tolerability as assessed by clinical monitoring and reporting of adverse events (AE) and serious adverse events (SAE)	1 year

Secondary Outcome Measures

Name	Time	Method
Intraocular pressure	1 year
Number of interventions post trabeculectomy	1 year
Visual field	1 year

Trial Locations

Locations (3)

University Hospital Magdeburg, Ophthalmology; 🇩🇪 Magdeburg, Germany

Department of Ophthalmology, Johannes-Gutenberg University Mainz; 🇩🇪 Mainz, Germany

University of Tuebingen, Center of Ophthalmology; 🇩🇪 Tuebingen, Germany