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

Phase 3
Completed
Conditions
Dry Eye Disease With Severe Keratitis
Interventions
Registration Number
NCT04144413
Lead Sponsor
Santen SAS
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

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
350
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Period 2 Masked IkervisMasked IkervisPeriod 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.
Period 1 Open-label IkervisOpen-label IkervisPeriod 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.
Primary Outcome Measures
NameTimeMethod
The Correlation Between Mean Change From Baseline in Corneal Fluorescein Staining (CFS) Score and Symptom Assessment iN Dry Eye (SANDE) Symptoms Score at Each Visit.Months 3, 6, 9, and 12

For analysis, SCC (Spearman Correlation Coefficient) and its 95% Confidence Interval were calculated for the correlation analysis between change from baseline in CFS (Corneal Fluorescein Staining) score at visit X and SANDE (Symptom Assessment iN Dry Eye) symptoms score using the FAS (Full Analysis Set) Period 1 Population.

Secondary Outcome Measures
NameTimeMethod
Corneal Fluorescein Staining (CFS) Score and Change From Baseline by VisitBaseline, Months 3, 6, 9 and 12

Period 1 is Baseline to Month 12 included. CFS is Corneal Fluorescein Score. Staining using fluorescein was 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.

Trial Locations

Locations (45)

Hopitaux Universitaires Paris-Sud - Hopital Bicetre

🇫🇷

Le Kremlin-Bicêtre, Île-de-France, France

Hôpital des Quinze-Vingts

🇫🇷

Paris, Île-de-France, France

Hopitaux Universitaires Paris Nord Val de Seine - Hopital Bichat - Claude Bernard

🇫🇷

Paris, Île-de-France, France

Gabinet Okulistyczny Prof. Edward Wylęgała

🇵🇱

Katowice, Silesia, Poland

Uniwersyteckie Centrum Kliniczne Śląskiego Uniwersytetu Medycznego w Katowicach

🇵🇱

Katowice, Silesia, Poland

Fakultní Nemocnice Brno

🇨🇿

Brno, Jihomoravský, Czechia

Fakultni Nemocnice Ostrava, Oční Klinika

🇨🇿

Ostrava, Moravskoslezský, Czechia

Ocni klinika OFTEX

🇨🇿

Pardubice, Pardubický, Czechia

Axon clinical s.r.o.

🇨🇿

Prague, Praha, Czechia

MEDOKO s.r.o.

🇨🇿

Prague, Praha, Czechia

Masarykova nemocnice, Ocni oddeleni

🇨🇿

Ústí Nad Labem, Ustecky, Czechia

Nemocnice Teplice, Ocni Oddeleni

🇨🇿

Teplice, Ústecký, Czechia

Hospices Civils de Lyon - Hopital de la Croix-Rousse

🇫🇷

Lyon, Rhône-Alpes, France

Universita degli Studi di Milano - Clinica Oculistica I

🇮🇹

Milan, Lombardia, Italy

Universita degli Studi di Milano - Ospedale San Giuseppe - Clinica Oculistica (University Eye Clinic)

🇮🇹

Milan, Lombardia, Italy

ASST Santi Paolo e Carlo - Ospedale San Paolo Polo Universitario - Clinica Oculistica III

🇮🇹

Milan, Lombardia, Italy

Polo Universita degli Studi di Milano - Ospedale Luigi Sacco - Clinica Oculistica (Eye Clinic)

🇮🇹

Milan, Lombardia, Italy

Universita degli Studi di Pavia - Fondazione IRCCS Policlinico San Matteo - Clinica Oculistic

🇮🇹

Pavia, Lombardia, Italy

Azienda Ospedaliera Universitaria Policlinico Gaetano Martino - Messina

🇮🇹

Messina, Sicilia, Italy

Universita degli Studi di Padova - Azienda Ospedaliera di Padova - Clinica Oculistica

🇮🇹

Padova, Veneto, Italy

Samodzielny Publiczny Szpital Kliniczny Nr 1 Klinika Diagnostyki i Mikrochirurgii Jaskry Oddział Okulistyki

🇵🇱

Lublin, Lubelskie, Poland

Niepubliczny Zaklad Opieki Zdrowotnej Oko-Laser

🇵🇱

Kraków, Malopolskie, Poland

Retina Szpital Okulistyczny

🇵🇱

Warszawa, Warszawskie, Poland

Federal State Institution Intersectoral Research and Technology Complex Eye microsurgery n.a. academician S.N. Fyodorov - Cheboksary

🇷🇺

Cheboksary, Chuvashia, Russian Federation

Uniwersytecki Szpital Kiliniczny IM. Jana Milkulicza-Radeckiego we Wroclawiu

🇵🇱

Wrocław, Wrocławiu, Poland

Ivanovo Regional Clinical Hospital

🇷🇺

Ivanov, Ivanovo, Russian Federation

NMRC ISTC Eye Microsurgery n. a. Fyodorov - Moscow

🇷🇺

Moscow, Moskva, Russian Federation

Saint Petersburg State Pediatric Medical University

🇷🇺

Saint Petersburg, Sankt-Peterburg, Russian Federation

State Budget Educational Institution of High Professional Education Moscow State Medical Stomatology University named after A.I.Evdokimov of MoH of RF

🇷🇺

Moskow, Moskva, Russian Federation

First Saint Petersburg State Medical University named after academician I.P. Pavlov

🇷🇺

Saint Petersburg, Sankt-Peterburg, Russian Federation

GBOU VPO Omsk State Medical Academy, Ophthalmology Department

🇷🇺

Omsk, Russian Federation

FSBI The Academician S.N. Fyodorov IRTC Eye Microsurgery of the Minzdrava - Novosibirsk

🇷🇺

Novosibirsk, Russian Federation

Saratov Railway Clinic

🇷🇺

Saratov, Russian Federation

Hospital Clinico Universitario Lozano Blesa de Zaragoza

🇪🇸

Zaragosa, Aragon, Spain

Cartujavision Oftalmologia

🇪🇸

Sevilla, Andalucia, Spain

Institut Catala de Retina

🇪🇸

Barcelona, Catalunya, Spain

Centro de Oftalmología Barraquer

🇪🇸

Barcelona, Catalunya, Spain

Hospital Universitario Donostia, Oftalmalogia

🇪🇸

San Sebastián, Euskal Autonomia Erkidegoa, Spain

Hospital Clinic de Barcelona (Hospital Clinic i Provincial)

🇪🇸

Barcelona, Catalunya, Spain

Bayındır Kavaklidere Hospital Ophthalmology department

🇹🇷

Ankara, Anatolia, Turkey

Fundación Oftalmológica del Mediterráneo

🇪🇸

Valencia, Spain

Ankara Üniversitesi Tıp Fakültesi Göz Hastalıkları Anabilim Dalı Vehbi Koç Göz Hastanesi

🇹🇷

Mamak, Ankara, Turkey

Ege Universitesi Tip Fakultesi Hastanesi Goz Hastaliklari Anabilim Dali

🇹🇷

Bornova, Izmir, Turkey

Selcuk University School of Medicine Ophthalmology department

🇹🇷

Konya, Selcuklu, Turkey

University Hospital Hradec Kralove

🇨🇿

Hradec Králové, Nový Hradec Králové, Czechia

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