Clinical Trials Register

Summary
EudraCT Number:	2011-001849-33
Sponsor's Protocol Code Number:	SYL040012_III
National Competent Authority:	Estonia - SAM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-03-08
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Estonia - SAM

A.2

EudraCT number

2011-001849-33

A.3

Full title of the trial

DOSE FINDING CLINICAL TRIAL WITH SYL040012 TO EVALUATE THE TOLERABILITY AND EFFECT ON INTRAOCULAR PRESSURE IN SUBJECTS WITH OCULAR HYPERTENSION OR OPEN-ANGLE GLAUCOMA

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Dose Finding Clinical Trial with SYL040012 in subjects with ocular hypertension

A.4.1

Sponsor's protocol code number

SYL040012_III

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1126-6866

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Sylentis S.A.U.
B.1.3.4	Country	Spain
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Sylentis S.A.U.
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Sylentis S.A.U.
B.5.2	Functional name of contact point	Head of Regulatory Affairs & QP
B.5.3	Address:
B.5.3.1	Street Address	Parque Científico, C/Santiago Grisolía, nº 2
B.5.3.2	Town/ city	Tres Cantos (Madrid)
B.5.3.3	Post code	28760
B.5.3.4	Country	Spain
B.5.4	Telephone number	+3491 804 7667
B.5.5	Fax number	+3491 804 9597
B.5.6	E-mail	info@sylentis.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	SYL040012
D.3.4	Pharmaceutical form	Eye drops, solution
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Ocular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	1242615-29-7
D.3.9.2	Current sponsor code	SYL040012
D.3.9.3	Other descriptive name	SYL040012
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2.0
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	SYL040012
D.3.4	Pharmaceutical form	Eye drops, solution
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Ocular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	1242615-29-7
D.3.9.2	Current sponsor code	SYL040012
D.3.9.3	Other descriptive name	SYL040012
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	7.5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	SYL040012
D.3.4	Pharmaceutical form	Eye drops, solution
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Ocular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	1242615-29-7
D.3.9.2	Current sponsor code	SYL040012
D.3.9.3	Other descriptive name	SYL040012
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	22.5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Eye drops, solution
D.8.4	Route of administration of the placebo	Ocular use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Ocular Hypertension or Open-Angle Glaucoma

E.1.1.1

Medical condition in easily understood language

Ocular Hypertension or Glaucoma

E.1.1.2

Therapeutic area

Diseases [C] - Eye Diseases [C11]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10022801
E.1.2	Term	Intraocular pressure
E.1.2	System Organ Class	10022891 - Investigations

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Tolerability in the ocular surface (cornea and conjunctiva) and effect on intraocular pressure after a daily dose of the investigational product during 14 days of treatment

E.2.2

Secondary objectives of the trial

• Local tolerability after each dose.
• Systemic tolerability: Effect on laboratory parameters, physical examination, vital signs and electrocardiogram.
• Changes (if any) of the ocular fundus or visual acuity possibly related to the investigational product.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Signed informed consent prior to any clinical trial-related procedures.
2. Male and female subjects in good or fair general health as assessed by the investigator.
3. Age ≥18 years.
4. Previous history or newly diagnosed IOP (≥21 mmHg) with or without open-angle glaucoma in both eyes.
5. Normal result, or result typical for open-angle glaucoma of the following assessments in both eyes or available results in writting within the last 3 months prior to baseline period i.e. up to 4 months before Day 1, on condition that no new ocular signs or symptoms (e.g. marked deterioration of vision, eye pain) has occurred since then which would justify a repeat examination:
- Visual field 24-2 or equivalent (24-2 Humphrey visual field SITA test, about 5 minutes per eye).
- Optical coherence tomography (OCT).
- Best corrected visual acuity ≥0.5 (20/40) on the Snellen chart, or ≤0.3 logMAR.
- Schirmer test (lacrimation).
- Funduscopy.

E.4

Principal exclusion criteria

Exclusion criteria related to general health
1. Pregnant or breastfeeding females or females with a positive urine pregnancy test at the baseline period and on Day 1 of the treatment period.
2. Females of childbearing potential not willing to use a medically acceptable contraceptive method from enrolment until after the follow-up visit.
• Females of childbearing potential are defined as females who are not post menopausal (amenorrheic without an alternative medical cause) or have not been irreversibly surgical sterilised by hysterectomy, bilateral oophorectomy or bilateral salpingectomy.
• Medically acceptable contraceptive methods include vasectomised sexual partner, tubal occlusion, intrauterine device (copper banded coils only), intrauterine system (for example, Mirena), Depo-Provera, implants (Implanon, Norplan), normal and low dose combined oral pills, ethinylestradiol transdermal system (Evra Patch), and intravaginal device (NuvaRing). True sexual abstinence (starting from enrolment until after the follow-up visit) is also an acceptable contraceptive method.
3. Any current disease or condition that might compromise the respiratory, cardiovascular, endocrine, neurological, haematological, renal, or gastrointestinal function (unless deemed not clinically significant by the investigator and sponsor) such as, but not limited to, uncontrolled arterial hypertension (defined as systolic blood pressure [SBP] >160 mmHg or diastolic blood pressure [DBP] >95 mmHg with or without treatment), acute infection in any of the above mentioned systems, uncontrolled type 1 or type 2 diabetes (defined as persistently varying glucose values, receiving multiple insulin injections per day), bronchial asthma requiring frequent use of corticosteroids, or heart failure (New York Heart Association [NYHA] ≥grade 2).
4. Past history of a chronic or recurring condition that could interfere with treatment according to the investigator’s judgement. History of cancer in the last 5 years (except for cutaneous basal or squamous cell carcinoma resolved by excision).
5. Body temperature (axillary, oral or external auditory canal) ≥37.5°C (only to be checked at the enrolment visit).
6. Intolerability of any components of SYL040012 or placebo.
7. Unable to comply with the clinical trial requirements as judged by the investigator.

Exclusion criteria related to medications or procedures
8. Beta blockers or corticosteroids (other than cutaneous or intra-articular) for the treatment of concurrent diseases, even if sporadically, or any ocular or nasal vasoconstrictor treatment in the last 15 days prior to the first investigational product administration
9. Previous refractive surgery; cataract extraction in the last 6 months.
10. Previous surgery for glaucoma.
11. Participation in a clinical trial within 2 months before the enrolment visit.
12. Use of any other investigational product within 60 days before the enrolment visit.
13. Other drugs for the treatment of concurrent diseases are allowed. However, their dosages should be kept constant throughout the study.

Exclusion criteria related to ocular conditions
14. Use of contact lenses in the last 7 days prior to the first investigational product administration and wearing contact lenses throughout the trial.
15. History of ocular infection or inflammation within the last 3 months before the enrolment visit.
16. Pachymetry result (in the middle of the cornea) >620 micron or <500 micron.
17. Angle-closure or pigmentary glaucoma.
18. Chronic or current acute eye diseases such as scleritis, uveitis, blepharitis, conjunctivitis, or ocular Herpes simplex virus infection.
19. Cup to disc (C/D) ratio more than 0.8.
20. Impossibility to properly visualise the ocular fundus, for example due to vitreous haemorrhage or advanced cataract.

Exclusion criteria related to laboratory findings
21. Relevant abnormal laboratory results as judged by the investigator.
22. Positive screening for hepatitis C virus, hepatitis B surface antigen or human immunodeficiency virus (HIV).

E.5 End points

E.5.1

Primary end point(s)

Local tolerability:
Includes simple corneal and conjunctival evaluation without corneal endothelium assessment or pachymetry. A slit lamp will be used.
The local tolerability evaluation will include:
Cornea: Corneal epithelium using fluorescein and Bengal pink dye.
Conjunctiva: Palpebral and bulbar conjunctival hyperaemia.
A VAS will be used to assess local tolerability in case of symptoms:
0 = no ocular discomfort and 100 = severe ocular discomfort.

The tolerability variable can be categorised as:
Normal: No corneal or conjunctival alteration observed.
Grade 1: Symptomatic or minimally symptomatic alterations observed, but which do not require intervention or interfere with function.
Grade 2: Symptomatic alterations observed which interfere with the function but not with daily life, and require topical intervention.
Grade 3: Symptomatic alterations observed which interfere with daily life, and require surgical intervention.
This classification is based on Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03

E.5.1.1

Timepoint(s) of evaluation of this end point

Continuously during the whole trial and in a daily basis: days 1 to 15 and in the follow-up visit/early termination visit days.

E.5.2

Secondary end point(s)

• Anterior segment of the eye
• Visual acuity
• Ocular fundus
• Physical examination and vital signs
• Laboratory analyses (haematology, biochemistry, and urinalysis)
• 12-Lead ECG
• Recording of AEs
• VAS of local tolerability in case of symptoms (0 = no ocular discomfort and 100 = severe ocular discomfort).

E.5.2.1

Timepoint(s) of evaluation of this end point

Continuously during the whole trial.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The clinical trial will consist of a baseline period, a treatment period and a follow-up visit.
For each subject the duration of the clinical trial will be approximately 7 weeks.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Following study completion, investigators should continue treatment of the subject's condition at their discretion with consideration to available licensed products for the treatment of glaucoma.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2012-04-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-03-15

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-04-30

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