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

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)

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

Study Overview

• Status: Completed
• Conditions: Dry Eye Disease With Severe Keratitis
• Intervention / Treatment: Drug: Open-label Ikervis; Drug: Masked Ikervis; Other: Vehicle Comparator: Masked Vehicle

• Study Type: Interventional
• Enrollment (Actual): 350
• Phase: Phase 3

Contacts and Locations

Study Locations

• Czechia
  • Jihomoravský
    • Brno, Jihomoravský, Czechia, 62500
      • Fakultni nemocnice Brno
  • Moravskoslezský
    • Ostrava, Moravskoslezský, Czechia, 70800
      • Fakultni Nemocnice Ostrava, Oční Klinika
  • Nový Hradec Králové
    • Hradec Králové, Nový Hradec Králové, Czechia, 50005
      • University hospital Hradec Králové
  • Pardubický
    • Pardubice, Pardubický, Czechia, 53002
      • Ocni klinika Oftex
  • Praha
    • Prague, Praha, Czechia, 10800
      • MEDOKO s.r.o.
    • Prague, Praha, Czechia, 15000
      • Axon Clinical s.r.o.
  • Ustecky
    • Ústí Nad Labem, Ustecky, Czechia, 4001
      • Masarykova nemocnice, Ocni oddeleni
  • Ústecký
    • Teplice, Ústecký, Czechia, 41505
      • Nemocnice Teplice, Ocni Oddeleni
• France
  • Rhône-Alpes
    • Lyon, Rhône-Alpes, France, 69317
      • Hospices Civils de Lyon - Hôpital de la Croix-Rousse
  • Île-de-France
    • Le Kremlin-Bicêtre, Île-de-France, France, 94270
      • Hopitaux Universitaires Paris-Sud - Hopital Bicetre
    • Paris, Île-de-France, France, 75012
      • Hôpital des Quinze-Vingts
    • Paris, Île-de-France, France, 75877
      • Hopitaux Universitaires Paris Nord Val de Seine - Hopital Bichat - Claude Bernard
• Italy
  • Lombardia
    • Milan, Lombardia, Italy, 20122
      • Universita degli Studi di Milano - Clinica Oculistica I
    • Milan, Lombardia, Italy, 20123
      • Universita degli Studi di Milano - Ospedale San Giuseppe - Clinica Oculistica (University Eye Clinic)
    • Milan, Lombardia, Italy, 20142
      • ASST Santi Paolo e Carlo - Ospedale San Paolo Polo Universitario - Clinica Oculistica III
    • Milan, Lombardia, Italy, 20157
      • Polo Universita degli Studi di Milano - Ospedale Luigi Sacco - Clinica Oculistica (Eye Clinic)
    • Pavia, Lombardia, Italy, 27100
      • Universita degli Studi di Pavia - Fondazione IRCCS Policlinico San Matteo - Clinica Oculistic
  • Sicilia
    • Messina, Sicilia, Italy, 98128
      • Azienda Ospedaliera Universitaria Policlinico Gaetano Martino - Messina
  • Veneto
    • Padova, Veneto, Italy, 35128
      • Universita degli Studi di Padova - Azienda Ospedaliera di Padova - Clinica Oculistica
• Poland
  • Lubelskie
    • Lublin, Lubelskie, Poland, 20079
      • Samodzielny Publiczny Szpital Kliniczny Nr 1 Klinika Diagnostyki i Mikrochirurgii Jaskry Oddział Okulistyki
  • Malopolskie
    • Kraków, Malopolskie, Poland, 30644
      • Niepubliczny Zaklad Opieki Zdrowotnej Oko-Laser
  • Silesia
    • Katowice, Silesia, Poland, 40594
      • Gabinet Okulistyczny Prof. Edward Wylęgała
    • Katowice, Silesia, Poland, 40952
      • Uniwersyteckie Centrum Kliniczne Śląskiego Uniwersytetu Medycznego w Katowicach
  • Warszawskie
    • Warszawa, Warszawskie, Poland, 1364
      • Retina Szpital Okulistyczny
  • Wrocławiu
    • Wrocław, Wrocławiu, Poland, 50556
      • Uniwersytecki Szpital Kiliniczny IM. Jana Milkulicza-Radeckiego we Wroclawiu
• Russian Federation
  • Novosibirsk, Russian Federation, 630120
    • FSBI The Academician S.N. Fyodorov IRTC Eye Microsurgery of the Minzdrava - Novosibirsk
  • Omsk, Russian Federation, 644024
    • GBOU VPO Omsk State Medical Academy, Ophthalmology Department
  • Saratov, Russian Federation, 41004
    • Saratov Railway Clinic
  • Chuvashia
    • Cheboksary, Chuvashia, Russian Federation, 428028
      • Federal State Institution Intersectoral Research and Technology Complex Eye microsurgery n.a. academician S.N. Fyodorov - Cheboksary
  • Ivanovo
    • Ivanov, Ivanovo, Russian Federation, 153040
      • Ivanovo Regional Clinical Hospital
  • Moskva
    • Moscow, Moskva, Russian Federation, 126486
      • NMRC ISTC Eye Microsurgery n. a. Fyodorov - Moscow
    • Moskow, Moskva, Russian Federation, 111398
      • State Budget Educational Institution of High Professional Education Moscow State Medical Stomatology University named after A.I.Evdokimov of MoH of RF
  • Sankt-Peterburg
    • Saint Petersburg, Sankt-Peterburg, Russian Federation, 194100
      • Saint Petersburg State Pediatric Medical University
    • Saint Petersburg, Sankt-Peterburg, Russian Federation, 197002
      • First Saint Petersburg State Medical University named after academician I.P. Pavlov
• Spain
  • Valencia, Spain, 46015
    • Fundación Oftalmológica del Mediterráneo
  • Andalucia
    • Sevilla, Andalucia, Spain, 41092
      • Cartujavision Oftalmologia
  • Aragon
    • Zaragosa, Aragon, Spain, 50009
      • Hospital Clinico Universitario Lozano Blesa de Zaragoza
  • Catalunya
    • Barcelona, Catalunya, Spain, 8017
      • Institut Català de Retina
    • Barcelona, Catalunya, Spain, 8021
      • Centro de Oftalmologia Barraquer
    • Barcelona, Catalunya, Spain, 8036
      • Hospital Clinic de Barcelona (Hospital Clinic i Provincial)
  • Euskal Autonomia Erkidegoa
    • San Sebastián, Euskal Autonomia Erkidegoa, Spain, 20014
      • Hospital Universitario Donostia, Oftalmalogia
• Turkey
  • Anatolia
    • Ankara, Anatolia, Turkey, 6680
      • Bayındır Kavaklidere Hospital Ophthalmology department
  • Ankara
    • Mamak, Ankara, Turkey, 6620
      • Ankara Üniversitesi Tıp Fakültesi Göz Hastalıkları Anabilim Dalı Vehbi Koç Göz Hastanesi
  • Izmir
    • Bornova, Izmir, Turkey, 35100
      • Ege Universitesi Tip Fakultesi Hastanesi Goz Hastaliklari Anabilim Dali
  • Selcuklu
    • Konya, Selcuklu, Turkey, 42130
      • Selcuk University School of Medicine Ophthalmology department

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Period 1 Open-label Ikervis; 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.	Drug: Open-label Ikervis; NOVA22007, IKERVIS® is a sterile, ophthalmic cationic oil-in-water emulsion containing 1mg/ml CsA.
Experimental: Period 2 Masked Ikervis; 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.	Drug: Masked Ikervis; NOVA22007, IKERVIS® is a sterile, ophthalmic cationic oil-in-water emulsion containing 1mg/ml CsA.
Other: Period 2 Masked Vehicle; 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.	Other: Vehicle Comparator: Masked Vehicle; Vehicle of IKERVIS® - sterile, ophthalmic cationic oil-in-water emulsion containing no active substance.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	Months 3, 6, 9, and 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Corneal Fluorescein Staining (CFS) Score and Change From Baseline by Visit	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.	Baseline, Months 3, 6, 9 and 12

Collaborators and Investigators

• Sponsor: Santen SAS
• Investigators: Study Chair: Jean-Sébastien GARRIGUE, PhD, Santen SAS

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2019
• Primary Completion (Actual): July 14, 2023
• Study Completion (Actual): July 14, 2023

Study Registration Dates

• First Submitted: October 25, 2019
• First Submitted That Met QC Criteria: October 27, 2019
• First Posted (Actual): October 30, 2019

Study Record Updates

• Last Update Posted (Actual): August 28, 2024
• Last Update Submitted That Met QC Criteria: August 26, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Lacrimal Apparatus Diseases; Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Corneal Diseases; Eye Diseases; Dry Eye Syndromes; Keratoconjunctivitis Sicca; Keratitis
• Other Study ID Numbers: NVG14L127

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No