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3-year Study in Dry Eye Disease Patients With Severe Keratitis Receiving Ikervis® (1mg/mL Ciclosporin)

Primary Purpose

Dry Eye Disease With Severe Keratitis

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Open-label Ikervis
Masked Ikervis
Vehicle Comparator: Masked Vehicle
Sponsored by
Santen SAS
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Dry Eye Disease With Severe Keratitis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. In the opinion of the investigator, the patient is capable of understanding and complying with protocol requirements.
  2. The patient has signed and dated a written informed consent form and any required privacy authorization prior to the initiation of any study procedures.
  3. Male or female patient is aged 18 years or above.
  4. At least 4 weeks of use of tear substitutes prior to the Baseline Visit
  5. DED patients with severe keratitis defined as the following:

    • CFS score of 3, 4 or 5 on the modified Oxford scale in at least one eye at Baseline Visits, AND
    • Schirmer test without anaesthesia scored <10 mm/5min in the same eye at Baseline Visit, AND
    • At least two moderate to very severe symptoms of dry eye disease with a score ≥2 (severity graded on a 0 to 4 grade scale), among the following symptoms: burning/stinging, foreign body sensation, eye dryness, eye pain and blurred/poor vision at Baseline Visit.
  6. Patient must be willing and able to undergo and return for scheduled study-related examinations.

Exclusion Criteria:

  1. Active herpes keratitis or history of ocular herpes.
  2. History of ocular trauma or ocular infection (viral, bacterial, fungal, protozoal) within 90 days before the Baseline Visit.
  3. Any ocular diseases other than DED requiring topical ocular treatment during the course of the study. Patients taking preservative-free IOP lowering medications are eligible for study enrolment.
  4. Concurrent ocular allergy (including seasonal conjunctivitis) or chronic conjunctivitis other than dry eye.
  5. Anticipated use of temporary punctal plugs during the study. Patients with punctal plugs placed prior to the Baseline Visit are eligible for enrolment; however, punctal plugs must remain in place during the study.
  6. Best corrected distance visual acuity (BCDVA) score ≤ 20/200 Snellen in each eye.
  7. Presence or history of any systemic or ocular disorder, condition or disease that could possibly interfere with the conduct of the required study procedures or the interpretation of study results or judged by the investigator to be incompatible with the study (e.g., diabetes with glycemia out of range, thyroid malfunction, uncontrolled autoimmune disease, current systemic infections, ocular infection…).
  8. Known hypersensitivity to one of the components of the study or procedural medications (e.g., fluorescein, etc.).
  9. History of ophthalmic malignancy
  10. History of malignancy (other than ophthalmic) in the last 5 years.
  11. Anticipated change during course of the study in the dose of systemic medications that could affect a dry eye condition [mainly, estrogen-progesterone or other estrogen derivatives (only allowed for post-menopausal women), pilocarpine, isotretinoine, tetracycline, antihistamines, tricyclic antidepressants, anxiolytics, antimuscarinics, beta-blocking agents, phenothiazines, omega-3, systemic corticosteroids]. These treatments are allowed during the study provided they remain stable throughout the course of the study.
  12. Use of topical ciclosporin in the past 3 months prior to Baseline visit.
  13. Any change in systemic immunosuppressant drugs within 30 days before the Baseline Visit or anticipated change during the course of the study.
  14. Pregnancy or lactation at the Baseline Visit.
  15. Women of childbearing potential not using a medically acceptable, highly effective method of birth control (such as hormonal implants, injectable or oral contraceptives together with condoms, some intrauterine devices, sexual abstinence or vasectomised partner) from the Baseline Visit throughout the conduct of the study treatment periods and up to 2 weeks after the study end. Post-menopausal women (two years without menstruation) do not need to use any method of birth control.
  16. Participation in a clinical trial with an investigational substance within the past 30 days prior to Baseline Visit.
  17. Participation in another clinical study at the same time as the present study.

Sites / Locations

  • Fakultní Nemocnice Brno
  • Fakultni Nemocnice Ostrava, Oční Klinika
  • University Hospital Hradec Kralove
  • Ocni klinika OFTEX
  • MEDOKO s.r.o.
  • Axon clinical s.r.o.
  • Masarykova nemocnice, Ocni oddeleni
  • Nemocnice Teplice, Ocni Oddeleni
  • Hospices Civils de Lyon - Hopital de la Croix-Rousse
  • Hopitaux Universitaires Paris-Sud - Hopital Bicetre
  • Hôpital des Quinze-Vingts
  • Hopitaux Universitaires Paris Nord Val de Seine - Hopital Bichat - Claude Bernard
  • Universita degli Studi di Milano - Clinica Oculistica I
  • Universita degli Studi di Milano - Ospedale San Giuseppe - Clinica Oculistica (University Eye Clinic)
  • ASST Santi Paolo e Carlo - Ospedale San Paolo Polo Universitario - Clinica Oculistica III
  • Polo Universita degli Studi di Milano - Ospedale Luigi Sacco - Clinica Oculistica (Eye Clinic)
  • Universita degli Studi di Pavia - Fondazione IRCCS Policlinico San Matteo - Clinica Oculistic
  • Azienda Ospedaliera Universitaria Policlinico Gaetano Martino - Messina
  • Universita degli Studi di Padova - Azienda Ospedaliera di Padova - Clinica Oculistica
  • Samodzielny Publiczny Szpital Kliniczny Nr 1 Klinika Diagnostyki i Mikrochirurgii Jaskry Oddział Okulistyki
  • Niepubliczny Zaklad Opieki Zdrowotnej Oko-Laser
  • Gabinet Okulistyczny Prof. Edward Wylęgała
  • Uniwersyteckie Centrum Kliniczne Śląskiego Uniwersytetu Medycznego w Katowicach
  • Retina Szpital Okulistyczny
  • Uniwersytecki Szpital Kiliniczny IM. Jana Milkulicza-Radeckiego we Wroclawiu
  • Federal State Institution Intersectoral Research and Technology Complex Eye microsurgery n.a. academician S.N. Fyodorov - Cheboksary
  • Ivanovo Regional Clinical Hospital
  • NMRC ISTC Eye Microsurgery n. a. Fyodorov - Moscow
  • State Budget Educational Institution of High Professional Education Moscow State Medical Stomatology University named after A.I.Evdokimov of MoH of RF
  • Saint Petersburg State Pediatric Medical University
  • First Saint Petersburg State Medical University named after academician I.P. Pavlov
  • FSBI The Academician S.N. Fyodorov IRTC Eye Microsurgery of the Minzdrava - Novosibirsk
  • GBOU VPO Omsk State Medical Academy, Ophthalmology Department
  • Saratov Railway Clinic
  • Cartujavision Oftalmologia
  • Hospital Clinico Universitario Lozano Blesa de Zaragoza
  • Institut Catala de Retina
  • Centro de Oftalmología Barraquer
  • Hospital Clinic de Barcelona (Hospital Clinic i Provincial)
  • Hospital Universitario Donostia, Oftalmalogia
  • Fundación Oftalmológica del Mediterráneo
  • Bayındır Kavaklidere Hospital Ophthalmology department
  • Ankara Üniversitesi Tıp Fakültesi Göz Hastalıkları Anabilim Dalı Vehbi Koç Göz Hastanesi
  • Ege Universitesi Tip Fakultesi Hastanesi Goz Hastaliklari Anabilim Dali
  • Selcuk University School of Medicine Ophthalmology department

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Other

Arm Label

Period 1 Open-label Ikervis

Period 2 Masked Ikervis

Period 2 Masked Vehicle

Arm Description

Period 1 for all patients: IKERVIS® (1mg/ml CsA). Instillation of one drop in each affected eye, once daily at bedtime. From Baseline for the first 12 months of treatment.

Period 2 for markedly improved patients at Month 12 only, and double-masked fashion. IKERVIS® (1mg/ml CsA). Instillation of one drop in each affected eye, once daily at bedtime. From Month 12 to Month 36.

Other: Vehicle Comparator. Period 2 for markedly improved patients at Month 12 only, and double-masked fashion. Vehicle. Instillation of one drop in each affected eye, once daily at bedtime. From Month 12 to Month 36.

Outcomes

Primary Outcome Measures

The correlation between mean change from baseline in CFS score and SANDE symptoms score at each visit.
CFS is corneal Fluorescein Staining, SANDE is Symptom Assessment iN Dry Eye
The cross correlation of sign at visit X versus symptoms at visit X+i (i starting from 0), if any.
The incident rate of ocular surface complications
Ocular surface complications are defined as corneal ulceration, corneal perforation, loss of visual acuity and ocular infection
The time to onset of ocular surface complications
Ocular surface complications are defined as corneal ulceration, corneal perforation, loss of visual acuity and ocular infection

