SYL040012, Treatment for Open Angle Glaucoma

Study Overview
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Brief Summary
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The purpose of this double-masked, randomized, controlled study is to assess the safety and ocular hypotensive efficacy of four different doses of SYL040012 (bamosiran) eye drops compared to Timolol maleate 0.5% after 28 treatment days in patients with elevated intraocular pressure.

Official Title
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A Phase II, Observer Masked, Active Controlled Study of SYL040012 for the Treatment of Elevated Intraocular Pressure in Patients With Open-angle Glaucoma or Ocular Hypertension

Conditions
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Open Angle Glaucoma, Ocular Hypertension

Intervention / Treatment
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* Drug: 1 drop of 0.375% SYL040012 (bamosiran)
* Drug: 1 drop of 0.750% SYL040012 (bamosiran)
* Drug: 1 drop of 1.125% SYL040012 (bamosiran)
* Drug: 1 drop of 1.5% SYL040012 (bamosiran)
* Drug: 1 drop of 0.5 % timolol maleate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients older than 18 years of either sex Good or fair general health as assessed by the investigator. Signed informed consent prior to any clinical trial-related procedures Diagnosis of open angle glaucoma (OAG) or ocular hypertension (OHT) Post-washout mean IOP above target range BCVA 1.0 logMAR or better by ETDRS in each eye (equivalent to 20/200) Stable visual field Central corneal thickness 480-620 μm Shaffer gonioscopic grade of ≥ 3 (in at least 3 quadrants) in both eyes Exclusion Criteria: Pregnant or breastfeeding females Females of childbearing potential not willing to use a medically acceptable contraceptive method Clinically significant systemic disease Changes of systemic medication that could have a substantial effect on IOP Known hypersensitivity to any component of the formulations Unable to comply with the clinical trial requirements Clinically significant abnormalities in laboratory tests Severe visual field defect Any secondary glaucoma Pseudoexfoliation or pigment dispersion component, history of angle closure or narrow angles. IOP ≥ 35 mm Hg in any eye Previous non-laser glaucoma surgery or glaucoma laser procedures (e.g., laser trabeculoplasty) and refractive surgery Any ocular surgery or laser treatment, cataract extraction or ocular trauma within 6 months prior to Baseline Evidence of ocular infection, inflammation, clinically significant blepharitis or conjunctivitis at baseline (Visit 0), or a history of herpes simplex keratitis Clinically significant ocular disease

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SYL040012 (bamosiran) 0.375% eye drops<br>1 drop in each eye once daily for 28 consecutive days | Drug: 1 drop of 0.375% SYL040012 (bamosiran)<br> <br> |
| Experimental: SYL040012 (bamosiran) 0.750% eye drops<br>1 drop in each eye once daily for 28 consecutive days | Drug: 1 drop of 0.750% SYL040012 (bamosiran)<br> <br> |
| Experimental: SYL040012 (bamosiran) 1.125% eye drops<br>1 drop in each eye once daily for 28 consecutive days | Drug: 1 drop of 1.125% SYL040012 (bamosiran)<br> <br> |
| Experimental: SYL040012 (bamosiran) 1.5% eye drops<br>1 drop in each eye once daily for 28 consecutive days | Drug: 1 drop of 1.5% SYL040012 (bamosiran)<br> <br> |
| Active Comparator: Timolol maleate 0.5% ophthalmic solution<br>1 drop in each eye twice daily for 28 consecutive days | Drug: 1 drop of 0.5 % timolol maleate<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Mean Diurnal IOP Within Each Treatment Arm |  | Baseline and Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Mean Diurnal IOP Within Each Treatment Arm |  | Baseline and Day 14 | 
| Change From Baseline in the Glaucoma Quality of Life Questionnaire (GQL-15) Scores Within Each Treatment Arm | The GQL-15 is a 15 item, 4-domain tool. GQL-15 scoring ranges from 0 to 75. Higher scores indicate poorer quality of life. | Baseline and Day 29 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SYL040012, bamosiran, siRNA, RNAi, Glaucoma, Ocular hypertension