E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to severe dry eye disease (DED) |
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E.1.1.1 | Medical condition in easily understood language |
Moderate to severe dry eye |
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10013774 |
E.1.2 | Term | Dry eye |
E.1.2 | System Organ Class | 10015919 - Eye disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Assessment of efficacy of SYL1001 at 11.25 mg/mL on signs and symptoms of DED |
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E.2.2 | Secondary objectives of the trial |
Safety assessment : local and systemic tolerability, and Adverse Events |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patient is a male or a female aged ≥ 18 years at screening visit
2. Have given their written consent to participate in the study, after having received all information relating to the design, aims and possible risks resulting therefrom.
3. Common symptoms of persistent, daily, moderate to severe dry eye lasting more than six months.
4. Use of artificial tears during the last 30 days prior to the selection phase
5. VAS scale for eye discomfort/pain between 30 - 80 in one of the eyes and ≥ 20 in the fellow eye.
6. CFS ≥ 2 and ≤ 4 on the Oxford scale (0-5) in at least 1 eye region in the eye with the highest VAS scoring for eye discomfort/pain.
7. TBUT < 10 seconds in the eye with the highest VAS scoring for eye discomfort/pain. TBUT ≥1 in both eyes.
8. Hyperemia score ≥1 (McMonnies scale) in the eye with the highest VAS scoring for eye discomfort/pain.
9. Schirmer's test without anesthesia ≥ 2 and < 10 mm/5min in the eye with the highest VAS scoring for eye discomfort/pain. Value ≥ 2 in the fellow eye.
10. Corrected visual acuity ≤ 0.7 logMAR (≥20/100 Snellen or ≥ 50 ETDRS) in both eyes.
11. If the subject is selected in a French site, he/she must be covered by a National Social Security System at screening visit.
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E.4 | Principal exclusion criteria |
1. Pregnant or breastfeeding females or females with a positive pregnancy test at the screening visits.
2. Females of childbearing potential not willing to use a medically acceptable contraceptive method from enrolment until after the final visit. Medically acceptable contraceptive methods include vasectomised sexual partner, bilateral tubal ligation, intrauterine devices or implants, normal or low dose combination oral pills, injectable contraceptive, ethinylestradiol transdermal system intravaginal devices and use of condoms. True sexual abstinence (starting from enrollment until after the follow-up visit) is also an acceptable contraceptive method.
3. Current, previous chronic or recurrent medical condition which, according to the investigator, might impact the interpretation of the study results or put the subject at risk.
4. Current concomitant use of any medications with analgesic activity (such as regular pain killer users) by any route of administration at the time of entry into the study and during the study.
5. Change in concomitant systemic medication one month before the study and during the study that might impact the interpretation of the results according to the investigator.
6. Concomitant treatment with cyclosporine, tacrolimus, sirolimus (systemic or ophthalmic) for the previous 2 months before entering the study.
7. Any eye concomitant treatment at the time of entry into the study. Unpreserved artificial tears will be provided by the Sponsor to use throughout the study. A maximum of 4 daily drops is allowed.
8. History of hypersensitivity to SYL1001, to any component of the formulation or to ophthalmic diagnostic agents.
9. Use of contact lenses or presence of punctal plugs during the treatment and the previous 7 days (prior to treatment initiation).
10. Clinically significant laboratory abnormalities according to investigator's opinion.
11. Previous refractive surgery, cornea transplant. Meibomian gland dysfunction or history of lid malposition (ectropion, entropion, ptosis) history of recurrent corneal herpes or history of recurrent corneal erosion or neurotrophic keratopathy (that may affect acurate assessment of the disease and/or mask the effects of the drug)
12. Any other ocular surgery in the past 1 year.
13. Any other eye disease that is significant in the investigator's opinion.
14. Currently participating or having participated in another clinical trial within the 2 months prior to inclusion. Patient that already participated in SYL1001_IV trial.
15. Non-compliance after the run-in period.
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E.5 End points |
E.5.1 | Primary end point(s) |
o Change from Baseline in Visual Analogue Scale (VAS) scores for eye discomfort/pain after 28 days of treatment
o Change from Baseline in Corneal Fluorescein Staining (CFS) total scores obtained on the Oxford scale after 28 days of treatment
o Change from Baseline in conjunctival hyperaemia scores based on the McMonnies scale after 28 days of treatment
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
o Change from baseline in VAS scores for eye discomfort/pain at Day 14
o Change from baseline in each of the scores of the dry eye symptoms index (DESI) after 14 and 28 days of treatment
o Change from baseline in CFS total scores obtained on the Oxford scale ater 14 days of treatment
o Change from baseline in CFS central, nasal, temporal, superior and inferior scoring after 14 and 28 days of treatment
o Change from baseline in conjunctival hyperaemia scores based on the McMonnies scale after 14 days of treatment
o Change from baseline in Tear break-up lime (TBUT) and conjunctival staining scores after 14 and 28 days of treatment
o Change from baseline in Schirmer's tests values at Days 14 and 28.
o Number of artificial tears drops per day
o Assessment of the impact of treatment on the QoL (NEI-VFQ) questionnaire at Day 28.
o Assessment of the impact of treatment on the Clinical Global Impression Questionnaires (Clinician and Subject) at Day 28.
o Assessment of the impact of treatment on local and systemic tolerability.
o Assessment of other Adverse Events (AEs) occurrence |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Day 14 and Day 28
Throughout the study for tolerability and Adverse Events |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 31 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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
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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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |