SYLTAG: SYL040012, Treatment for Open Angle Glaucoma

• Sponsor: Sylentis, S.A. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02250612
• Collaborator: (none)
• Enrollment: 184
• Locations: 21
• Arms: 5
• Duration (Months): 15
• Patients Per Site: 8.8
• Patients Per Site Per Month: 0.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Open Angle Glaucoma; Ocular Hypertension	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	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 184 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: Oct 1, 2014
• Actual Primary Completion Date: Aug 1, 2015
• Actual Study Completion Date: Jan 1, 2016

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in the Mean Diurnal IOP Within Each Treatment Arm [Baseline and Day 28]

Secondary Outcome Measures

1. Change From Baseline in the Mean Diurnal IOP Within Each Treatment Arm [Baseline and Day 14]

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sall Research Medical Center	Artesia	California	United States	90701
2	North Bay Eye Associates	Petaluma	California	United States	94954
3	Eye Care Centers Management, Inc (Clayton Eye Center)	Morrow	Georgia	United States	30260
4	Taustin Eye Center	Louisville	Kentucky	United States	40217
5	East Tallin Central Hospital	Tallin		Estonia	10138
6	Eye Clinic Dr. Krista Turman	Tallin		Estonia	13419
7	Tartu University Hospital	Tartu		Estonia	50406
8	Universitaetsklinikum Freiburg	Freiburg		Germany	79106
9	University Clinic Magdeburg	Magdeburg		Germany	39106
10	Klinikum der Universität München	München		Germany	80336
11	Universitätsklinikum Münster	Münster		Germany	D-48149
12	University Hospital Regensburg	Regensburg		Germany	93053
13	Hospital de Torrevieja	Torrevieja	Alicante	Spain	03186
14	Hospital de Jerez	Jerez de la Frontera	Cádiz	Spain	11407
15	Clinica Universidad Navarra	Pamplona	Navarra	Spain	31008
16	Hospital Clinic	Barcelona		Spain	08036
17	Hospital Universitario Ramón y Cajal	Madrid		Spain	28034
18	Hospital Universitario Clínico San Carlos	Madrid		Spain	28040
19	Complejo Hospitalario de Pontevedra	Pontevedra		Spain	36001
20	Instituto de Oftalmobiología Aplicada	Valladolid		Spain	47011
21	Hospital Universitario Miguel Servet	Zaragoza		Spain	50009

Sponsors and Collaborators

• Sylentis, S.A.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sylentis, S.A.
• ClinicalTrials.gov Identifier: NCT02250612
• Other Study ID Numbers: SYL040012_IV; 2013-002947-27
• First Posted: Sep 26, 2014
• Last Update Posted: Jan 6, 2021
• Last Verified: Dec 1, 2020

• Keywords provided by Sylentis, S.A.: SYL040012; bamosiran; siRNA; RNAi; Glaucoma; Ocular hypertension
• Additional relevant MeSH terms: Glaucoma; Glaucoma, Open-Angle; Ocular Hypertension; Hypertension; Timolol

Study Results

Participant Flow

Arm/Group Title	SYL040012 (Bamosiran) 0.375% Eye Drops	SYL040012 (Bamosiran) 0.750 % Eye Drops	SYL040012 (Bamosiran) 1.125% Eye Drops	SYL040012 (Bamosiran) 1.5% Eye Drops	Timolol Maleate 0.5% Ophthalmic Solution
Arm/Group Description	1 drop in each eye once daily for 28 consecutive days 1 drop of SYL040012 (bamosiran) 0.375 %	1 drop in each eye once daily for 28 consecutive days 1 drop of SYL040012 (bamosiran) 0.750 %	1 drop in each eye once daily for 28 consecutive days 1 drop of SYL040012 (bamosiran) 1.125%	1 drop in each eye once daily for 28 consecutive days 1 drop of SYL040012 (bamosiran) 1.5%	1 drop in each eye twice daily for 28 consecutive days 1 drop of timolol maleate: 0.5 %
Period Title: Overall Study
STARTED	37	40	37	33	37
COMPLETED	36	38	35	33	36
NOT COMPLETED	1	2	2	0	1

