Ocular Hypertension, Open Angle Glaucoma
Conditions
Keywords
SYL040012, bamosiran, siRNA, RNAi, Glaucoma, Ocular hypertension
Brief summary
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.
Interventions
DRUG1 drop of 0.375% SYL040012 (bamosiran)
DRUG1 drop of 0.750% SYL040012 (bamosiran)
DRUG1 drop of 1.125% SYL040012 (bamosiran)
DRUG1 drop of 1.5% SYL040012 (bamosiran)
DRUG1 drop of 0.5 % timolol maleate
Sponsors
Sylentis, S.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline in the Mean Diurnal IOP Within Each Treatment Arm | Baseline and Day 28 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Baseline and Day 29 | 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. |
Countries
Estonia, Germany, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SYL040012 (Bamosiran) Eye Drops Dose A 1 drop in each eye once daily for 28 consecutive days
1 drop of SYL040012 (bamosiran) Dose A | 37 |
| SYL040012 (Bamosiran) Eye Drops Dose B 1 drop in each eye once daily for 28 consecutive days
1 drop of SYL040012 (bamosiran) Dose B | 40 |
| SYL040012 (Bamosiran) Eye Drops Dose C 1 drop in each eye once daily for 28 consecutive days
1 drop of SYL040012 (bamosiran) Dose C | 37 |
| SYL040012 (Bamosiran) Eye Drops Dose D 1 drop in each eye once daily for 28 consecutive days
1 drop of SYL040012 (bamosiran) Dose D | 33 |
| Timolol Maleate 0.5% Ophthalmic Solution 1 drop in each eye twice daily for 28 consecutive days
1 drop of timolol maleate: 0.5 % | 37 |
| Total | 184 |
Baseline characteristics
| Characteristic | SYL040012 (Bamosiran) Eye Drops Dose A | SYL040012 (Bamosiran) Eye Drops Dose B | SYL040012 (Bamosiran) Eye Drops Dose C | SYL040012 (Bamosiran) Eye Drops Dose D | Timolol Maleate 0.5% Ophthalmic Solution | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 60.7 years STANDARD_DEVIATION 10.4 | 59.4 years STANDARD_DEVIATION 12.9 | 61.5 years STANDARD_DEVIATION 10.1 | 62.4 years STANDARD_DEVIATION 11.1 | 60.2 years STANDARD_DEVIATION 11.5 | 60.8 years STANDARD_DEVIATION 11.18 |
| Sex: Female, Male Female | 25 Participants | 24 Participants | 22 Participants | 24 Participants | 24 Participants | 119 Participants |
| Sex: Female, Male Male | 12 Participants | 16 Participants | 15 Participants | 9 Participants | 13 Participants | 65 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 37 | 0 / 40 | 0 / 37 | 0 / 33 | 0 / 37 |
| other Total, other adverse events | 4 / 37 | 9 / 40 | 6 / 37 | 2 / 33 | 2 / 37 |
| serious Total, serious adverse events | 0 / 37 | 0 / 40 | 0 / 37 | 0 / 33 | 0 / 37 |
Outcome results
Primary
Change From Baseline in the Mean Diurnal IOP Within Each Treatment Arm
Time frame: Baseline and Day 28
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SYL040012 (Bamosiran) 0.375 % Eye Drops | Change From Baseline in the Mean Diurnal IOP Within Each Treatment Arm | -2.4 mmHg | Standard Deviation 2.6 |
| SYL040012 (Bamosiran) 0.75 % Eye Drops | Change From Baseline in the Mean Diurnal IOP Within Each Treatment Arm | -3.2 mmHg | Standard Deviation 3.9 |
| SYL040012 (Bamosiran) 1.125% Eye Drops | Change From Baseline in the Mean Diurnal IOP Within Each Treatment Arm | -3.1 mmHg | Standard Deviation 2.5 |
| SYL040012 (Bamosiran) 1.5% Eye Drops | Change From Baseline in the Mean Diurnal IOP Within Each Treatment Arm | -3.1 mmHg | Standard Deviation 3.2 |
| Timolol Maleate 0.5% Ophthalmic Solution | Change From Baseline in the Mean Diurnal IOP Within Each Treatment Arm | -6.1 mmHg | Standard Deviation 2.2 |
p-value: 0.93ANCOVA
p-value: 0.92ANCOVA
p-value: 0.23ANCOVA
p-value: 0.85ANCOVA
p-value: 0.25ANCOVA
p-value: 0.18ANCOVA
Secondary
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.
Time frame: Baseline and Day 29
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SYL040012 (Bamosiran) 0.375 % Eye Drops | Change From Baseline in the Glaucoma Quality of Life Questionnaire (GQL-15) Scores Within Each Treatment Arm | 20 units on a scale | Standard Deviation 8.28 |
| SYL040012 (Bamosiran) 0.75 % Eye Drops | Change From Baseline in the Glaucoma Quality of Life Questionnaire (GQL-15) Scores Within Each Treatment Arm | 20.7 units on a scale | Standard Deviation 7.68 |
| SYL040012 (Bamosiran) 1.125% Eye Drops | Change From Baseline in the Glaucoma Quality of Life Questionnaire (GQL-15) Scores Within Each Treatment Arm | 19.4 units on a scale | Standard Deviation 6.34 |
| SYL040012 (Bamosiran) 1.5% Eye Drops | Change From Baseline in the Glaucoma Quality of Life Questionnaire (GQL-15) Scores Within Each Treatment Arm | 22 units on a scale | Standard Deviation 9.65 |
| Timolol Maleate 0.5% Ophthalmic Solution | Change From Baseline in the Glaucoma Quality of Life Questionnaire (GQL-15) Scores Within Each Treatment Arm | 18.7 units on a scale | Standard Deviation 6.21 |
Secondary
Change From Baseline in the Mean Diurnal IOP Within Each Treatment Arm
Time frame: Baseline and Day 14
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SYL040012 (Bamosiran) 0.375 % Eye Drops | Change From Baseline in the Mean Diurnal IOP Within Each Treatment Arm | -2.4 mmHg | Standard Deviation 2.6 |
| SYL040012 (Bamosiran) 0.75 % Eye Drops | Change From Baseline in the Mean Diurnal IOP Within Each Treatment Arm | -2.9 mmHg | Standard Deviation 2.4 |
| SYL040012 (Bamosiran) 1.125% Eye Drops | Change From Baseline in the Mean Diurnal IOP Within Each Treatment Arm | -2.5 mmHg | Standard Deviation 2.1 |
| SYL040012 (Bamosiran) 1.5% Eye Drops | Change From Baseline in the Mean Diurnal IOP Within Each Treatment Arm | -2.4 mmHg | Standard Deviation 3.1 |
| Timolol Maleate 0.5% Ophthalmic Solution | Change From Baseline in the Mean Diurnal IOP Within Each Treatment Arm | -5.8 mmHg | Standard Deviation 1.9 |
p-value: 0.94ANCOVA
p-value: 0.38ANCOVA
p-value: 0.85ANCOVA
p-value: 0.412ANCOVA
p-value: 0.79ANCOVA
p-value: 0.28ANCOVA