REC 0/0559 Eye Drops for Treatment of Moderate and Severe Neurotrophic Keratitis in Adult Patients

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

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.

Study Overview

• Status: Completed
• Conditions: Neurotrophic Keratitis
• Intervention / Treatment: Drug: Udonitrectag; Other: Vehicle

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).

• Study Type: Interventional
• Enrollment (Actual): 108
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Dijon, France, 21000
    • Dijon University Hospital CHU Dijon
  • Paris, France
    • Hôpital Fondation Adolphe de Rothschild
  • Paris, France, 75014
    • CHU Paris Centre - Hôpital Cochin
  • Paris, France
    • Hôpital Universitaire Necker
• Germany
  • Düsseldorf, Germany, 40225
    • Hospital Eye University of Duesseldorf
  • Frankfurt, Germany, 60590
    • Universitaetsklinikum Frankfurt
  • Homburg, Germany
    • Saarland University Medical Center
  • Koeln, Germany, 50924
    • Uniklinik Koeln
  • Mainz, Germany, 55131
    • Universitätsmedizin der Johannes Gutenberg-Universität Mainz
  • Bavaria
    • Munich, Bavaria, Germany, 80336
      • Ludwig-Maximilians-Universitaet Muenchen LMU - Augenklinik
• Hungary
  • Budapest, Hungary
    • Semmelweis University, Dept. of Ophthalmology
  • Pécs, Hungary
    • University of Pecs - Dpt of Ophthalmology
  • Vas County
    • Szombathely, Vas County, Hungary, 9700
      • Markusovszky University Teaching Hospital
• Italy
  • Bari, Italy, 70124
    • Azienda Universitaria Ospedaliera Consorziale - Policlinico Bari Clinica Oculistica
  • Bologna, Italy, 40138
    • DIMES Universit di Bologna
  • Firenze, Italy, 50134
    • Azienda Ospedaliero-Universitaria Careggi
  • Forlì, Italy
    • Ospedali Privato
  • Genova, Italy, 16132
    • Azienda Ospedaliera Universitaria San Martino
  • Messina, Italy
    • Azienda Ospedaliera Universitaria Policlinico Gaetano Martino
  • Milano, Italy, 20157
    • Ospedale Luigi Sacco
  • Roma, Italy, 00133
    • Fondazione PTV - Policlinico Tor Vergata
  • Calabria
    • Germaneto, Calabria, Italy, 88100
      • Università Magna Grecia di Catanzaro
• Spain
  • Barakaldo, Spain, 48903
    • Hospital de Cruces
  • Barcelona, Spain
    • Centro de Oftalmologia Barraquer
  • Barcelona, Spain, 08035
    • Instituto Microcirugia Ocular IMO
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Sevilla, Spain
    • Cartuja Vision - Centro de Servicios Oftlamologicos
  • Asturias
    • Oviedo, Asturias, Spain, 33012
      • Instituto Oftalmologico Fernandez-Vega
• United Kingdom
  • Glasgow, United Kingdom, G75 8RG
    • University Hospital Hairmyres
  • London, United Kingdom
    • Moorfields Eye Hospital NHS Foundation Trust
  • Southampton, United Kingdom, SO16 6YD
    • Southampton General Hospital
  • Mersey
    • Liverpool, Mersey, United Kingdom, L7 8XP
      • Royal Liverpool University Hospital - St Paul's Clinical Eye Research Centre
• United States
  • Florida
    • Crystal River, Florida, United States, 34429-8722
      • Nature Coast Clinical Research
    • Gainesville, Florida, United States, 32605
      • University of Florida
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland School of Medicine UMSOM
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • University of Michigan - Kellogg Eye Center
  • New York
    • New York, New York, United States, 10003
      • Mt. Sinai New York Eye and Ear Infirmary
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37215
      • Toyos Clinic
  • Texas
    • Houston, Texas, United States, 77025
      • Houston Eye Associates HEA - Gramercy Location
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • University of Wisconsin-Madison

Participation Criteria

Eligibility Criteria

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

Description

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™

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose 1 - 0.5 µg/day; Dose of study drug per day: 0.5 µg/day Study drug concentration: 5 µg/mL MT8 given 1 drop QID	Drug: Udonitrectag; Eye drop solution in single dose unit.; Other Names: REC 0/0559; Other: Vehicle; Eye drop solution with no active substance in single dose unit.
Experimental: Dose 2 - 2.5 µg/day; Dose of study drug per day: 2.5 µg/day Study drug concentration: 25 µg/mL MT8 given 1 drop QID	Drug: Udonitrectag; Eye drop solution in single dose unit.; Other Names: REC 0/0559; Other: Vehicle; Eye drop solution with no active substance in single dose unit.
Experimental: Dose 3 - 5 µg/day; Dose of study drug per day: 5 µg/day Study drug concentration: 50 µg/mL MT8 given 1 drop QID	Drug: Udonitrectag; Eye drop solution in single dose unit.; Other Names: REC 0/0559; Other: Vehicle; Eye drop solution with no active substance in single dose unit.
Placebo Comparator: Vehicle; Dose of study drug per day: 0 µg/day Study drug concentration: Vehicle given 1 drop QID	Other: Vehicle; Eye drop solution with no active substance in single dose unit.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Corneal Healing	The primary endpoint of this study is the percentage of patients achieving complete corneal healing of PED or corneal ulcer at Week 8, defined as no corneal fluorescein staining in the area of the PED or corneal ulcer as assessed by an independent central reading centre.	At week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual Acuity	Percentage of patients who achieve a 5-, 10-, and 15-letter mean improvement in best corrected distance visual acuity (BCDVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) chart at Week 8 compared to baseline (in all patients and in patients with a central location of the PED or corneal ulcer, respectively).	At week 8

Collaborators and Investigators

• Sponsor: Recordati Rare Diseases
• Collaborators: Syneos Health

Study record dates

Study Major Dates

• Study Start (Actual): October 13, 2020
• Primary Completion (Actual): April 29, 2024
• Study Completion (Actual): April 29, 2024

Study Registration Dates

• First Submitted: February 17, 2020
• First Submitted That Met QC Criteria: February 17, 2020
• First Posted (Actual): February 19, 2020

Study Record Updates

• Last Update Posted (Actual): May 14, 2025
• Last Update Submitted That Met QC Criteria: April 28, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Corneal Diseases; Keratitis
• Other Study ID Numbers: REC0559-B-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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