Baseline Characteristics

Arm/Group Title	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
Arm/Group Description	1 drop in each eye once daily for 28 consecutive days 1 drop of SYL040012 (bamosiran) Dose A	1 drop in each eye once daily for 28 consecutive days 1 drop of SYL040012 (bamosiran) Dose B	1 drop in each eye once daily for 28 consecutive days 1 drop of SYL040012 (bamosiran) Dose C	1 drop in each eye once daily for 28 consecutive days 1 drop of SYL040012 (bamosiran) Dose D	1 drop in each eye twice daily for 28 consecutive days 1 drop of timolol maleate: 0.5 %	Total of all reporting groups
Overall Participants	37	40	37	33	37	184
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.7 (10.4)	59.4 (12.9)	61.5 (10.1)	62.4 (11.1)	60.2 (11.5)	60.8 (11.18)
Sex: Female, Male (Count of Participants)
Female	25 67.6%	24 60%	22 59.5%	24 72.7%	24 64.9%	119 64.7%
Male	12 32.4%	16 40%	15 40.5%	9 27.3%	13 35.1%	65 35.3%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in the Mean Diurnal IOP Within Each Treatment Arm
Time Frame	Baseline and Day 28

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SYL040012 (Bamosiran) 0.375 % Eye Drops	SYL040012 (Bamosiran) 0.75 % Eye Drops	SYL040012 (Bamosiran) 1.125% Eye Drops	SYL040012 (Bamosiran) 1.5% Eye Drops	Timolol Maleate 0.5% Ophthalmic Solution
Arm/Group Description	1 drop in each eye once daily for 28 consecutive days 1 drop of SYL040012 (bamosiran) 0.375 %	1 drop in each eye once daily for 28 consecutive days 1 drop of SYL040012 (bamosiran) 0.75%	1 drop in each eye once daily for 28 consecutive days 1 drop of SYL040012 (bamosiran) 1.125%	1 drop in each eye once daily for 28 consecutive days 1 drop of SYL040012 (bamosiran) 1.5%	1 drop in each eye twice daily for 28 consecutive days 1 drop of timolol maleate: 0.5 %
Measure Participants	36	38	35	33	35
Mean (Standard Deviation) [mmHg]	-2.4 (2.6)	-3.2 (3.9)	-3.1 (2.5)	-3.1 (3.2)	-6.1 (2.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SYL040012 (Bamosiran) 1.125% Eye Drops, SYL040012 (Bamosiran) 1.5% Eye Drops
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.93
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	SYL040012 (Bamosiran) 0.75 % Eye Drops, SYL040012 (Bamosiran) 1.5% Eye Drops
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.92
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	SYL040012 (Bamosiran) 0.375 % Eye Drops, SYL040012 (Bamosiran) 1.5% Eye Drops
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.23
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	SYL040012 (Bamosiran) 0.75 % Eye Drops, SYL040012 (Bamosiran) 1.125% Eye Drops
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.85
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	SYL040012 (Bamosiran) 0.375 % Eye Drops, SYL040012 (Bamosiran) 1.125% Eye Drops
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.25
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	SYL040012 (Bamosiran) 0.375 % Eye Drops, SYL040012 (Bamosiran) 0.75 % Eye Drops
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.18
	Comments
	Method	ANCOVA
	Comments

2. Secondary Outcome

Title	Change From Baseline in the Mean Diurnal IOP Within Each Treatment Arm
Time Frame	Baseline and Day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SYL040012 (Bamosiran) 1.5% Eye Drops	SYL040012 (Bamosiran) Eye Drops 1.125%	SYL040012 (Bamosiran) Eye Drops 0.75%	SYL040012 (Bamosiran) 0.375 % Eye Drops	Timolol Maleate 0.5% Ophthalmic Solution
Arm/Group Description	1 drop in each eye once daily for 28 consecutive days 1 drop of SYL040012 (bamosiran) 1.5%	1 drop in each eye once daily for 28 consecutive days 1 drop of SYL040012 (bamosiran) 1.125%	1 drop in each eye once daily for 28 consecutive days 1 drop of SYL040012 (bamosiran) 0.75%	1 drop in each eye once daily for 28 consecutive days 1 drop of SYL040012 (bamosiran) 0.375 %	1 drop in each eye twice daily for 28 consecutive days 1 drop of timolol maleate: 0.5 %
Measure Participants	36	38	35	33	35
Mean (Standard Deviation) [mmHg]	-2.4 (2.6)	-2.9 (2.4)	-2.5 (2.1)	-2.4 (3.1)	-5.8 (1.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SYL040012 (Bamosiran) 0.375 % Eye Drops, SYL040012 (Bamosiran) 0.75 % Eye Drops
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.94
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	SYL040012 (Bamosiran) 0.375 % Eye Drops, SYL040012 (Bamosiran) 1.125% Eye Drops
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.38
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	SYL040012 (Bamosiran) 0.375 % Eye Drops, SYL040012 (Bamosiran) 1.5% Eye Drops
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.85
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	SYL040012 (Bamosiran) 0.75 % Eye Drops, SYL040012 (Bamosiran) 1.125% Eye Drops
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.412
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	SYL040012 (Bamosiran) 0.75 % Eye Drops, SYL040012 (Bamosiran) 1.5% Eye Drops
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.79
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	SYL040012 (Bamosiran) 1.125% Eye Drops, SYL040012 (Bamosiran) 1.5% Eye Drops
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.28
	Comments
	Method	ANCOVA
	Comments

3. Secondary Outcome

Title	Change From Baseline in the Glaucoma Quality of Life Questionnaire (GQL-15) Scores Within Each Treatment Arm
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SYL040012 (Bamosiran) 1.5% Eye Drops	SYL040012 (Bamosiran) 1.125% Eye Drops	SYL040012 (Bamosiran) 0.75% Eye Drops	SYL040012 (Bamosiran) Eye Drops 0.375%	Timolol Maleate 0.5% Ophthalmic Solution
Arm/Group Description	1 drop in each eye once daily for 28 consecutive days 1 drop of SYL040012 (bamosiran) 1.5%	1 drop in each eye once daily for 28 consecutive days 1 drop of SYL040012 (bamosiran) 1.125%	1 drop in each eye once daily for 28 consecutive days 1 drop of SYL040012 (bamosiran) 0.75%	1 drop in each eye once daily for 28 consecutive days 1 drop of SYL040012 (bamosiran) 0.375%	1 drop in each eye twice daily for 28 consecutive days 1 drop of timolol maleate: 0.5 %
Measure Participants	36	38	35	33	35
Mean (Standard Deviation) [units on a scale]	20 (8.28)	20.7 (7.68)	19.4 (6.34)	22 (9.65)	18.7 (6.21)

Adverse Events

Time Frame	28 days
Arm/Group Title	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
Arm/Group Description	1 drop in each eye once daily for 28 consecutive days 1 drop of SYL040012 (bamosiran) Dose A		1 drop in each eye once daily for 28 consecutive days 1 drop of SYL040012 (bamosiran) Dose B		1 drop in each eye once daily for 28 consecutive days 1 drop of SYL040012 (bamosiran) Dose C		1 drop in each eye once daily for 28 consecutive days 1 drop of SYL040012 (bamosiran) Dose D		1 drop in each eye twice daily for 28 consecutive days 1 drop of timolol maleate: 0.5 %
All Cause Mortality
	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
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/37 (0%)		0/40 (0%)		0/37 (0%)		0/33 (0%)		0/37 (0%)
Serious Adverse Events
	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
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/37 (0%)		0/40 (0%)		0/37 (0%)		0/33 (0%)		0/37 (0%)
Other (Not Including Serious) Adverse Events
	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
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/37 (10.8%)		9/40 (22.5%)		6/37 (16.2%)		2/33 (6.1%)		2/37 (5.4%)
Eye disorders
Conjunctival hyperaemia	1/37 (2.7%)	2	0/40 (0%)	0	3/37 (8.1%)	3	2/33 (6.1%)	2	1/37 (2.7%)	1
Eye pruritus	2/37 (5.4%)	2	1/40 (2.5%)	1	0/37 (0%)	0	0/33 (0%)	0	1/37 (2.7%)	1
Lacrimation increased	0/37 (0%)	0	2/40 (5%)	2	0/37 (0%)	0	0/33 (0%)	0	0/37 (0%)	0
Ocular discomfort	0/37 (0%)	0	3/40 (7.5%)	3	0/37 (0%)	0	1/33 (3%)	1	0/37 (0%)	0
Vision blurred	0/37 (0%)	0	2/40 (5%)	2	0/37 (0%)	0	0/33 (0%)	0	1/37 (2.7%)	1
Gastrointestinal disorders
Toothache	0/37 (0%)	0	2/40 (5%)	2	0/37 (0%)	0	0/33 (0%)	0	0/37 (0%)	0
Infections and infestations
Nasopharyngitis	2/37 (5.4%)	2	0/40 (0%)	0	1/37 (2.7%)	1	1/33 (3%)	1	0/37 (0%)	0
Investigations
Instillation site pain	0/37 (0%)	0	0/40 (0%)	0	0/37 (0%)	0	0/33 (0%)	0	2/37 (5.4%)	2
Nervous system disorders
Headache	1/37 (2.7%)	1	1/40 (2.5%)	5	3/37 (8.1%)	3	1/33 (3%)	1	0/37 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.