Secondary Outcome Measures

Efficacy Secondary Outcome Measures in Period 1: CFS score at each visit in Period 1
Period 1 is Baseline to Month 12 included. CFS is Corneal Fluorescein Score. Staining using fluorescein (provided by the Sponsor) will be graded using the modified Oxford scale (7-point ordinal scale, score 0, 0.5, and 1 to 5 per area [cornea + nasal and temporal conjunctiva]) for cornea and conjunctiva separately. On this modified scale, the score 0 corresponds to no staining dots and the score 0.5 corresponds to one staining dot per area. A CFS grade of 0 represents complete corneal clearing.
Efficacy Secondary Outcome Measures in Period 1: Change from baseline in CFS score at each visit in Period 1
Period 1 is Baseline to Month 12 included. CFS is Corneal Fluorescein Score. Staining using fluorescein (provided by the Sponsor) will be graded using the modified Oxford scale (7-point ordinal scale, score 0, 0.5, and 1 to 5 per area [cornea + nasal and temporal conjunctiva]) for cornea and conjunctiva separately. On this modified scale, the score 0 corresponds to no staining dots and the score 0.5 corresponds to one staining dot per area. A CFS grade of 0 represents complete corneal clearing.
Efficacy Secondary Outcome Measures in Period 1: Conjunctival fluorescein staining score at each visit in Period 1
Period 1 is Baseline to Month 12 included. Staining using fluorescein (provided by the Sponsor) will be graded using the modified Oxford scale (7-point ordinal scale, score 0, 0.5, and 1 to 5 per area [cornea + nasal and temporal conjunctiva]) for cornea and conjunctiva separately. On this modified scale, the score 0 corresponds to no staining dots and the score 0.5 corresponds to one staining dot per area. A CFS grade of 0 represents complete corneal clearing.
Efficacy Secondary Outcome Measures in Period 1: Change from Baseline in Conjunctival fluorescein staining score at each visit in Period 1
Period 1 is Baseline to Month 12 included. Staining using fluorescein (provided by the Sponsor) will be graded using the modified Oxford scale (7-point ordinal scale, score 0, 0.5, and 1 to 5 per area [cornea + nasal and temporal conjunctiva]) for cornea and conjunctiva separately. On this modified scale, the score 0 corresponds to no staining dots and the score 0.5 corresponds to one staining dot per area. A CFS grade of 0 represents complete corneal clearing.
Efficacy Secondary Outcome Measures in Period 1: SANDE symptoms score at each visit in Period 1
Period 1 is Baseline to Month 12 included. SANDE is Symptom Assessment iN Dry Eye. The self-administered Symptom Assessment iN Dry Eye (SANDE) questionnaire must be completed by the patient him/herself. SANDE questionnaire will be used to score both severity and frequency of dry eye symptoms. This 2-item frequency- and severity-based visual analogue scales (0-100mm ranging respectively from" rarely" to "all the time", and from "very mild" to "very severe") is short and quick, and provides reliable measure for Dry Eye Disease symptoms assessment. Symptoms will be evaluated for both eyes together. A negative change from baseline (Period 1) or from Month 12 (Period 2) will indicate an improvement in dry eye disease symptoms.
Efficacy Secondary Outcome Measures in Period 1: Change from Baseline in SANDE symptoms score at each visit in Period 1
Period 1 is Baseline to Month 12 included. SANDE is Symptom Assessment iN Dry Eye. The self-administered Symptom Assessment iN Dry Eye (SANDE) questionnaire must be completed by the patient him/herself. SANDE questionnaire will be used to score both severity and frequency of dry eye symptoms. This 2-item frequency- and severity-based visual analogue scales (0-100mm ranging respectively from" rarely" to "all the time", and from "very mild" to "very severe") is short and quick, and provides reliable measure for Dry Eye Disease symptoms assessment. Symptoms will be evaluated for both eyes together. A negative change from baseline (Period 1) or from Month 12 (Period 2) will indicate an improvement in dry eye disease symptoms.
Efficacy Secondary Outcome Measures in Period 1: Symptoms score (5-point scale) at each visit, for each of the five symptoms assessed in Period 1
Period 1 is Baseline to Month 12 included.The 5-point Likert scales are a self-administered questionnaire and must be completed by the patient him/herself. Burning/stinging, foreign body sensation, eye dryness, photophobia, pain and blurred/poor vision, will be assessed by the study patients using a 5-point Likert scale from none to very severe (0 to 4). Symptoms will be evaluated for both eyes together.
Efficacy Secondary Outcome Measures in Period 1: Change from Baseline in Symptoms score (5-point scale) at each visit, for each of the five symptoms assessed in Period 1
Period 1 is Baseline to Month 12 included. The 5-point Likert scales are a self-administered questionnaire and must be completed by the patient him/herself. Burning/stinging, foreign body sensation, eye dryness, photophobia, pain and blurred/poor vision, will be assessed by the study patients using a 5-point Likert scale from none to very severe (0 to 4). Symptoms will be evaluated for both eyes together.
Efficacy Secondary Outcome Measures in Period 1: Occurrence of markedly improved in Period 1
Period 1 is Baseline to Month 12 included. Markedly improved is defined as CFS score improvement of 2 grades or more on the modified Oxford scale at Month 12.
Efficacy Secondary Outcome Measures in Period 1: time to become markedly improved in Period 1
Period 1 is Baseline to Month 12 included. Markedly improved is defined as CFS score improvement of 2 grades or more on the modified Oxford scale at Month 12.
Efficacy Secondary Outcome Measures in Period 1: TBUT at each visit in Period 1
Period 1 is Baseline to Month 12 included. TBUT is Tear Breakup Time. Tear break-up time (TBUT) will be measured by determining the time to tear break-up. The examiner will monitor the integrity of the tear film, noting the time it takes to form lacunae (clear spaces in the tear film) from the time that the eye is opened after the last blink. A higher value means longer time to tear break-up which is better. A positive change from baseline (Period 1) or from Month 12 (Period 2) will indicate improvement.
Efficacy Secondary Outcome Measures in Period 1: Change from Baseline in TBUT at each visit in Period 1
Period 1 is Baseline to Month 12 included. TBUT is Tear Breakup Time. Tear break-up time (TBUT) will be measured by determining the time to tear break-up. The examiner will monitor the integrity of the tear film, noting the time it takes to form lacunae (clear spaces in the tear film) from the time that the eye is opened after the last blink. A higher value means longer time to tear break-up which is better. A positive change from baseline (Period 1) or from Month 12 (Period 2) will indicate improvement.
Efficacy Secondary Outcome Measures in Period 1: Schirmer test at Month 12 visit
The rounded bent end of a sterile strip will be inserted into the lower conjunctival sac over the temporal one-third of the lower eyelid margin. After 5 minutes have elapsed the Schirmer test strip will be removed and the length of the tear absorption on the strip will be measured. A higher value means higher tear absorption which is better. A positive change from baseline (Period 1) or from Month 12 (Period 2) will indicate improvement.
Efficacy Secondary Outcome Measures in Period 1: Change from Baseline in Schirmer test at Month 12 visit
The rounded bent end of a sterile strip will be inserted into the lower conjunctival sac over the temporal one-third of the lower eyelid margin. After 5 minutes have elapsed the Schirmer test strip will be removed and the length of the tear absorption on the strip will be measured. A higher value means higher tear absorption which is better. A positive change from baseline (Period 1) or from Month 12 (Period 2) will indicate improvement.
Efficacy Secondary Outcome Measures in Period 1: Use of Artificial Tears over the last week at each visit in Period 1
Period 1 is Baseline to Month 12 included. The use of artificial tears will be monitored over the course of the study for each patient. Patients will be asked about the average number of times per day artificial tears was used over the last week, and number of days they were not used during the week preceding the visits.
Efficacy Secondary Outcome Measures in Period 1: Change from Baseline in Use of Artificial Tears over the last week at each visit in Period 1
Period 1 is Baseline to Month 12 included. The use of artificial tears will be monitored over the course of the study for each patient. Patients will be asked about the average number of times per day artificial tears was used over the last week, and number of days they were not used during the week preceding the visits.
Efficacy Secondary Outcome Measures in Period 2: CFS score at each visit in Period 2
Period 2 is Month 12 excluded to Month 36 included. CFS is Corneal Fluorescein Score. Staining using fluorescein (provided by the Sponsor) will be graded using the modified Oxford scale (7-point ordinal scale, score 0, 0.5, and 1 to 5 per area [cornea + nasal and temporal conjunctiva]) for cornea and conjunctiva separately. On this modified scale, the score 0 corresponds to no staining dots and the score 0.5 corresponds to one staining dot per area. A CFS grade of 0 represents complete corneal clearing.
