Phase 2 study of REC 0/0559 eye drops to treat Neurotrophic Keratitis
Research type
Research Study
Full 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
IRAS ID
276465
Contact name
Frank Larkin
Contact email
Sponsor organisation
Recordati Rare Diseases
Eudract number
2019-002475-34
Clinicaltrials.gov Identifier
139657, IND number
Duration of Study in the UK
1 years, 4 months, 1 days
Research summary
Research Summary:
Neurotrophic keratitis (NK) is a rare degenerative corneal condition characterised by decreased corneal sensitivity and poor healing. This disorder leaves the cornea susceptible to injury and decreases reflex tearing; breakdown of the corneal epithelium (tissue covering the front of the cornea) can lead to ulceration, infection, melting, and perforation. It is classified into progressive stages 1-3, and conventional treatment depends on the stage.However despite the availability of current treatments healing response in NK patients remains difficult to obtain, visual outcomes are poor. Available nonclinical and clinical data indicate that recombinant human nerve growth factor eye drops can be beneficial but may not be well tolerated, with the potential for adverse events. Based on these data it appears the compound MT8 could be efficacious in treatment of NK. The objective of this study is to demonstrate the safety and efficacy of REC 0/0559 (eye drops prepared using MT8) and to select the most appropriate dose.
This study is an international multicentre parallel-group dose-ranging Phase 2 trial with a double-masked randomised ‘vehicle’ (placebo) controlled design. It will evaluate 3 different doses of REC 0/0559 versus vehicle in patients with Stage 2 and Stage 3 NK. Following initial screening and informed consent, the first 24 eligible participants will be randomly enrolled into one of three sequential escalating dose cohorts (or vehicle), 8 per cohort.
After completion and review of the dose escalation stage, initial and further participants (≥18 years male or female, total approximately 108) will be enrolled onto an 8 week treatment stage followed by a 4 week follow-up period.
Lay summary of study results:
Neurotrophic keratitis (NK) is a degenerative eye condition where
the cornea (clear part of the eye) does not heal properly due to nerve damage. REC 0/0559 is a
solution provided in the form of eye drops which was tested and compared to a placebo (treatment
with no active drug) to see if it could improve corneal damage as a result of NK. It was given as 1
drop 4 times a day at 5, 25, and 50 μg/mL (micrograms per milliletre) for 8 weeks. Results showed
that treatment did not show clinical benefit at Week 8. The proportion of healed patients at Week 8
as assessed by an independent group was 33.3%, 19.2%, 19.2%, and 34.5% for the 0.5 μg/day
group, the 2.5 μg/day group, the 5.0 μg/day group, and the placebo group, respectively. This
difference was not statistically significant between the REC 0/0559 groups and the placebo group.
Similar results were seen for the key secondary objective of the study that the percentage of
patients achieving complete corneal healing of Persistent Epithelial defects (PED; consistent
damage to the top layer of the cornea) or corneal ulcer at Week 8, were also not clinically
significant versus the placebo group. No statistically significant treatment differences were
observed for the other main secondary objectives defined in the protocol as well for this study.
Participants using REC 0/0559 had more eye-related Adverse Events (AE; Side effects) than the
placebo group. Most of the AEs however, were mild or moderate in severity and reversible.
Furthermore, the AEs were mostly related to the administration of the eye drops and were
temporary, indicating that the REC 0/0559 was generally well tolerated and the safety profile was
manageable.REC name
London - West London & GTAC Research Ethics Committee
REC reference
20/LO/0316
Date of REC Opinion
15 May 2020
REC opinion
Further Information Favourable Opinion