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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase I, Open-Label, Dose-Escalation Study to Investigate the Safety of ISTH0036, a 'Next Generation' TGF-β2-Selective Antisense Oligonucleotide, in Subjects With Primary Open-Angle Glaucoma Undergoing Trabeculectomy

Conditions
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Primary Open Angle Glaucoma

Intervention / Treatment
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* Drug: TGF-β2 antisense oligonucleotide
* Procedure: Trabeculectomy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TGF-β2 antisense oligonucleotide<br>Core Study: Administered intravitreally at the time of trabeculectomy at escalating doses Post-Study Follow-up: until 1 year after administration | Drug: TGF-β2 antisense oligonucleotide<br>* intravitreal injection<br>* Other names: ISTH0036;Procedure: Trabeculectomy<br>* Standard trabeculectomy with the use of antimetabolites (mitomycin C) for glaucoma patients with insufficient intraocular pressure (IOP) control<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability as assessed by clinical monitoring and reporting of adverse events (AE) and serious adverse events (SAE) |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intraocular pressure |  | 1 year | 
| Number of interventions post trabeculectomy |  | 1 year | 
| Visual field |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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glaucoma, trabeculectomy