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

Neurotrophic Keratitis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04276558
• Other study ID #: REC0559-B-001
• Status: Completed
• Phase: Phase 2
• Start date: October 13, 2020
• Est. completion date: April 29, 2024

Study information

• Verified date: May 2024
• Source: Recordati Rare Diseases
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 108
• Est. completion date: April 29, 2024
• Est. primary completion date: April 29, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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™

Related Conditions & MeSH terms

• Keratitis
• Neurotrophic Keratitis

Intervention

Drug:
• Udonitrectag
Eye drop solution in single dose unit.

Other:
• Vehicle
Eye drop solution with no active substance in single dose unit.

Locations

Country	Name	City	State
France	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
Germany	Hospital Eye University of Duesseldorf	Düsseldorf
Germany	Universitaetsklinikum Frankfurt	Frankfurt
Germany	Saarland University Medical Center	Homburg
Germany	Uniklinik Koeln	Koeln
Germany	UNIVERSITÄTSMEDIZIN der Johannes Gutenberg-Universität Mainz	Mainz
Germany	Ludwig-Maximilians-Universitaet Muenchen LMU - Augenklinik	Munich	Bavaria
Hungary	Semmelweis University, Dept. of Ophthalmology	Budapest
Hungary	University of Pecs - Dpt of Ophthalmology	Pécs
Hungary	Markusovszky University Teaching Hospital	Szombathely	Vas County
Italy	Azienda Universitaria Ospedaliera Consorziale - Policlinico Bari Clinica Oculistica	Bari
Italy	DIMES Universit di Bologna	Bologna
Italy	Azienda Ospedaliero-Universitaria Careggi	Firenze
Italy	Ospedali Privato	Forlì
Italy	Azienda Ospedaliera Universitaria San Martino	Genova
Italy	Università Magna Grecia di Catanzaro	Germaneto	Calabria
Italy	Azienda Ospedaliera Universitaria Policlinico Gaetano Martino	Messina
Italy	Ospedale Luigi Sacco	Milano
Italy	Fondazione PTV - Policlinico Tor Vergata	Roma
Spain	Hospital de Cruces	Barakaldo
Spain	Centro de Oftalmologia Barraquer	Barcelona
Spain	Instituto Microcirugia Ocular IMO	Barcelona
Spain	Hospital Clinico San Carlos	Madrid
Spain	Instituto Oftalmologico Fernandez-Vega	Oviedo	Asturias
Spain	Cartuja Vision - Centro de Servicios Oftlamologicos	Sevilla
United Kingdom	University Hospital Hairmyres	Glasgow
United Kingdom	Royal Liverpool University Hospital - St Paul's Clinical Eye Research Centre	Liverpool	Mersey
United Kingdom	Moorfields Eye Hospital NHS Foundation Trust	London
United Kingdom	Southampton General Hospital	Southampton
United States	University of Michigan - Kellogg Eye Center	Ann Arbor	Michigan
United States	University of Maryland School of Medicine UMSOM	Baltimore	Maryland
United States	Nature Coast Clinical Research	Crystal River	Florida
United States	University of Florida	Gainesville	Florida
United States	Houston Eye Associates HEA - Gramercy Location	Houston	Texas
United States	University of Wisconsin-Madison	Madison	Wisconsin
United States	Toyos Clinic	Nashville	Tennessee
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

Sponsors (2)

Lead Sponsor	Collaborator
Recordati Rare Diseases	Syneos Health

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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