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

NCT04144413 | Completed Phase 3 Results

• 1 other identifier: NVG14L127
• Study Type: interventional
• Target: 350
• Locations: 7 countries
• Sites: 45

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

Conditions

Dry Eye Disease With Severe Keratitis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Corneal Fluorescein Staining (CFS) Score and Change From Baseline by Visit

  Baseline, Months 3, 6, 9 and 12

Study Arms (3)

Period 1 Open-label Ikervis

EXPERIMENTAL

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

Period 2 Masked Ikervis

EXPERIMENTAL

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

Period 2 Masked Vehicle

OTHER

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

Interventions

Open-label Ikervis DRUG

NOVA22007, IKERVIS® is a sterile, ophthalmic cationic oil-in-water emulsion containing 1mg/ml CsA.

Period 1 Open-label Ikervis

Masked Ikervis DRUG

NOVA22007, IKERVIS® is a sterile, ophthalmic cationic oil-in-water emulsion containing 1mg/ml CsA.

Period 2 Masked Ikervis

Vehicle Comparator: Masked Vehicle OTHER

Vehicle of IKERVIS® - sterile, ophthalmic cationic oil-in-water emulsion containing no active substance.

Period 2 Masked Vehicle

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Santen SAS: lead

Study Sites (45)

Fakultni Nemocnice Ostrava, Oční Klinika

Ostrava, Moravskoslezský kraj, 70800, Czechia

Location

University Hospital Hradec Kralove

Hradec Králové, Nový Hradec Králové, 50005, Czechia

Location

Ocni klinika OFTEX

Pardubice, Pardubický kraj, 53002, Czechia

Location

MEDOKO s.r.o.

Prague, Prague, 10800, Czechia

Location

Axon clinical s.r.o.

Prague, Prague, 15000, Czechia

Location

Fakultní Nemocnice Brno

Brno, South Moravian, 62500, Czechia

Location

Nemocnice Teplice, Ocni Oddeleni

Teplice, Ústecký kraj, 41505, Czechia

Location

Masarykova nemocnice, Ocni oddeleni

Ústí nad Labem, Ústecký kraj, 4001, Czechia

Location

Hospices Civils de Lyon - Hopital de la Croix-Rousse

Lyon, Auvergne-Rhône-Alpes, 69317, France

Location

Hopitaux Universitaires Paris-Sud - Hopital Bicetre

Le Kremlin-Bicêtre, Île-de-France Region, 94270, France

Location

Hôpital des Quinze-Vingts

Paris, Île-de-France Region, 75012, France

Location

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

Paris, Île-de-France Region, 75877, France

Location

Universita degli Studi di Milano - Clinica Oculistica I

Milan, Lombardy, 20122, Italy

Location

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

Milan, Lombardy, 20123, Italy

Location

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

Milan, Lombardy, 20142, Italy

Location

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

Milan, Lombardy, 20157, Italy

Location

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

Pavia, Lombardy, 27100, Italy

Location

Azienda Ospedaliera Universitaria Policlinico Gaetano Martino - Messina

Messina, Sicily, 98128, Italy

Location

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

Padua, Veneto, 35128, Italy

Location

Niepubliczny Zaklad Opieki Zdrowotnej Oko-Laser

Krakow, Lesser Poland Voivodeship, 30644, Poland

Location

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

Lublin, Lublin Voivodeship, 20079, Poland

Location

Gabinet Okulistyczny Prof. Edward Wylęgała

Katowice, Silesian Voivodeship, 40594, Poland

Location

Uniwersyteckie Centrum Kliniczne Śląskiego Uniwersytetu Medycznego w Katowicach

Katowice, Silesian Voivodeship, 40952, Poland

Location

Retina Szpital Okulistyczny

Warsaw, Warszawskie, 1364, Poland

Location

Uniwersytecki Szpital Kiliniczny IM. Jana Milkulicza-Radeckiego we Wroclawiu

Wroclaw, Wrocławiu, 50556, Poland

Location

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

Cheboksary, Chuvashskaya Respublika, 428028, Russia

Location

Ivanovo Regional Clinical Hospital

Ivanov, Ivanovo Oblast, 153040, Russia

Location

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

Moscow, Moscow, 111398, Russia

Location

NMRC ISTC Eye Microsurgery n. a. Fyodorov - Moscow

Moscow, Moscow, 126486, Russia

Location

Saint Petersburg State Pediatric Medical University

Saint Petersburg, Sankt-Peterburg, 194100, Russia

Location

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

Saint Petersburg, Sankt-Peterburg, 197002, Russia

Location

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

Novosibirsk, 630120, Russia

Location

GBOU VPO Omsk State Medical Academy, Ophthalmology Department

Omsk, 644024, Russia

Location

Saratov Railway Clinic

Saratov, 41004, Russia

Location

Cartujavision Oftalmologia

Seville, Andalusia, 41092, Spain

Location

Hospital Clinico Universitario Lozano Blesa de Zaragoza

Zaragoza, Aragon, 50009, Spain

Location

Hospital Universitario Donostia, Oftalmalogia

Donostia / San Sebastian, Basque Country, 20014, Spain

Location

Institut Catala de Retina

Barcelona, Catalonia, 8017, Spain

Location

Centro de Oftalmología Barraquer

Barcelona, Catalonia, 8021, Spain

Location

Hospital Clinic de Barcelona (Hospital Clinic i Provincial)

Barcelona, Catalonia, 8036, Spain

Location

Fundación Oftalmológica del Mediterráneo

Valencia, 46015, Spain

Location

Bayındır Kavaklidere Hospital Ophthalmology department

Ankara, Anatolia, 6680, Turkey (Türkiye)

Location

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

Mamak, Ankara, 6620, Turkey (Türkiye)

Location

Ege Universitesi Tip Fakultesi Hastanesi Goz Hastaliklari Anabilim Dali

Bornova, İzmir, 35100, Turkey (Türkiye)

Location

Selcuk University School of Medicine Ophthalmology department

Konya, Selcuklu, 42130, Turkey (Türkiye)

Location

Results Point of Contact

• Title: Director of R&D Quality Management
• Organization: Santen Inc

evelyn.chikere@santen.com

15106851794

Study Officials

• Jean-Sébastien GARRIGUE, PhD

  Santen SAS

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: October 25, 2019
• First Posted: October 30, 2019
• Study Start: May 31, 2019
• Primary Completion: July 14, 2023
• Study Completion: July 14, 2023
• Last Updated: August 28, 2024
• Results First Posted: August 28, 2024

Record last verified: 2024-08

Locations

FR (4); PL (6); ES (7); CZ (8); IT (7); RU (9); TU (4)