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

NCT ID: NCT04276558

Last Updated: 2025-05-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 108 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-13
• Study Completion Date: 2024-04-29

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).

Conditions

Neurotrophic Keratitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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

Group Type: EXPERIMENTAL

Udonitrectag

Intervention Type: DRUG

Eye drop solution in single dose unit.

Vehicle

Intervention Type: OTHER

Eye drop solution with no active substance in single dose unit.

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

Group Type: EXPERIMENTAL

Udonitrectag

Intervention Type: DRUG

Eye drop solution in single dose unit.

Vehicle

Intervention Type: OTHER

Eye drop solution with no active substance in single dose unit.

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

Group Type: EXPERIMENTAL

Udonitrectag

Intervention Type: DRUG

Eye drop solution in single dose unit.

Vehicle

Intervention Type: OTHER

Eye drop solution with no active substance in single dose unit.

Vehicle

Dose of study drug per day: 0 µg/day Study drug concentration: Vehicle given 1 drop QID

Group Type: PLACEBO_COMPARATOR

Vehicle

Intervention Type: OTHER

Eye drop solution with no active substance in single dose unit.

Interventions

Udonitrectag

Eye drop solution in single dose unit.

Intervention Type: DRUG

Vehicle

Eye drop solution with no active substance in single dose unit.

Intervention Type: OTHER

Other Intervention Names

REC 0/0559

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™

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Syneos Health

OTHER

Sponsor Role: collaborator

Recordati Rare Diseases

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Nature Coast Clinical Research

Crystal River, Florida, United States

University of Florida

Gainesville, Florida, United States

University of Maryland School of Medicine UMSOM

Baltimore, Maryland, United States

University of Michigan - Kellogg Eye Center

Ann Arbor, Michigan, United States

Mt. Sinai New York Eye and Ear Infirmary

New York, New York, United States

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, United States

Toyos Clinic

Nashville, Tennessee, United States

Houston Eye Associates HEA - Gramercy Location

Houston, Texas, United States

University of Wisconsin-Madison

Madison, Wisconsin, United States

Dijon University Hospital CHU Dijon

Dijon, , France

CHU Paris Centre - Hôpital Cochin

Paris, , France

Hôpital Fondation Adolphe de Rothschild

Paris, , France

Hôpital Universitaire Necker

Paris, , France

Ludwig-Maximilians-Universitaet Muenchen LMU - Augenklinik

Munich, Bavaria, Germany

Uniklinik Koeln

Cologne, , Germany

Hospital Eye University of Duesseldorf

Düsseldorf, , Germany

Universitaetsklinikum Frankfurt

Frankfurt, , Germany

Saarland University Medical Center

Homburg, , Germany

UNIVERSITÄTSMEDIZIN der Johannes Gutenberg-Universität Mainz

Mainz, , Germany

Markusovszky University Teaching Hospital

Szombathely, Vas County, Hungary

Semmelweis University, Dept. of Ophthalmology

Budapest, , Hungary

University of Pecs - Dpt of Ophthalmology

Pécs, , Hungary

Università Magna Grecia di Catanzaro

Germaneto, Calabria, Italy

Azienda Universitaria Ospedaliera Consorziale - Policlinico Bari Clinica Oculistica

Bari, , Italy

DIMES Universit di Bologna

Bologna, , Italy

Azienda Ospedaliero-Universitaria Careggi

Florence, , Italy

Ospedali Privato

Forlì, , Italy

Azienda Ospedaliera Universitaria San Martino

Genova, , Italy

Azienda Ospedaliera Universitaria Policlinico Gaetano Martino

Messina, , Italy

Ospedale Luigi Sacco

Milan, , Italy

Fondazione PTV - Policlinico Tor Vergata

Roma, , Italy

Instituto Oftalmologico Fernandez-Vega

Oviedo, Principality of Asturias, Spain

Hospital de Cruces

Barakaldo, , Spain

Instituto Microcirugia Ocular IMO

Barcelona, , Spain

Centro de Oftalmologia Barraquer

Barcelona, , Spain

Hospital Clinico San Carlos

Madrid, , Spain

Cartuja Vision - Centro de Servicios Oftlamologicos

Seville, , Spain

Royal Liverpool University Hospital - St Paul's Clinical Eye Research Centre

Liverpool, Mersey, United Kingdom

University Hospital Hairmyres

Glasgow, , United Kingdom

Moorfields Eye Hospital NHS Foundation Trust

London, , United Kingdom

Southampton General Hospital

Southampton, , United Kingdom

Countries

United States; France; Germany; Hungary; Italy; Spain; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

REC0559-B-001

Identifier Type: -

Identifier Source: org_study_id