E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to severe dry eye disease (DED) |
Xeroftalmia de moderada a grave |
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E.1.1.1 | Medical condition in easily understood language |
Moderate to severe dry eye |
Sequedad ocular de moderada a grave |
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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 | 19.1 |
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 |
Evaluación de la eficacia de SYL1001 en dosis de 11,25 mg/mL sobre los signos y síntomas de xeroftalmia |
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E.2.2 | Secondary objectives of the trial |
Safety assessment : local and systemic tolerability, and Adverse Events |
Evaluación de la seguridad: tolerabilidad local y sistémica y acontecimientos adversos |
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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. |
1. Pacientes varones o mujeres de 18 o más años de edad en la visita de selección. 2. Han consentido por escrito participar en el estudio, después de haber recibido toda la información relativa al diseño, los objetivos y los posibles riesgos que conlleva dicho estudio. 3. Síntomas habituales de xeroftalmia persistente, diaria, entre moderada e intensa, que duran más de 6 meses. 4. Uso de lágrimas artificiales durante los 30 días previos a la fase de selección. 5. Escala EVA para molestias/dolor oculares entre 30 y 80 en uno de los ojos y al menos ≥ 20 en el otro. 6. TCF ≥ 2 y ≤ 4 en la escala de Oxford (0-5) en al menos una región ocular del ojo con la puntuación más alta en la EVA para molestias/dolor oculares. 7. TRL < 10 segundos en el ojo con la puntuación más alta en la EVA para molestias/dolor oculares. TRL ≥ 1 en ambos ojos. 8. Puntuación de hiperemia ≥ 1 (escala de McMonnies) en el ojo con la puntuación más alta en la EVA para molestias/dolor oculares. 9. Prueba de Schirmer sin anestesia ≥ 2 y < 10 mm/5 min en el ojo con la puntuación más alta en la EVA para molestias/dolor oculares. Valor ≥ 2 en el otro ojo. 10. Agudeza visual corregida ≥ 0,7 logMAR (20/100 Snellen o 50 ETDRS) en ambos ojos. 11. Si el sujeto ha sido seleccionado en un centro francés, debe estar cubierto por el Sistema Nacional de Seguridad Social en la visita de selección. |
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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 documented 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 punctual 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) 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. |
1. Mujeres embarazadas, en fase de lactancia o que obtengan un resultado positivo en la prueba de embarazo de la visita de selección. 2. Mujeres potencialmente fértiles que no estén dispuestas a utilizar un método anticonceptivo médicamente aceptable (definido en la sección 6.3) entre la inclusión y la visita final. 3. Afección médica en curso, crónica previa o recurrente que, según el investigador, pueda influir en la interpretación de los resultados del estudio o poner al sujeto en peligro. 4. El uso concomitante en curso de cualquier medicamento con actividad analgésica (por ejemplo, usuarios habituales de analgésicos) por cualquier vía de administración en el momento de incorporarse al estudio o durante este. 5. Cambio en la medicación sistémica concomitante un mes antes del estudio y durante este que, según el criterio del investigador, pueda influir en la interpretación de los resultados. 6. Tratamiento concomitante con ciclosporina, tacrolimús, sirolimús (sistémico u oftálmico) durante los dos meses previos a la incorporación al estudio. 7. Cualquier tratamiento ocular concomitante en el momento de incorporarse al estudio. El promotor entregará lágrimas artificiales sin conservantes para usarlas a lo largo del estudio. Se permite un máximo de 4 gotas al día. 8. Antecedentes de hipersensibilidad a SYL1001, a cualquier componente de la formulación o a los agentes de diagnóstico oftálmico. 9. Uso de lentes de contacto o tapones lagrimales durante el tratamiento y los 7 días previos (antes de iniciar el tratamiento). 10. Anomalías analíticas clínicamente relevantes en opinión del investigador. 11. Cirugía refractaria o trasplante corneal previos. Disfunción de la glándula de Meibomio o antecedentes de desviación del párpado (ectropión, entropión, ptosis) que puedan afectar a la evaluación precisa de la enfermedad y/u ocultar los efectos del fármaco. 12. Cualquier otra cirugía ocular en el último año. 13. Cualquier otra afección ocular que sea relevante en opinión del investigador. 14. Estar participando o haber participado en otro ensayo clínico en los 2 meses previos a la inclusión. Paciente que ya ha participado en el ensayo SYL10101_IV. 15. Falta de cumplimiento tras el periodo de preinclusión. |
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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 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 | 12 |
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 | 1 |
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 |