Clinical trial NCT04144413: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Dry Eye Disease With Severe Keratitis
Lead sponsor: Santen SAS
Sponsor class: INDUSTRY
First posted: 2019-10-30
Enrollment: 350
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: Months 3, 6, 9, and 12
Secondary outcomes:
measure: Corneal Fluorescein Staining (CFS) Score and Change From Baseline by Visit
timeFrame: Baseline, Months 3, 6, 9 and 12
Other outcomes:
Locations:
city: Brno
country: Czechia
facility: Fakultní Nemocnice Brno
state: Jihomoravský
city: Ostrava
country: Czechia
facility: Fakultni Nemocnice Ostrava, Oční Klinika
state: Moravskoslezský
city: Hradec Králové
country: Czechia
facility: University Hospital Hradec Kralove
state: Nový Hradec Králové
city: Pardubice
country: Czechia
facility: Ocni klinika OFTEX
state: Pardubický
city: Prague
country: Czechia
facility: MEDOKO s.r.o.
state: Praha
city: Prague
country: Czechia
facility: Axon clinical s.r.o.
state: Praha
city: Ústí Nad Labem
country: Czechia
facility: Masarykova nemocnice, Ocni oddeleni
state: Ustecky
city: Teplice
country: Czechia
facility: Nemocnice Teplice, Ocni Oddeleni
state: Ústecký
city: Lyon
country: France
facility: Hospices Civils de Lyon - Hopital de la Croix-Rousse
state: Rhône-Alpes
city: Le Kremlin-Bicêtre
country: France
facility: Hopitaux Universitaires Paris-Sud - Hopital Bicetre
state: Île-de-France
city: Paris
country: France
facility: Hôpital des Quinze-Vingts
state: Île-de-France
city: Paris
country: France
facility: Hopitaux Universitaires Paris Nord Val de Seine - Hopital Bichat - Claude Bernard
state: Île-de-France
city: Milan
country: Italy
facility: Universita degli Studi di Milano - Clinica Oculistica I
state: Lombardia
city: Milan
country: Italy
facility: Universita degli Studi di Milano - Ospedale San Giuseppe - Clinica Oculistica (University Eye Clinic)
state: Lombardia
city: Milan
country: Italy
facility: ASST Santi Paolo e Carlo - Ospedale San Paolo Polo Universitario - Clinica Oculistica III
state: Lombardia
city: Milan
country: Italy
facility: Polo Universita degli Studi di Milano - Ospedale Luigi Sacco - Clinica Oculistica (Eye Clinic)
state: Lombardia
city: Pavia
country: Italy
facility: Universita degli Studi di Pavia - Fondazione IRCCS Policlinico San Matteo - Clinica Oculistic
state: Lombardia
city: Messina
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Gaetano Martino - Messina
state: Sicilia
city: Padova
country: Italy
facility: Universita degli Studi di Padova - Azienda Ospedaliera di Padova - Clinica Oculistica
state: Veneto
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny Nr 1 Klinika Diagnostyki i Mikrochirurgii Jaskry Oddział Okulistyki
state: Lubelskie
city: Kraków
country: Poland
facility: Niepubliczny Zaklad Opieki Zdrowotnej Oko-Laser
state: Malopolskie
city: Katowice
country: Poland
facility: Gabinet Okulistyczny Prof. Edward Wylęgała
state: Silesia
city: Katowice
country: Poland
facility: Uniwersyteckie Centrum Kliniczne Śląskiego Uniwersytetu Medycznego w Katowicach
state: Silesia
city: Warszawa
country: Poland
facility: Retina Szpital Okulistyczny
state: Warszawskie
city: Wrocław
country: Poland
facility: Uniwersytecki Szpital Kiliniczny IM. Jana Milkulicza-Radeckiego we Wroclawiu
state: Wrocławiu
city: Cheboksary
country: Russian Federation
facility: Federal State Institution Intersectoral Research and Technology Complex Eye microsurgery n.a. academician S.N. Fyodorov - Cheboksary
state: Chuvashia
city: Ivanov
country: Russian Federation
facility: Ivanovo Regional Clinical Hospital
state: Ivanovo
city: Moscow
country: Russian Federation
facility: NMRC ISTC Eye Microsurgery n. a. Fyodorov - Moscow
state: Moskva
city: Moskow
country: Russian Federation
facility: State Budget Educational Institution of High Professional Education Moscow State Medical Stomatology University named after A.I.Evdokimov of MoH of RF
state: Moskva
city: Saint Petersburg
country: Russian Federation
facility: Saint Petersburg State Pediatric Medical University
state: Sankt-Peterburg
city: Saint Petersburg
country: Russian Federation
facility: First Saint Petersburg State Medical University named after academician I.P. Pavlov
state: Sankt-Peterburg
city: Novosibirsk
country: Russian Federation
facility: FSBI The Academician S.N. Fyodorov IRTC Eye Microsurgery of the Minzdrava - Novosibirsk
city: Omsk
country: Russian Federation
facility: GBOU VPO Omsk State Medical Academy, Ophthalmology Department
city: Saratov
country: Russian Federation
facility: Saratov Railway Clinic
city: Sevilla
country: Spain
facility: Cartujavision Oftalmologia
state: Andalucia
city: Zaragosa
country: Spain
facility: Hospital Clinico Universitario Lozano Blesa de Zaragoza
state: Aragon
city: Barcelona
country: Spain
facility: Institut Catala de Retina
state: Catalunya
city: Barcelona
country: Spain
facility: Centro de Oftalmología Barraquer
state: Catalunya
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona (Hospital Clinic i Provincial)
state: Catalunya
city: San Sebastián
country: Spain
facility: Hospital Universitario Donostia, Oftalmalogia
state: Euskal Autonomia Erkidegoa
city: Valencia
country: Spain
facility: Fundación Oftalmológica del Mediterráneo
city: Ankara
country: Turkey
facility: Bayındır Kavaklidere Hospital Ophthalmology department
state: Anatolia
city: Mamak
country: Turkey
facility: Ankara Üniversitesi Tıp Fakültesi Göz Hastalıkları Anabilim Dalı Vehbi Koç Göz Hastanesi
state: Ankara
city: Bornova
country: Turkey
facility: Ege Universitesi Tip Fakultesi Hastanesi Goz Hastaliklari Anabilim Dali
state: Izmir
city: Konya
country: Turkey
facility: Selcuk University School of Medicine Ophthalmology department
state: Selcuklu
Study officials:
affiliation: Santen SAS
name: Jean-Sébastien GARRIGUE, PhD
role: STUDY_CHAIR
References: