Clinical trial NCT04276558: REC 0/0559 Eye Drops for Treatment of Moderate and Severe Neurotrophic Keratitis in Adult Patients
Official title: Efficacy, Safety and Pharmacokinetics of 3 Doses of REC 0/0559 Eye Drops for the Treatment of Stage 2 (Moderate) and 3 (Severe) Neurotrophic Keratitis in Adult Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neurotrophic Keratitis
Lead sponsor: Recordati Rare Diseases
Sponsor class: INDUSTRY
Collaborators: name: Syneos Health
First posted: 2020-02-19
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: The study will have an initial period of dose escalation followed by a parallel recruitment period. Randomisation in the first 24 patients will be sequential and after, patients will be randomised to all 4 treatment arms.
Primary purpose: TREATMENT

Brief summary: A phase 2 study, aiming to evaluate the efficacy, safety and pharmacokinetics of REC 0/0559 in treatment of Neurotrophic Keratitis in Adult Patient in Europe and United States of America.

Detailed description: This was a Phase 2, international, multicentre, dose-ranging, double-masked, randomised, parallel-group, vehicle-controlled study designed to evaluate 3 different doses of REC 0/0559 vs vehicle in patients with Stage 2 and Stage 3 neurotrophic keratitis (NK).

Eligibility criteria: Inclusion Criteria:

1. Have read, understood, and signed the informed consent form (ICF).
2. Be a male or female aged ≥18 years at the time of ICF signature.
3. Have stage 2 moderate (PED) or stage 3 severe (corneal ulcer) NK involving only 1 eye (study eye) and of at least 2 weeks duration. Patients with Stage 1 NK in the fellow eye can be enrolled.

   for the study eye
4. Have no objective clinical evidence of improvement in the PED or corneal ulceration within the 2 weeks before the screening visit despite use of conventional non-surgical treatment (eg, nonpreserved ocular lubricants, nonpreserved topical antibiotics, oral doxycycline, patching, serum tears, and/or therapeutic contact lenses) as determined by the investigator's or referring physician's medical record.
5. Have decreased corneal sensitivity (≤ 4 cm using the Cochet-Bonnet aesthesiometer) within the area of the PED or corneal ulcer and outside of the area of the defect in at least one corneal quadrant.
6. Have a BCDVA score ≤ 75 ETDRS letters in the study eye, due to NK.

Exclusion Criteria:

1. Have participated in any clinical trial with an investigational drug/device within 2 months before the Screening Visit and throughout the study duration.
2. Have a known hypersensitivity to one of the components of the study drug or procedural medications (eg, fluorescein), including to a compound chemically related to MT8
3. Have a presence or history of any ocular or systemic disorder or condition that might hinder the efficacy of the study treatment or its evaluation, could possibly interfere with the interpretation of study results, or could be judged by the investigator to be incompatible with the study visit schedule or conduct (eg, progressive or degenerative corneal or retinal conditions, lagophthalmos, uveitis, optic neuritis, poorly controlled diabetes, autoimmune disease, systemic infection, neoplastic diseases), or that may compromise the safety of the patient.
4. Have a significant history of alcohol abuse or drug/solvent abuse
5. Be unwilling to comply with any study assessments or procedures.
6. Be a woman who is pregnant, nursing or planning a pregnancy.
7. Be a woman of childbearing potential not using a highly effective method of birth control.
8. Be a male patient who is not permanently sterile and who is not willing to use condoms during the study and for 4 weeks after the end of study treatment.

   For the study eye:
9. Have any active ocular infection (bacterial, viral, fungal or protozoal) or active inflammation not related to NK in the study eye.
10. Have any other ocular disease requiring topical ocular treatment in the study eye during the course of the study treatment period, except for glaucoma if treated by preservative-free eye drop (single-agent treatment, once daily, stable regimen 4 weeks before screening and during the study),
11. Receive topical ophthalmological treatments other than the study drug provided by the study Sponsor and the treatments allowed by the study protocol (eg, preservative-free artificial tears; preservative-free eye drop (single-agent treatment, once daily, stable regimen 4 weeks before screening and during the study) for glaucoma; topical antibiotics; other than tetracycline).
12. Have severe blepharitis and/or severe meibomian gland disease in the study eye.
13. Have severe vision loss in the study eye with no potential for visual improvement in the opinion of the investigator as a result of the study treatment.
14. Have evidence of corneal ulceration/melting involving the posterior third of the corneal stroma, or perforation in the study eye.
15. Have a history of any ocular surgery (including laser or refractive surgical procedures) within 3 months before the Screening Visit in the study eye. An exception to the preceding statement will be allowed if the ocular surgery is considered to be the cause of the Stage 2 or 3 NK.
16. Have a history of corneal transplantation in the study eye, except if performed to treat NK and at least 6 months prior screening.
17. Have had prior surgical procedures for the treatment of NK (eg, tarsorrhaphy, conjunctival flap, etc.) except AMT, if at least 2 wks after the membrane has disappeared within the area of the PED or corneal ulcer (and at least 6 weeks after the procedure) in the study eye.
18. Use therapeutic contact lenses or wear contact lenses for refractive correction during the study treatment periods in the eye(s) with NK.
19. Have an anticipated need for punctal occlusion during the study treatment period. Patients with punctal occlusion or punctal plugs inserted before the study are eligible for enrolment provided that the punctal occlusion is maintained during the study.
20. Have an uncontrolled glaucoma at the Screening Visit. (Patients suffering from glaucoma requiring ophthalmic drops for topical treatment at the Screening Visit or during the study are not eligible, except if the ophthalmic drops is a preservative-free treatment administered maximum once daily as a single-agent treatment and at a stable regimen 4 weeks before screening and at the same dose during the study. Patients treated with oral intraocular pressure-lowering drugs at the Screening Visit and during the study may be enrolled if their glaucoma status is assessed as stable and controlled.

    For the fellow eye
21. Have Stage 2 or 3 NK or perforation.

    For any eye:
22. Have a history of ocular cancer.
23. Have had prior treatment with Oxervate™

Primary outcomes:
measure: Corneal Healing
timeFrame: At week 8
Secondary outcomes:
measure: Visual Acuity
timeFrame: At week 8
Other outcomes:
Locations:
city: Crystal River
country: United States
facility: Nature Coast Clinical Research
state: Florida
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Baltimore
country: United States
facility: University of Maryland School of Medicine UMSOM
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan - Kellogg Eye Center
state: Michigan
city: New York
country: United States
facility: Mt. Sinai New York Eye and Ear Infirmary
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center
state: North Carolina
city: Nashville
country: United States
facility: Toyos Clinic
state: Tennessee
city: Houston
country: United States
facility: Houston Eye Associates HEA - Gramercy Location
state: Texas
city: Madison
country: United States
facility: University of Wisconsin-Madison
state: Wisconsin
city: Dijon
country: France
facility: Dijon University Hospital CHU Dijon
city: Paris
country: France
facility: CHU Paris Centre - Hôpital Cochin
city: Paris
country: France
facility: Hôpital Fondation Adolphe de Rothschild
city: Paris
country: France
facility: Hôpital Universitaire Necker
city: Munich
country: Germany
facility: Ludwig-Maximilians-Universitaet Muenchen LMU - Augenklinik
state: Bavaria
city: Düsseldorf
country: Germany
facility: Hospital Eye University of Duesseldorf
city: Frankfurt
country: Germany
facility: Universitaetsklinikum Frankfurt
city: Homburg
country: Germany
facility: Saarland University Medical Center
city: Koeln
country: Germany
facility: Uniklinik Koeln
city: Mainz
country: Germany
facility: UNIVERSITÄTSMEDIZIN der Johannes Gutenberg-Universität Mainz
city: Szombathely
country: Hungary
facility: Markusovszky University Teaching Hospital
state: Vas County
city: Budapest
country: Hungary
facility: Semmelweis University, Dept. of Ophthalmology
city: Pécs
country: Hungary
facility: University of Pecs - Dpt of Ophthalmology
city: Germaneto
country: Italy
facility: Università Magna Grecia di Catanzaro
state: Calabria
city: Bari
country: Italy
facility: Azienda Universitaria Ospedaliera Consorziale - Policlinico Bari Clinica Oculistica
city: Bologna
country: Italy
facility: DIMES Universit di Bologna
city: Firenze
country: Italy
facility: Azienda Ospedaliero-Universitaria Careggi
city: Forlì
country: Italy
facility: Ospedali Privato
city: Genova
country: Italy
facility: Azienda Ospedaliera Universitaria San Martino
city: Messina
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Gaetano Martino
city: Milano
country: Italy
facility: Ospedale Luigi Sacco
city: Roma
country: Italy
facility: Fondazione PTV - Policlinico Tor Vergata
city: Oviedo
country: Spain
facility: Instituto Oftalmologico Fernandez-Vega
state: Asturias
city: Barakaldo
country: Spain
facility: Hospital de Cruces
city: Barcelona
country: Spain
facility: Instituto Microcirugia Ocular IMO
city: Barcelona
country: Spain
facility: Centro de Oftalmologia Barraquer
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Sevilla
country: Spain
facility: Cartuja Vision - Centro de Servicios Oftlamologicos
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital - St Paul's Clinical Eye Research Centre
state: Mersey
city: Glasgow
country: United Kingdom
facility: University Hospital Hairmyres
city: London
country: United Kingdom
facility: Moorfields Eye Hospital NHS Foundation Trust
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
References: