SYL040012, Treatment for Open Angle Glaucoma (SYLTAG)

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

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.

Study Overview

• Status: Completed
• Conditions: Ocular Hypertension; Open Angle Glaucoma
• Intervention / Treatment: 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

• Study Type: Interventional
• Enrollment (Actual): 184
• Phase: Phase 2

Contacts and Locations

Study Locations

• Estonia
  • Tallin, Estonia, 10138
    • East Tallin Central Hospital
  • Tallin, Estonia, 13419
    • Eye Clinic Dr. Krista Turman
  • Tartu, Estonia, 50406
    • Tartu University Hospital
• Germany
  • Freiburg, Germany, 79106
    • Universitaetsklinikum Freiburg
  • Magdeburg, Germany, 39106
    • University Clinic Magdeburg
  • München, Germany, 80336
    • Klinikum der Universität München
  • Münster, Germany, D-48149
    • Universitatsklinikum Munster
  • Regensburg, Germany, 93053
    • University Hospital Regensburg
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clínic
  • Madrid, Spain, 28034
    • Hospital Universitario Ramón y Cajal
  • Madrid, Spain, 28040
    • Hospital Universitario Clinico San Carlos
  • Pontevedra, Spain, 36001
    • Complejo Hospitalario de Pontevedra
  • Valladolid, Spain, 47011
    • Instituto de Oftalmobiología Aplicada
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
  • Alicante
    • Torrevieja, Alicante, Spain, 03186
      • Hospital de Torrevieja
  • Cádiz
    • Jerez de la Frontera, Cádiz, Spain, 11407
      • Hospital de Jerez
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Clinica Universidad Navarra
• United States
  • California
    • Artesia, California, United States, 90701
      • Sall Research Medical Center
    • Petaluma, California, United States, 94954
      • North Bay Eye Associates
  • Georgia
    • Morrow, Georgia, United States, 30260
      • Eye Care Centers Management, Inc (Clayton Eye Center)
  • Kentucky
    • Louisville, Kentucky, United States, 40217
      • Taustin Eye Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Sylentis, S.A.

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: September 5, 2014
• First Submitted That Met QC Criteria: September 24, 2014
• First Posted (Estimate): September 26, 2014

Study Record Updates

• Last Update Posted (Actual): January 6, 2021
• Last Update Submitted That Met QC Criteria: December 11, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Ocular hypertension; Glaucoma; siRNA; RNAi; SYL040012; bamosiran
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Glaucoma; Glaucoma, Open-Angle; Ocular Hypertension; Hypertension; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Timolol
• Other Study ID Numbers: SYL040012_IV; 2013-002947-27 (EudraCT Number)