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

Isarna Therapeutics

Status and phase: Completed; Phase 1

Conditions: Primary Open Angle Glaucoma

Treatments: Drug: TGF-β2 antisense oligonucleotide; Procedure: Trabeculectomy

Study type: Interventional

Funder types: Industry

Identifiers

NCT02406833

ISTH-01-111

2014-004985-74 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 13 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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13 participants in 1 patient group

TGF-β2 antisense oligonucleotide

Experimental group

Description:

Core Study: Administered intravitreally at the time of trabeculectomy at escalating doses Post-Study Follow-up: until 1 year after administration

Treatment:

Procedure: Trabeculectomy

Drug: TGF-β2 antisense oligonucleotide