Efficacy Secondary Outcome Measures in Period 2: Change from Month 12 visit in CFS score at each visit in Period 2
Period 2 is Month 12 excluded to Month 36 included. CFS is Corneal Fluorescein Score. Staining using fluorescein (provided by the Sponsor) will be graded using the modified Oxford scale (7-point ordinal scale, score 0, 0.5, and 1 to 5 per area [cornea + nasal and temporal conjunctiva]) for cornea and conjunctiva separately. On this modified scale, the score 0 corresponds to no staining dots and the score 0.5 corresponds to one staining dot per area. A CFS grade of 0 represents complete corneal clearing.
Efficacy Secondary Outcome Measures in Period 2: Conjunctival fluorescein staining score at each visit in Period 2
Period 2 is Month 12 excluded to Month 36 included. Staining using fluorescein (provided by the Sponsor) will be graded using the modified Oxford scale (7-point ordinal scale, score 0, 0.5, and 1 to 5 per area [cornea + nasal and temporal conjunctiva]) for cornea and conjunctiva separately. On this modified scale, the score 0 corresponds to no staining dots and the score 0.5 corresponds to one staining dot per area. A CFS grade of 0 represents complete corneal clearing.
Efficacy Secondary Outcome Measures in Period 2: Change from Month 12 visit in Conjunctival fluorescein staining score at each visit in Period 2
Period 2 is Month 12 excluded to Month 36 included. Staining using fluorescein (provided by the Sponsor) will be graded using the modified Oxford scale (7-point ordinal scale, score 0, 0.5, and 1 to 5 per area [cornea + nasal and temporal conjunctiva]) for cornea and conjunctiva separately. On this modified scale, the score 0 corresponds to no staining dots and the score 0.5 corresponds to one staining dot per area. A CFS grade of 0 represents complete corneal clearing.
Efficacy Secondary Outcome Measures in Period 2: SANDE symptoms score at each visit in Period 2
Period 2 is Month 12 excluded to Month 36 included. SANDE is Symptom Assessment iN Dry Eye. The self-administered Symptom Assessment iN Dry Eye (SANDE) questionnaire must be completed by the patient him/herself. SANDE questionnaire will be used to score both severity and frequency of dry eye symptoms. This 2-item frequency- and severity-based visual analogue scales (0-100mm ranging respectively from" rarely" to "all the time", and from "very mild" to "very severe") is short and quick, and provides reliable measure for Dry Eye Disease symptoms assessment. Symptoms will be evaluated for both eyes together. A negative change from baseline (Period 1) or from Month 12 (Period 2) will indicate an improvement in dry eye disease symptoms.
Efficacy Secondary Outcome Measures in Period 2: Change from Month 12 visit in SANDE symptoms score at each visit in Period 2
Period 2 is Month 12 excluded to Month 36 included. SANDE is Symptom Assessment iN Dry Eye. The self-administered Symptom Assessment iN Dry Eye (SANDE) questionnaire must be completed by the patient him/herself. SANDE questionnaire will be used to score both severity and frequency of dry eye symptoms. This 2-item frequency- and severity-based visual analogue scales (0-100mm ranging respectively from" rarely" to "all the time", and from "very mild" to "very severe") is short and quick, and provides reliable measure for Dry Eye Disease symptoms assessment. Symptoms will be evaluated for both eyes together. A negative change from baseline (Period 1) or from Month 12 (Period 2) will indicate an improvement in dry eye disease symptoms.
Efficacy Secondary Outcome Measures in Period 2: Symptoms score (5-point scale) at each visit, for each of the five symptoms assessed in Period 2
Period 2 is Month 12 excluded to Month 36 included. The 5-point Likert scales are a self-administered questionnaire and must be completed by the patient him/herself. Burning/stinging, foreign body sensation, eye dryness, photophobia, pain and blurred/poor vision, will be assessed by the study patients using a 5-point Likert scale from none to very severe (0 to 4). Symptoms will be evaluated for both eyes together.
Efficacy Secondary Outcome Measures in Period 2: Change from Month 12 visit in Symptoms score (5-point scale) at each visit, for each of the five symptoms assessed in Period 2
Period 2 is Month 12 excluded to Month 36 included. The 5-point Likert scales are a self-administered questionnaire and must be completed by the patient him/herself. Burning/stinging, foreign body sensation, eye dryness, photophobia, pain and blurred/poor vision, will be assessed by the study patients using a 5-point Likert scale from none to very severe (0 to 4). Symptoms will be evaluated for both eyes together.
Efficacy Secondary Outcome Measures in Period 2: TBUT at each visit in Period 2
Period 2 is Month 12 excluded to Month 36 included. TBUT is Tear Breakup Time. Tear break-up time (TBUT) will be measured by determining the time to tear break-up. The examiner will monitor the integrity of the tear film, noting the time it takes to form lacunae (clear spaces in the tear film) from the time that the eye is opened after the last blink. A higher value means longer time to tear break-up which is better. A positive change from baseline (Period 1) or from Month 12 (Period 2) will indicate improvement.
Efficacy Secondary Outcome Measures in Period 2: Change from Month 12 visit in TBUT at each visit in Period 2
Period 2 is Month 12 excluded to Month 36 included. TBUT is Tear Breakup Time. Tear break-up time (TBUT) will be measured by determining the time to tear break-up. The examiner will monitor the integrity of the tear film, noting the time it takes to form lacunae (clear spaces in the tear film) from the time that the eye is opened after the last blink. A higher value means longer time to tear break-up which is better. A positive change from baseline (Period 1) or from Month 12 (Period 2) will indicate improvement.
Efficacy Secondary Outcome Measures in Period 2: Schirmer test at Month 24 and Month 36 visits
The rounded bent end of a sterile strip will be inserted into the lower conjunctival sac over the temporal one-third of the lower eyelid margin. After 5 minutes have elapsed the Schirmer test strip will be removed and the length of the tear absorption on the strip will be measured. A higher value means higher tear absorption which is better. A positive change from baseline (Period 1) or from Month 12 (Period 2) will indicate improvement.
Efficacy Secondary Outcome Measures in Period 2: Change from Month 12 visit in Schirmer test at Month 24 and Month 36 visits
The rounded bent end of a sterile strip will be inserted into the lower conjunctival sac over the temporal one-third of the lower eyelid margin. After 5 minutes have elapsed the Schirmer test strip will be removed and the length of the tear absorption on the strip will be measured. A higher value means higher tear absorption which is better. A positive change from baseline (Period 1) or from Month 12 (Period 2) will indicate improvement.
Efficacy Secondary Outcome Measures in Period 2: Use of Artificial Tears over the last week, at each visit in Period 2
Period 2 is Month 12 excluded to Month 36 included. The use of artificial tears will be monitored over the course of the study for each patient. Patients will be asked about the average number of times per day artificial tears was used over the last week, and number of days they were not used during the week preceding the visits.
Efficacy Secondary Outcome Measures in Period 2: Change from Month 12 visit in Use of Artificial Tears over the last week, at each visit in Period 2
Period 2 is Month 12 excluded to Month 36 included. The use of artificial tears will be monitored over the course of the study for each patient. Patients will be asked about the average number of times per day artificial tears was used over the last week, and number of days they were not used during the week preceding the visits.
Efficacy Secondary Outcome Measures in Period 2: Occurrence of relapse in Period 2
Period 2 is Month 12 excluded to Month 36 included. Relapse is defined as an increase of CFS score of 2 or more on the modified Oxford scale
Efficacy Secondary Outcome Measures in Period 2: time to relapse in Period 2
Period 2 is Month 12 excluded to Month 36 included. Relapse is defined as an increase of CFS score of 2 or more on the modified Oxford scale
Efficacy Secondary Outcome Measures in Entire study: CFS score at each visit in Entire study
CFS is Corneal Fluorescein Score. Staining using fluorescein (provided by the Sponsor) will be graded using the modified Oxford scale (7-point ordinal scale, score 0, 0.5, and 1 to 5 per area [cornea + nasal and temporal conjunctiva]) for cornea and conjunctiva separately. On this modified scale, the score 0 corresponds to no staining dots and the score 0.5 corresponds to one staining dot per area. A CFS grade of 0 represents complete corneal clearing.
Efficacy Secondary Outcome Measures in Entire study: Change from baseline in CFS score at each visit in Entire study
CFS is Corneal Fluorescein Score. Staining using fluorescein (provided by the Sponsor) will be graded using the modified Oxford scale (7-point ordinal scale, score 0, 0.5, and 1 to 5 per area [cornea + nasal and temporal conjunctiva]) for cornea and conjunctiva separately. On this modified scale, the score 0 corresponds to no staining dots and the score 0.5 corresponds to one staining dot per area. A CFS grade of 0 represents complete corneal clearing.
Efficacy Secondary Outcome Measures in Entire study: Conjunctival fluorescein staining score at each visit in Entire study
Staining using fluorescein (provided by the Sponsor) will be graded using the modified Oxford scale (7-point ordinal scale, score 0, 0.5, and 1 to 5 per area [cornea + nasal and temporal conjunctiva]) for cornea and conjunctiva separately. On this modified scale, the score 0 corresponds to no staining dots and the score 0.5 corresponds to one staining dot per area. A CFS grade of 0 represents complete corneal clearing.
Efficacy Secondary Outcome Measures in Entire study: Change from Baseline in Conjunctival fluorescein staining score at each visit in Entire study
Staining using fluorescein (provided by the Sponsor) will be graded using the modified Oxford scale (7-point ordinal scale, score 0, 0.5, and 1 to 5 per area [cornea + nasal and temporal conjunctiva]) for cornea and conjunctiva separately. On this modified scale, the score 0 corresponds to no staining dots and the score 0.5 corresponds to one staining dot per area. A CFS grade of 0 represents complete corneal clearing.
Efficacy Secondary Outcome Measures in Entire study: SANDE symptoms score at each visit in Entire study
SANDE is Symptom Assessment iN Dry Eye. The self-administered Symptom Assessment iN Dry Eye (SANDE) questionnaire must be completed by the patient him/herself. SANDE questionnaire will be used to score both severity and frequency of dry eye symptoms. This 2-item frequency- and severity-based visual analogue scales (0-100mm ranging respectively from" rarely" to "all the time", and from "very mild" to "very severe") is short and quick, and provides reliable measure for Dry Eye Disease symptoms assessment. Symptoms will be evaluated for both eyes together. A negative change from baseline (Period 1) or from Month 12 (Period 2) will indicate an improvement in dry eye disease symptoms.
Efficacy Secondary Outcome Measures in Entire study: Change from Baseline in SANDE symptoms score at each visit in Entire study
SANDE is Symptom Assessment iN Dry Eye. The self-administered Symptom Assessment iN Dry Eye (SANDE) questionnaire must be completed by the patient him/herself. SANDE questionnaire will be used to score both severity and frequency of dry eye symptoms. This 2-item frequency- and severity-based visual analogue scales (0-100mm ranging respectively from" rarely" to "all the time", and from "very mild" to "very severe") is short and quick, and provides reliable measure for Dry Eye Disease symptoms assessment. Symptoms will be evaluated for both eyes together. A negative change from baseline (Period 1) or from Month 12 (Period 2) will indicate an improvement in dry eye disease symptoms.
Efficacy Secondary Outcome Measures in Entire study: Symptoms score (5-point scale) at each visit, for each of the five symptoms assessed in Entire study
The 5-point Likert scales are a self-administered questionnaire and must be completed by the patient him/herself. Burning/stinging, foreign body sensation, eye dryness, photophobia, pain and blurred/poor vision, will be assessed by the study patients using a 5-point Likert scale from none to very severe (0 to 4). Symptoms will be evaluated for both eyes together.
Efficacy Secondary Outcome Measures in Entire study: Change from Baseline in Symptoms score (5-point scale) at each visit, for each of the five symptoms assessed in Entire study
The 5-point Likert scales are a self-administered questionnaire and must be completed by the patient him/herself. Burning/stinging, foreign body sensation, eye dryness, photophobia, pain and blurred/poor vision, will be assessed by the study patients using a 5-point Likert scale from none to very severe (0 to 4). Symptoms will be evaluated for both eyes together.
Efficacy Secondary Outcome Measures in Entire study: TBUT at each visit in Entire study
TBUT is Tear Breakup Time. Tear break-up time (TBUT) will be measured by determining the time to tear break-up. The examiner will monitor the integrity of the tear film, noting the time it takes to form lacunae (clear spaces in the tear film) from the time that the eye is opened after the last blink. A higher value means longer time to tear break-up which is better. A positive change from baseline (Period 1) or from Month 12 (Period 2) will indicate improvement.
Efficacy Secondary Outcome Measures in Entire study: Change from Baseline in TBUT at each visit in Entire study
TBUT is Tear Breakup Time. Tear break-up time (TBUT) will be measured by determining the time to tear break-up. The examiner will monitor the integrity of the tear film, noting the time it takes to form lacunae (clear spaces in the tear film) from the time that the eye is opened after the last blink. A higher value means longer time to tear break-up which is better. A positive change from baseline (Period 1) or from Month 12 (Period 2) will indicate improvement.
Efficacy Secondary Outcome Measures in Entire study: Schirmer test at Month 12, Month 24 and Month 36 visits
The rounded bent end of a sterile strip will be inserted into the lower conjunctival sac over the temporal one-third of the lower eyelid margin. After 5 minutes have elapsed the Schirmer test strip will be removed and the length of the tear absorption on the strip will be measured. A higher value means higher tear absorption which is better. A positive change from baseline (Period 1) or from Month 12 (Period 2) will indicate improvement.
Efficacy Secondary Outcome Measures in Entire study: Change from Baseline in Schirmer test at Month 12, Month 24 and Month 36 visits
The rounded bent end of a sterile strip will be inserted into the lower conjunctival sac over the temporal one-third of the lower eyelid margin. After 5 minutes have elapsed the Schirmer test strip will be removed and the length of the tear absorption on the strip will be measured. A higher value means higher tear absorption which is better. A positive change from baseline (Period 1) or from Month 12 (Period 2) will indicate improvement.
Efficacy Secondary Outcome Measures in Entire study: Use of Artificial Tears over the last week at each visit in Entire study
The use of artificial tears will be monitored over the course of the study for each patient. Patients will be asked about the average number of times per day artificial tears was used over the last week, and number of days they were not used during the week preceding the visits.
Efficacy Secondary Outcome Measures in Entire study: Change from Baseline in Use of Artificial Tears over the last week at each visit in Entire study
The use of artificial tears will be monitored over the course of the study for each patient. Patients will be asked about the average number of times per day artificial tears was used over the last week, and number of days they were not used during the week preceding the visits.
Quality of Life Outcome: DEQS overall score at Month 6, Month 12, Month 18, Month 24, Month 30 and Month 36 Visits.
DEQS is Dry Eye related Quality of life Score. The DEQS consists of 15 items related to dry eye symptoms and influence on daily life, and the overall degree of Quality of Life impairment is calculated as a summary score (0 to 100), lower score meaning better.
Quality of Life Outcome: Change from Baseline in DEQS at Month 6, Month 12, Month 18, Month 24, Month 30 and Month 36 Visits. Change from Month 12 will also be summarized for scores collected in Period 2.
DEQS is Dry Eye related Quality of life Score. The DEQS consists of 15 items related to dry eye symptoms and influence on daily life, and the overall degree of Quality of Life impairment is calculated as a summary score (0 to 100), lower score meaning better.
Safety and Tolerability Outcome: IOP at Month 12, Month 24 and Month 36 visits
IOP is Intraocular pressure
Safety and Tolerability Outcome: Change from Baseline in IOP at Month 12, Month 24 and Month 36 visits
IOP is Intraocular pressure
Safety and Tolerability Outcome: BCDVA at Month 6, Month 12, Month 24 and Month 36 visits
BCDVA is Best Corrected Distance Visual Acuity. Lowest visual acuity corresponds to Snellen value 20/200, while best visual acuity corresponds to Snellen value 20/20 or higher.
Safety and Tolerability Outcome: Change from Baseline in BCDVA at Month 6, Month 12, Month 24 and Month 36 visits
BCDVA is Best Corrected Distance Visual Acuity. Lowest visual acuity corresponds to Snellen value 20/200, while best visual acuity corresponds to Snellen value 20/20 or higher.
Safety and Tolerability Outcome: Incidence of ocular and systemic AEs over the three-year study period.
AE is Adverse Event
Safety and Tolerability Outcome: Severity of ocular and systemic AEs over the three-year study period.
AE is Adverse Event

Full Information

First Posted
October 25, 2019
Last Updated
October 11, 2023
Sponsor
Santen SAS
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1. Study Identification

Unique Protocol Identification Number
NCT04144413
Brief Title
3-year Study in Dry Eye Disease Patients With Severe Keratitis Receiving Ikervis® (1mg/mL Ciclosporin)
Official Title
A Phase IIIb, Prospective, Interventional, Multicentre, 3-year Study to Explore the Long-term Evolution of Sign and Symptoms, and Occurence of Complications in Dry Eye Patients With Severe Keratitis Receiving Ikervis® (1mg/mL Ciclosporin)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Completed
Study Start Date
May 31, 2019 (Actual)
Primary Completion Date
July 14, 2023 (Actual)
Study Completion Date
July 14, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Santen SAS

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The proposed 36-month Post Approval Efficacy Study (PAES) is a prospective, interventional, multicentre study to explore the long-term evolution of signs and symptoms, and occurrence of complications in Dry Eye Disease (DED) patients with severe keratitis receiving Ikervis® (1mg/mL ciclosporin) eye drops administered once daily

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dry Eye Disease With Severe Keratitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
In order to assess the response to IKERVIS® for DED patients with severe keratitis, after 12-month IKERVIS® (once daily) treatment, patients who have shown a marked improvement at Month 12 (as defined below) will be randomised to receive IKERVIS® or Vehicle (ration 3:2) in double-masked fashion.
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
350 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Period 1 Open-label Ikervis
Arm Type
Experimental
Arm Description
Period 1 for all patients: IKERVIS® (1mg/ml CsA). Instillation of one drop in each affected eye, once daily at bedtime. From Baseline for the first 12 months of treatment.
Arm Title
Period 2 Masked Ikervis
Arm Type
Experimental
Arm Description
Period 2 for markedly improved patients at Month 12 only, and double-masked fashion. IKERVIS® (1mg/ml CsA). Instillation of one drop in each affected eye, once daily at bedtime. From Month 12 to Month 36.
Arm Title
Period 2 Masked Vehicle
Arm Type
Other
Arm Description
Other: Vehicle Comparator. Period 2 for markedly improved patients at Month 12 only, and double-masked fashion. Vehicle. Instillation of one drop in each affected eye, once daily at bedtime. From Month 12 to Month 36.
Intervention Type
Drug
Intervention Name(s)
Open-label Ikervis
Intervention Description
NOVA22007, IKERVIS® is a sterile, ophthalmic cationic oil-in-water emulsion containing 1mg/ml CsA.
Intervention Type
Drug
Intervention Name(s)
Masked Ikervis
Intervention Description
NOVA22007, IKERVIS® is a sterile, ophthalmic cationic oil-in-water emulsion containing 1mg/ml CsA.
Intervention Type
Other
Intervention Name(s)
Vehicle Comparator: Masked Vehicle
Intervention Description
Vehicle of IKERVIS® - sterile, ophthalmic cationic oil-in-water emulsion containing no active substance.
Primary Outcome Measure Information:
Title
The correlation between mean change from baseline in CFS score and SANDE symptoms score at each visit.
Description
CFS is corneal Fluorescein Staining, SANDE is Symptom Assessment iN Dry Eye
Time Frame
36 months
Title
The cross correlation of sign at visit X versus symptoms at visit X+i (i starting from 0), if any.
Time Frame
36 months
Title
The incident rate of ocular surface complications
Description
Ocular surface complications are defined as corneal ulceration, corneal perforation, loss of visual acuity and ocular infection
Time Frame
36 months
Title
The time to onset of ocular surface complications
Description
Ocular surface complications are defined as corneal ulceration, corneal perforation, loss of visual acuity and ocular infection
Time Frame
36 months
Secondary Outcome Measure Information:
Title
Efficacy Secondary Outcome Measures in Period 1: CFS score at each visit in Period 1
Description
Period 1 is Baseline to Month 12 included. CFS is Corneal Fluorescein Score. Staining using fluorescein (provided by the Sponsor) will be graded using the modified Oxford scale (7-point ordinal scale, score 0, 0.5, and 1 to 5 per area [cornea + nasal and temporal conjunctiva]) for cornea and conjunctiva separately. On this modified scale, the score 0 corresponds to no staining dots and the score 0.5 corresponds to one staining dot per area. A CFS grade of 0 represents complete corneal clearing.
Time Frame
12 months (Period 1)
Title
Efficacy Secondary Outcome Measures in Period 1: Change from baseline in CFS score at each visit in Period 1
Description
Period 1 is Baseline to Month 12 included. CFS is Corneal Fluorescein Score. Staining using fluorescein (provided by the Sponsor) will be graded using the modified Oxford scale (7-point ordinal scale, score 0, 0.5, and 1 to 5 per area [cornea + nasal and temporal conjunctiva]) for cornea and conjunctiva separately. On this modified scale, the score 0 corresponds to no staining dots and the score 0.5 corresponds to one staining dot per area. A CFS grade of 0 represents complete corneal clearing.
Time Frame
12 months (Period 1)
Title
Efficacy Secondary Outcome Measures in Period 1: Conjunctival fluorescein staining score at each visit in Period 1
Description
Period 1 is Baseline to Month 12 included. Staining using fluorescein (provided by the Sponsor) will be graded using the modified Oxford scale (7-point ordinal scale, score 0, 0.5, and 1 to 5 per area [cornea + nasal and temporal conjunctiva]) for cornea and conjunctiva separately. On this modified scale, the score 0 corresponds to no staining dots and the score 0.5 corresponds to one staining dot per area. A CFS grade of 0 represents complete corneal clearing.
Time Frame
12 months (Period 1)
Title
Efficacy Secondary Outcome Measures in Period 1: Change from Baseline in Conjunctival fluorescein staining score at each visit in Period 1
Description
Period 1 is Baseline to Month 12 included. Staining using fluorescein (provided by the Sponsor) will be graded using the modified Oxford scale (7-point ordinal scale, score 0, 0.5, and 1 to 5 per area [cornea + nasal and temporal conjunctiva]) for cornea and conjunctiva separately. On this modified scale, the score 0 corresponds to no staining dots and the score 0.5 corresponds to one staining dot per area. A CFS grade of 0 represents complete corneal clearing.
Time Frame
12 months (Period 1)
Title
Efficacy Secondary Outcome Measures in Period 1: SANDE symptoms score at each visit in Period 1
Description
Period 1 is Baseline to Month 12 included. SANDE is Symptom Assessment iN Dry Eye. The self-administered Symptom Assessment iN Dry Eye (SANDE) questionnaire must be completed by the patient him/herself. SANDE questionnaire will be used to score both severity and frequency of dry eye symptoms. This 2-item frequency- and severity-based visual analogue scales (0-100mm ranging respectively from" rarely" to "all the time", and from "very mild" to "very severe") is short and quick, and provides reliable measure for Dry Eye Disease symptoms assessment. Symptoms will be evaluated for both eyes together. A negative change from baseline (Period 1) or from Month 12 (Period 2) will indicate an improvement in dry eye disease symptoms.
Time Frame
12 months (Period 1)
Title
Efficacy Secondary Outcome Measures in Period 1: Change from Baseline in SANDE symptoms score at each visit in Period 1
Description
Period 1 is Baseline to Month 12 included. SANDE is Symptom Assessment iN Dry Eye. The self-administered Symptom Assessment iN Dry Eye (SANDE) questionnaire must be completed by the patient him/herself. SANDE questionnaire will be used to score both severity and frequency of dry eye symptoms. This 2-item frequency- and severity-based visual analogue scales (0-100mm ranging respectively from" rarely" to "all the time", and from "very mild" to "very severe") is short and quick, and provides reliable measure for Dry Eye Disease symptoms assessment. Symptoms will be evaluated for both eyes together. A negative change from baseline (Period 1) or from Month 12 (Period 2) will indicate an improvement in dry eye disease symptoms.
Time Frame
12 months (Period 1)
Title
Efficacy Secondary Outcome Measures in Period 1: Symptoms score (5-point scale) at each visit, for each of the five symptoms assessed in Period 1
Description
Period 1 is Baseline to Month 12 included.The 5-point Likert scales are a self-administered questionnaire and must be completed by the patient him/herself. Burning/stinging, foreign body sensation, eye dryness, photophobia, pain and blurred/poor vision, will be assessed by the study patients using a 5-point Likert scale from none to very severe (0 to 4). Symptoms will be evaluated for both eyes together.
Time Frame
12 months (Period 1)
Title
Efficacy Secondary Outcome Measures in Period 1: Change from Baseline in Symptoms score (5-point scale) at each visit, for each of the five symptoms assessed in Period 1
Description
Period 1 is Baseline to Month 12 included. The 5-point Likert scales are a self-administered questionnaire and must be completed by the patient him/herself. Burning/stinging, foreign body sensation, eye dryness, photophobia, pain and blurred/poor vision, will be assessed by the study patients using a 5-point Likert scale from none to very severe (0 to 4). Symptoms will be evaluated for both eyes together.
Time Frame
12 months (Period 1)
Title
Efficacy Secondary Outcome Measures in Period 1: Occurrence of markedly improved in Period 1
Description
Period 1 is Baseline to Month 12 included. Markedly improved is defined as CFS score improvement of 2 grades or more on the modified Oxford scale at Month 12.
Time Frame
12 months (Period 1)
Title
Efficacy Secondary Outcome Measures in Period 1: time to become markedly improved in Period 1
Description
Period 1 is Baseline to Month 12 included. Markedly improved is defined as CFS score improvement of 2 grades or more on the modified Oxford scale at Month 12.
Time Frame
12 months (Period 1)
Title
Efficacy Secondary Outcome Measures in Period 1: TBUT at each visit in Period 1
Description
Period 1 is Baseline to Month 12 included. TBUT is Tear Breakup Time. Tear break-up time (TBUT) will be measured by determining the time to tear break-up. The examiner will monitor the integrity of the tear film, noting the time it takes to form lacunae (clear spaces in the tear film) from the time that the eye is opened after the last blink. A higher value means longer time to tear break-up which is better. A positive change from baseline (Period 1) or from Month 12 (Period 2) will indicate improvement.
Time Frame
12 months (Period 1)
Title
Efficacy Secondary Outcome Measures in Period 1: Change from Baseline in TBUT at each visit in Period 1
Description
Period 1 is Baseline to Month 12 included. TBUT is Tear Breakup Time. Tear break-up time (TBUT) will be measured by determining the time to tear break-up. The examiner will monitor the integrity of the tear film, noting the time it takes to form lacunae (clear spaces in the tear film) from the time that the eye is opened after the last blink. A higher value means longer time to tear break-up which is better. A positive change from baseline (Period 1) or from Month 12 (Period 2) will indicate improvement.
Time Frame
12 months (Period 1)
Title
Efficacy Secondary Outcome Measures in Period 1: Schirmer test at Month 12 visit
Description
The rounded bent end of a sterile strip will be inserted into the lower conjunctival sac over the temporal one-third of the lower eyelid margin. After 5 minutes have elapsed the Schirmer test strip will be removed and the length of the tear absorption on the strip will be measured. A higher value means higher tear absorption which is better. A positive change from baseline (Period 1) or from Month 12 (Period 2) will indicate improvement.
Time Frame
visit Month 12
Title
Efficacy Secondary Outcome Measures in Period 1: Change from Baseline in Schirmer test at Month 12 visit
Description
The rounded bent end of a sterile strip will be inserted into the lower conjunctival sac over the temporal one-third of the lower eyelid margin. After 5 minutes have elapsed the Schirmer test strip will be removed and the length of the tear absorption on the strip will be measured. A higher value means higher tear absorption which is better. A positive change from baseline (Period 1) or from Month 12 (Period 2) will indicate improvement.
Time Frame
visit Month 12
Title
Efficacy Secondary Outcome Measures in Period 1: Use of Artificial Tears over the last week at each visit in Period 1
Description
Period 1 is Baseline to Month 12 included. The use of artificial tears will be monitored over the course of the study for each patient. Patients will be asked about the average number of times per day artificial tears was used over the last week, and number of days they were not used during the week preceding the visits.
Time Frame
12 months (Period 1)
Title
Efficacy Secondary Outcome Measures in Period 1: Change from Baseline in Use of Artificial Tears over the last week at each visit in Period 1
Description
Period 1 is Baseline to Month 12 included. The use of artificial tears will be monitored over the course of the study for each patient. Patients will be asked about the average number of times per day artificial tears was used over the last week, and number of days they were not used during the week preceding the visits.
Time Frame
12 months (Period 1)
Title
Efficacy Secondary Outcome Measures in Period 2: CFS score at each visit in Period 2
Description
Period 2 is Month 12 excluded to Month 36 included. CFS is Corneal Fluorescein Score. Staining using fluorescein (provided by the Sponsor) will be graded using the modified Oxford scale (7-point ordinal scale, score 0, 0.5, and 1 to 5 per area [cornea + nasal and temporal conjunctiva]) for cornea and conjunctiva separately. On this modified scale, the score 0 corresponds to no staining dots and the score 0.5 corresponds to one staining dot per area. A CFS grade of 0 represents complete corneal clearing.
Time Frame
24 months (Period 2)
Title
Efficacy Secondary Outcome Measures in Period 2: Change from Month 12 visit in CFS score at each visit in Period 2
Description
Period 2 is Month 12 excluded to Month 36 included. CFS is Corneal Fluorescein Score. Staining using fluorescein (provided by the Sponsor) will be graded using the modified Oxford scale (7-point ordinal scale, score 0, 0.5, and 1 to 5 per area [cornea + nasal and temporal conjunctiva]) for cornea and conjunctiva separately. On this modified scale, the score 0 corresponds to no staining dots and the score 0.5 corresponds to one staining dot per area. A CFS grade of 0 represents complete corneal clearing.
Time Frame
24 months (Period 2)
Title
Efficacy Secondary Outcome Measures in Period 2: Conjunctival fluorescein staining score at each visit in Period 2
Description
Period 2 is Month 12 excluded to Month 36 included. Staining using fluorescein (provided by the Sponsor) will be graded using the modified Oxford scale (7-point ordinal scale, score 0, 0.5, and 1 to 5 per area [cornea + nasal and temporal conjunctiva]) for cornea and conjunctiva separately. On this modified scale, the score 0 corresponds to no staining dots and the score 0.5 corresponds to one staining dot per area. A CFS grade of 0 represents complete corneal clearing.
Time Frame
24 months (Period 2)
Title
Efficacy Secondary Outcome Measures in Period 2: Change from Month 12 visit in Conjunctival fluorescein staining score at each visit in Period 2
Description
Period 2 is Month 12 excluded to Month 36 included. Staining using fluorescein (provided by the Sponsor) will be graded using the modified Oxford scale (7-point ordinal scale, score 0, 0.5, and 1 to 5 per area [cornea + nasal and temporal conjunctiva]) for cornea and conjunctiva separately. On this modified scale, the score 0 corresponds to no staining dots and the score 0.5 corresponds to one staining dot per area. A CFS grade of 0 represents complete corneal clearing.
Time Frame
24 months (Period 2)
Title
Efficacy Secondary Outcome Measures in Period 2: SANDE symptoms score at each visit in Period 2
Description
Period 2 is Month 12 excluded to Month 36 included. SANDE is Symptom Assessment iN Dry Eye. The self-administered Symptom Assessment iN Dry Eye (SANDE) questionnaire must be completed by the patient him/herself. SANDE questionnaire will be used to score both severity and frequency of dry eye symptoms. This 2-item frequency- and severity-based visual analogue scales (0-100mm ranging respectively from" rarely" to "all the time", and from "very mild" to "very severe") is short and quick, and provides reliable measure for Dry Eye Disease symptoms assessment. Symptoms will be evaluated for both eyes together. A negative change from baseline (Period 1) or from Month 12 (Period 2) will indicate an improvement in dry eye disease symptoms.
Time Frame
24 months (Period 2)
Title
Efficacy Secondary Outcome Measures in Period 2: Change from Month 12 visit in SANDE symptoms score at each visit in Period 2
Description
Period 2 is Month 12 excluded to Month 36 included. SANDE is Symptom Assessment iN Dry Eye. The self-administered Symptom Assessment iN Dry Eye (SANDE) questionnaire must be completed by the patient him/herself. SANDE questionnaire will be used to score both severity and frequency of dry eye symptoms. This 2-item frequency- and severity-based visual analogue scales (0-100mm ranging respectively from" rarely" to "all the time", and from "very mild" to "very severe") is short and quick, and provides reliable measure for Dry Eye Disease symptoms assessment. Symptoms will be evaluated for both eyes together. A negative change from baseline (Period 1) or from Month 12 (Period 2) will indicate an improvement in dry eye disease symptoms.
Time Frame
24 months (Period 2)
Title
Efficacy Secondary Outcome Measures in Period 2: Symptoms score (5-point scale) at each visit, for each of the five symptoms assessed in Period 2
Description
Period 2 is Month 12 excluded to Month 36 included. The 5-point Likert scales are a self-administered questionnaire and must be completed by the patient him/herself. Burning/stinging, foreign body sensation, eye dryness, photophobia, pain and blurred/poor vision, will be assessed by the study patients using a 5-point Likert scale from none to very severe (0 to 4). Symptoms will be evaluated for both eyes together.
Time Frame
24 months (Period 2)
Title
Efficacy Secondary Outcome Measures in Period 2: Change from Month 12 visit in Symptoms score (5-point scale) at each visit, for each of the five symptoms assessed in Period 2
Description
Period 2 is Month 12 excluded to Month 36 included. The 5-point Likert scales are a self-administered questionnaire and must be completed by the patient him/herself. Burning/stinging, foreign body sensation, eye dryness, photophobia, pain and blurred/poor vision, will be assessed by the study patients using a 5-point Likert scale from none to very severe (0 to 4). Symptoms will be evaluated for both eyes together.
Time Frame
24 months (Period 2)
Title
Efficacy Secondary Outcome Measures in Period 2: TBUT at each visit in Period 2
Description
Period 2 is Month 12 excluded to Month 36 included. TBUT is Tear Breakup Time. Tear break-up time (TBUT) will be measured by determining the time to tear break-up. The examiner will monitor the integrity of the tear film, noting the time it takes to form lacunae (clear spaces in the tear film) from the time that the eye is opened after the last blink. A higher value means longer time to tear break-up which is better. A positive change from baseline (Period 1) or from Month 12 (Period 2) will indicate improvement.
Time Frame
24 months (Period 2)
Title
Efficacy Secondary Outcome Measures in Period 2: Change from Month 12 visit in TBUT at each visit in Period 2
Description
Period 2 is Month 12 excluded to Month 36 included. TBUT is Tear Breakup Time. Tear break-up time (TBUT) will be measured by determining the time to tear break-up. The examiner will monitor the integrity of the tear film, noting the time it takes to form lacunae (clear spaces in the tear film) from the time that the eye is opened after the last blink. A higher value means longer time to tear break-up which is better. A positive change from baseline (Period 1) or from Month 12 (Period 2) will indicate improvement.
Time Frame
24 months (Period 2)
Title
Efficacy Secondary Outcome Measures in Period 2: Schirmer test at Month 24 and Month 36 visits
Description
The rounded bent end of a sterile strip will be inserted into the lower conjunctival sac over the temporal one-third of the lower eyelid margin. After 5 minutes have elapsed the Schirmer test strip will be removed and the length of the tear absorption on the strip will be measured. A higher value means higher tear absorption which is better. A positive change from baseline (Period 1) or from Month 12 (Period 2) will indicate improvement.
Time Frame
Month 24 and Month 36 visits
Title
Efficacy Secondary Outcome Measures in Period 2: Change from Month 12 visit in Schirmer test at Month 24 and Month 36 visits
Description
The rounded bent end of a sterile strip will be inserted into the lower conjunctival sac over the temporal one-third of the lower eyelid margin. After 5 minutes have elapsed the Schirmer test strip will be removed and the length of the tear absorption on the strip will be measured. A higher value means higher tear absorption which is better. A positive change from baseline (Period 1) or from Month 12 (Period 2) will indicate improvement.
Time Frame
Month 24 and Month 36 visits
Title
Efficacy Secondary Outcome Measures in Period 2: Use of Artificial Tears over the last week, at each visit in Period 2
Description
Period 2 is Month 12 excluded to Month 36 included. The use of artificial tears will be monitored over the course of the study for each patient. Patients will be asked about the average number of times per day artificial tears was used over the last week, and number of days they were not used during the week preceding the visits.
Time Frame
24 months (Period 2)
Title
Efficacy Secondary Outcome Measures in Period 2: Change from Month 12 visit in Use of Artificial Tears over the last week, at each visit in Period 2
Description
Period 2 is Month 12 excluded to Month 36 included. The use of artificial tears will be monitored over the course of the study for each patient. Patients will be asked about the average number of times per day artificial tears was used over the last week, and number of days they were not used during the week preceding the visits.
Time Frame
24 months (Period 2)
Title
Efficacy Secondary Outcome Measures in Period 2: Occurrence of relapse in Period 2
Description
Period 2 is Month 12 excluded to Month 36 included. Relapse is defined as an increase of CFS score of 2 or more on the modified Oxford scale
Time Frame
24 months (Period 2)
Title
Efficacy Secondary Outcome Measures in Period 2: time to relapse in Period 2
Description
Period 2 is Month 12 excluded to Month 36 included. Relapse is defined as an increase of CFS score of 2 or more on the modified Oxford scale
Time Frame
24 months (Period 2)
Title
Efficacy Secondary Outcome Measures in Entire study: CFS score at each visit in Entire study
Description
CFS is Corneal Fluorescein Score. Staining using fluorescein (provided by the Sponsor) will be graded using the modified Oxford scale (7-point ordinal scale, score 0, 0.5, and 1 to 5 per area [cornea + nasal and temporal conjunctiva]) for cornea and conjunctiva separately. On this modified scale, the score 0 corresponds to no staining dots and the score 0.5 corresponds to one staining dot per area. A CFS grade of 0 represents complete corneal clearing.
Time Frame
36 months (Periods 1 + 2)
Title
Efficacy Secondary Outcome Measures in Entire study: Change from baseline in CFS score at each visit in Entire study
Description
CFS is Corneal Fluorescein Score. Staining using fluorescein (provided by the Sponsor) will be graded using the modified Oxford scale (7-point ordinal scale, score 0, 0.5, and 1 to 5 per area [cornea + nasal and temporal conjunctiva]) for cornea and conjunctiva separately. On this modified scale, the score 0 corresponds to no staining dots and the score 0.5 corresponds to one staining dot per area. A CFS grade of 0 represents complete corneal clearing.
Time Frame
36 months (Periods 1 + 2)
Title
Efficacy Secondary Outcome Measures in Entire study: Conjunctival fluorescein staining score at each visit in Entire study
Description
Staining using fluorescein (provided by the Sponsor) will be graded using the modified Oxford scale (7-point ordinal scale, score 0, 0.5, and 1 to 5 per area [cornea + nasal and temporal conjunctiva]) for cornea and conjunctiva separately. On this modified scale, the score 0 corresponds to no staining dots and the score 0.5 corresponds to one staining dot per area. A CFS grade of 0 represents complete corneal clearing.
Time Frame
36 months (Periods 1 + 2)
Title
Efficacy Secondary Outcome Measures in Entire study: Change from Baseline in Conjunctival fluorescein staining score at each visit in Entire study
Description
Staining using fluorescein (provided by the Sponsor) will be graded using the modified Oxford scale (7-point ordinal scale, score 0, 0.5, and 1 to 5 per area [cornea + nasal and temporal conjunctiva]) for cornea and conjunctiva separately. On this modified scale, the score 0 corresponds to no staining dots and the score 0.5 corresponds to one staining dot per area. A CFS grade of 0 represents complete corneal clearing.
Time Frame
36 months (Periods 1 + 2)
Title
Efficacy Secondary Outcome Measures in Entire study: SANDE symptoms score at each visit in Entire study
Description
SANDE is Symptom Assessment iN Dry Eye. The self-administered Symptom Assessment iN Dry Eye (SANDE) questionnaire must be completed by the patient him/herself. SANDE questionnaire will be used to score both severity and frequency of dry eye symptoms. This 2-item frequency- and severity-based visual analogue scales (0-100mm ranging respectively from" rarely" to "all the time", and from "very mild" to "very severe") is short and quick, and provides reliable measure for Dry Eye Disease symptoms assessment. Symptoms will be evaluated for both eyes together. A negative change from baseline (Period 1) or from Month 12 (Period 2) will indicate an improvement in dry eye disease symptoms.
Time Frame
36 months (Periods 1 + 2)
Title
Efficacy Secondary Outcome Measures in Entire study: Change from Baseline in SANDE symptoms score at each visit in Entire study
Description
SANDE is Symptom Assessment iN Dry Eye. The self-administered Symptom Assessment iN Dry Eye (SANDE) questionnaire must be completed by the patient him/herself. SANDE questionnaire will be used to score both severity and frequency of dry eye symptoms. This 2-item frequency- and severity-based visual analogue scales (0-100mm ranging respectively from" rarely" to "all the time", and from "very mild" to "very severe") is short and quick, and provides reliable measure for Dry Eye Disease symptoms assessment. Symptoms will be evaluated for both eyes together. A negative change from baseline (Period 1) or from Month 12 (Period 2) will indicate an improvement in dry eye disease symptoms.
Time Frame
36 months (Periods 1 + 2)
Title
Efficacy Secondary Outcome Measures in Entire study: Symptoms score (5-point scale) at each visit, for each of the five symptoms assessed in Entire study
Description
The 5-point Likert scales are a self-administered questionnaire and must be completed by the patient him/herself. Burning/stinging, foreign body sensation, eye dryness, photophobia, pain and blurred/poor vision, will be assessed by the study patients using a 5-point Likert scale from none to very severe (0 to 4). Symptoms will be evaluated for both eyes together.
Time Frame
36 months (Periods 1 + 2)
Title
Efficacy Secondary Outcome Measures in Entire study: Change from Baseline in Symptoms score (5-point scale) at each visit, for each of the five symptoms assessed in Entire study
Description
The 5-point Likert scales are a self-administered questionnaire and must be completed by the patient him/herself. Burning/stinging, foreign body sensation, eye dryness, photophobia, pain and blurred/poor vision, will be assessed by the study patients using a 5-point Likert scale from none to very severe (0 to 4). Symptoms will be evaluated for both eyes together.
Time Frame
36 months (Periods 1 + 2)
Title
Efficacy Secondary Outcome Measures in Entire study: TBUT at each visit in Entire study
Description
TBUT is Tear Breakup Time. Tear break-up time (TBUT) will be measured by determining the time to tear break-up. The examiner will monitor the integrity of the tear film, noting the time it takes to form lacunae (clear spaces in the tear film) from the time that the eye is opened after the last blink. A higher value means longer time to tear break-up which is better. A positive change from baseline (Period 1) or from Month 12 (Period 2) will indicate improvement.
Time Frame
36 months (Periods 1 + 2)
Title
Efficacy Secondary Outcome Measures in Entire study: Change from Baseline in TBUT at each visit in Entire study
Description
TBUT is Tear Breakup Time. Tear break-up time (TBUT) will be measured by determining the time to tear break-up. The examiner will monitor the integrity of the tear film, noting the time it takes to form lacunae (clear spaces in the tear film) from the time that the eye is opened after the last blink. A higher value means longer time to tear break-up which is better. A positive change from baseline (Period 1) or from Month 12 (Period 2) will indicate improvement.
Time Frame
36 months (Periods 1 + 2)
Title
Efficacy Secondary Outcome Measures in Entire study: Schirmer test at Month 12, Month 24 and Month 36 visits
Description
The rounded bent end of a sterile strip will be inserted into the lower conjunctival sac over the temporal one-third of the lower eyelid margin. After 5 minutes have elapsed the Schirmer test strip will be removed and the length of the tear absorption on the strip will be measured. A higher value means higher tear absorption which is better. A positive change from baseline (Period 1) or from Month 12 (Period 2) will indicate improvement.
Time Frame
Month 12, Month 24 and Month 36 visits
Title
Efficacy Secondary Outcome Measures in Entire study: Change from Baseline in Schirmer test at Month 12, Month 24 and Month 36 visits
Description
The rounded bent end of a sterile strip will be inserted into the lower conjunctival sac over the temporal one-third of the lower eyelid margin. After 5 minutes have elapsed the Schirmer test strip will be removed and the length of the tear absorption on the strip will be measured. A higher value means higher tear absorption which is better. A positive change from baseline (Period 1) or from Month 12 (Period 2) will indicate improvement.
Time Frame
Month 12, Month 24 and Month 36 visits
Title
Efficacy Secondary Outcome Measures in Entire study: Use of Artificial Tears over the last week at each visit in Entire study
Description
The use of artificial tears will be monitored over the course of the study for each patient. Patients will be asked about the average number of times per day artificial tears was used over the last week, and number of days they were not used during the week preceding the visits.
Time Frame
36 months (Periods 1 + 2)
Title
Efficacy Secondary Outcome Measures in Entire study: Change from Baseline in Use of Artificial Tears over the last week at each visit in Entire study
Description
The use of artificial tears will be monitored over the course of the study for each patient. Patients will be asked about the average number of times per day artificial tears was used over the last week, and number of days they were not used during the week preceding the visits.
Time Frame
36 months (Periods 1 + 2)
Title
Quality of Life Outcome: DEQS overall score at Month 6, Month 12, Month 18, Month 24, Month 30 and Month 36 Visits.
Description
DEQS is Dry Eye related Quality of life Score. The DEQS consists of 15 items related to dry eye symptoms and influence on daily life, and the overall degree of Quality of Life impairment is calculated as a summary score (0 to 100), lower score meaning better.
Time Frame
Month 6, Month 12, Month 18, Month 24, Month 30 and Month 36 Visits.
Title
Quality of Life Outcome: Change from Baseline in DEQS at Month 6, Month 12, Month 18, Month 24, Month 30 and Month 36 Visits. Change from Month 12 will also be summarized for scores collected in Period 2.
Description
DEQS is Dry Eye related Quality of life Score. The DEQS consists of 15 items related to dry eye symptoms and influence on daily life, and the overall degree of Quality of Life impairment is calculated as a summary score (0 to 100), lower score meaning better.
Time Frame
Month 6, Month 12, Month 18, Month 24, Month 30 and Month 36 Visits
Title
Safety and Tolerability Outcome: IOP at Month 12, Month 24 and Month 36 visits
Description
IOP is Intraocular pressure
Time Frame
Month 12, Month 24 and Month 36 visits
Title
Safety and Tolerability Outcome: Change from Baseline in IOP at Month 12, Month 24 and Month 36 visits
Description
IOP is Intraocular pressure
Time Frame
Month 12, Month 24 and Month 36 visits
Title
Safety and Tolerability Outcome: BCDVA at Month 6, Month 12, Month 24 and Month 36 visits
Description
BCDVA is Best Corrected Distance Visual Acuity. Lowest visual acuity corresponds to Snellen value 20/200, while best visual acuity corresponds to Snellen value 20/20 or higher.
Time Frame
Month 6, Month 12, Month 24 and Month 36 visits
Title
Safety and Tolerability Outcome: Change from Baseline in BCDVA at Month 6, Month 12, Month 24 and Month 36 visits
Description
BCDVA is Best Corrected Distance Visual Acuity. Lowest visual acuity corresponds to Snellen value 20/200, while best visual acuity corresponds to Snellen value 20/20 or higher.
Time Frame
Month 6, Month 12, Month 24 and Month 36 visits
Title
Safety and Tolerability Outcome: Incidence of ocular and systemic AEs over the three-year study period.
Description
AE is Adverse Event
Time Frame
36 months (Periods 1 + 2)
Title
Safety and Tolerability Outcome: Severity of ocular and systemic AEs over the three-year study period.
Description
AE is Adverse Event
Time Frame
36 months (Periods 1 + 2)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: In the opinion of the investigator, the patient is capable of understanding and complying with protocol requirements. The patient has signed and dated a written informed consent form and any required privacy authorization prior to the initiation of any study procedures. Male or female patient is aged 18 years or above. At least 4 weeks of use of tear substitutes prior to the Baseline Visit DED patients with severe keratitis defined as the following: CFS score of 3, 4 or 5 on the modified Oxford scale in at least one eye at Baseline Visits, AND Schirmer test without anaesthesia scored <10 mm/5min in the same eye at Baseline Visit, AND At least two moderate to very severe symptoms of dry eye disease with a score ≥2 (severity graded on a 0 to 4 grade scale), among the following symptoms: burning/stinging, foreign body sensation, eye dryness, eye pain and blurred/poor vision at Baseline Visit. Patient must be willing and able to undergo and return for scheduled study-related examinations. Exclusion Criteria: Active herpes keratitis or history of ocular herpes. History of ocular trauma or ocular infection (viral, bacterial, fungal, protozoal) within 90 days before the Baseline Visit. Any ocular diseases other than DED requiring topical ocular treatment during the course of the study. Patients taking preservative-free IOP lowering medications are eligible for study enrolment. Concurrent ocular allergy (including seasonal conjunctivitis) or chronic conjunctivitis other than dry eye. Anticipated use of temporary punctal plugs during the study. Patients with punctal plugs placed prior to the Baseline Visit are eligible for enrolment; however, punctal plugs must remain in place during the study. Best corrected distance visual acuity (BCDVA) score ≤ 20/200 Snellen in each eye. Presence or history of any systemic or ocular disorder, condition or disease that could possibly interfere with the conduct of the required study procedures or the interpretation of study results or judged by the investigator to be incompatible with the study (e.g., diabetes with glycemia out of range, thyroid malfunction, uncontrolled autoimmune disease, current systemic infections, ocular infection…). Known hypersensitivity to one of the components of the study or procedural medications (e.g., fluorescein, etc.). History of ophthalmic malignancy History of malignancy (other than ophthalmic) in the last 5 years. Anticipated change during course of the study in the dose of systemic medications that could affect a dry eye condition [mainly, estrogen-progesterone or other estrogen derivatives (only allowed for post-menopausal women), pilocarpine, isotretinoine, tetracycline, antihistamines, tricyclic antidepressants, anxiolytics, antimuscarinics, beta-blocking agents, phenothiazines, omega-3, systemic corticosteroids]. These treatments are allowed during the study provided they remain stable throughout the course of the study. Use of topical ciclosporin in the past 3 months prior to Baseline visit. Any change in systemic immunosuppressant drugs within 30 days before the Baseline Visit or anticipated change during the course of the study. Pregnancy or lactation at the Baseline Visit. Women of childbearing potential not using a medically acceptable, highly effective method of birth control (such as hormonal implants, injectable or oral contraceptives together with condoms, some intrauterine devices, sexual abstinence or vasectomised partner) from the Baseline Visit throughout the conduct of the study treatment periods and up to 2 weeks after the study end. Post-menopausal women (two years without menstruation) do not need to use any method of birth control. Participation in a clinical trial with an investigational substance within the past 30 days prior to Baseline Visit. Participation in another clinical study at the same time as the present study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jean-Sébastien GARRIGUE, PhD
Organizational Affiliation
Santen SAS
Official's Role
Study Chair
Facility Information:
Facility Name
Fakultní Nemocnice Brno
City
Brno
State/Province
Jihomoravský
ZIP/Postal Code
62500
Country
Czechia
Facility Name
Fakultni Nemocnice Ostrava, Oční Klinika
City
Ostrava
State/Province
Moravskoslezský
ZIP/Postal Code
70800
Country
Czechia
Facility Name
University Hospital Hradec Kralove
City
Hradec Králové
State/Province
Nový Hradec Králové
ZIP/Postal Code
50005
Country
Czechia
Facility Name
Ocni klinika OFTEX
City
Pardubice
State/Province
Pardubický
ZIP/Postal Code
53002
Country
Czechia
Facility Name
MEDOKO s.r.o.
City
Prague
State/Province
Praha
ZIP/Postal Code
10800
Country
Czechia
Facility Name
Axon clinical s.r.o.
City
Prague
State/Province
Praha
ZIP/Postal Code
15000
Country
Czechia
Facility Name
Masarykova nemocnice, Ocni oddeleni
City
Ústí Nad Labem
State/Province
Ustecky
ZIP/Postal Code
4001
Country
Czechia
Facility Name
Nemocnice Teplice, Ocni Oddeleni
City
Teplice
State/Province
Ústecký
ZIP/Postal Code
41505
Country
Czechia
Facility Name
Hospices Civils de Lyon - Hopital de la Croix-Rousse
City
Lyon
State/Province
Rhône-Alpes
ZIP/Postal Code
69317
Country
France
Facility Name
Hopitaux Universitaires Paris-Sud - Hopital Bicetre
City
Le Kremlin-Bicêtre
State/Province
Île-de-France
ZIP/Postal Code
94270
Country
France
Facility Name
Hôpital des Quinze-Vingts
City
Paris
State/Province
Île-de-France
ZIP/Postal Code
75012
Country
France
Facility Name
Hopitaux Universitaires Paris Nord Val de Seine - Hopital Bichat - Claude Bernard
City
Paris
State/Province
Île-de-France
ZIP/Postal Code
75877
Country
France
Facility Name
Universita degli Studi di Milano - Clinica Oculistica I
City
Milan
State/Province
Lombardia
ZIP/Postal Code
20122
Country
Italy
Facility Name
Universita degli Studi di Milano - Ospedale San Giuseppe - Clinica Oculistica (University Eye Clinic)
City
Milan
State/Province
Lombardia
ZIP/Postal Code
20123
Country
Italy
Facility Name
ASST Santi Paolo e Carlo - Ospedale San Paolo Polo Universitario - Clinica Oculistica III
City
Milan
State/Province
Lombardia
ZIP/Postal Code
20142
Country
Italy
Facility Name
Polo Universita degli Studi di Milano - Ospedale Luigi Sacco - Clinica Oculistica (Eye Clinic)
City
Milan
State/Province
Lombardia
ZIP/Postal Code
20157
Country
Italy
Facility Name
Universita degli Studi di Pavia - Fondazione IRCCS Policlinico San Matteo - Clinica Oculistic
City
Pavia
State/Province
Lombardia
ZIP/Postal Code
27100
Country
Italy
Facility Name
Azienda Ospedaliera Universitaria Policlinico Gaetano Martino - Messina
City
Messina
State/Province
Sicilia
ZIP/Postal Code
98128
Country
Italy
Facility Name
Universita degli Studi di Padova - Azienda Ospedaliera di Padova - Clinica Oculistica
City
Padova
State/Province
Veneto
ZIP/Postal Code
35128
Country
Italy
Facility Name
Samodzielny Publiczny Szpital Kliniczny Nr 1 Klinika Diagnostyki i Mikrochirurgii Jaskry Oddział Okulistyki
City
Lublin
State/Province
Lubelskie
ZIP/Postal Code
20079
Country
Poland
Facility Name
Niepubliczny Zaklad Opieki Zdrowotnej Oko-Laser
City
Kraków
State/Province
Malopolskie
ZIP/Postal Code
30644
Country
Poland
Facility Name
Gabinet Okulistyczny Prof. Edward Wylęgała
City
Katowice
State/Province
Silesia
ZIP/Postal Code
40594
Country
Poland
Facility Name
Uniwersyteckie Centrum Kliniczne Śląskiego Uniwersytetu Medycznego w Katowicach
City
Katowice
State/Province
Silesia
ZIP/Postal Code
40952
Country
Poland
Facility Name
Retina Szpital Okulistyczny
City
Warszawa
State/Province
Warszawskie
ZIP/Postal Code
1364
Country
Poland
Facility Name
Uniwersytecki Szpital Kiliniczny IM. Jana Milkulicza-Radeckiego we Wroclawiu
City
Wrocław
State/Province
Wrocławiu
ZIP/Postal Code
50556
Country
Poland
Facility Name
Federal State Institution Intersectoral Research and Technology Complex Eye microsurgery n.a. academician S.N. Fyodorov - Cheboksary
City
Cheboksary
State/Province
Chuvashia
ZIP/Postal Code
428028
Country
Russian Federation
Facility Name
Ivanovo Regional Clinical Hospital
City
Ivanov
State/Province
Ivanovo
ZIP/Postal Code
153040
Country
Russian Federation
Facility Name
NMRC ISTC Eye Microsurgery n. a. Fyodorov - Moscow
City
Moscow
State/Province
Moskva
ZIP/Postal Code
126486
Country
Russian Federation
Facility Name
State Budget Educational Institution of High Professional Education Moscow State Medical Stomatology University named after A.I.Evdokimov of MoH of RF
City
Moskow
State/Province
Moskva
ZIP/Postal Code
111398
Country
Russian Federation
Facility Name
Saint Petersburg State Pediatric Medical University
City
Saint Petersburg
State/Province
Sankt-Peterburg
ZIP/Postal Code
194100
Country
Russian Federation
Facility Name
First Saint Petersburg State Medical University named after academician I.P. Pavlov
City
Saint Petersburg
State/Province
Sankt-Peterburg
ZIP/Postal Code
197002
Country
Russian Federation
Facility Name
FSBI The Academician S.N. Fyodorov IRTC Eye Microsurgery of the Minzdrava - Novosibirsk
City
Novosibirsk
ZIP/Postal Code
630120
Country
Russian Federation
Facility Name
GBOU VPO Omsk State Medical Academy, Ophthalmology Department
City
Omsk
ZIP/Postal Code
644024
Country
Russian Federation
Facility Name
Saratov Railway Clinic
City
Saratov
ZIP/Postal Code
41004
Country
Russian Federation
Facility Name
Cartujavision Oftalmologia
City
Sevilla
State/Province
Andalucia
ZIP/Postal Code
41092
Country
Spain
Facility Name
Hospital Clinico Universitario Lozano Blesa de Zaragoza
City
Zaragosa
State/Province
Aragon
ZIP/Postal Code
50009
Country
Spain
Facility Name
Institut Catala de Retina
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
8017
Country
Spain
Facility Name
Centro de Oftalmología Barraquer
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
8021
Country
Spain
Facility Name
Hospital Clinic de Barcelona (Hospital Clinic i Provincial)
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
8036
Country
Spain
Facility Name
Hospital Universitario Donostia, Oftalmalogia
City
San Sebastián
State/Province
Euskal Autonomia Erkidegoa
ZIP/Postal Code
20014
Country
Spain
Facility Name
Fundación Oftalmológica del Mediterráneo
City
Valencia
ZIP/Postal Code
46015
Country
Spain
Facility Name
Bayındır Kavaklidere Hospital Ophthalmology department
City
Ankara
State/Province
Anatolia
ZIP/Postal Code
6680
Country
Turkey
Facility Name
Ankara Üniversitesi Tıp Fakültesi Göz Hastalıkları Anabilim Dalı Vehbi Koç Göz Hastanesi
City
Mamak
State/Province
Ankara
ZIP/Postal Code
6620
Country
Turkey
Facility Name
Ege Universitesi Tip Fakultesi Hastanesi Goz Hastaliklari Anabilim Dali
City
Bornova
State/Province
Izmir
ZIP/Postal Code
35100
Country
Turkey
Facility Name
Selcuk University School of Medicine Ophthalmology department
City
Konya
State/Province
Selcuklu
ZIP/Postal Code
42130
Country
Turkey

12. IPD Sharing Statement

Learn more about this trial

3-year Study in Dry Eye Disease Patients With Severe Keratitis Receiving Ikervis® (1mg/mL Ciclosporin)

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