NCT06244316

A Safety and Efficacy Study of 2 Dosing Regimens of Recombinant Human Nerve Growth Factor (rhNGF) Eye Drop Solution Compared With Vehicle in Patients With Dry Eye Disease.

A 4-Week, Phase II, Multicenter, Randomized, Double-Masked, Vehicle-Controlled, Parallel Group Study With 4 Weeks of Follow-Up to Evaluate Safety and Efficacy of a New Formulation of Recombinant Human Nerve Growth Factor (rhNGF) Eye Drop Solution at Two Different Concentrations in Patients With Dry Eye Disease

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 317 (actual)
• Sponsor: Dompé Farmaceutici S.p.A · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Primary objective • To evaluate the efficacy of 5 μg/mL and 10 μg/mL concentrations of the new formulation of rhNGF ophthalmic solution versus vehicle, in order to demonstrate superiority of at least 1 of the concentrations over vehicle in the improvement of ocular symptoms of dry eye in participants with dry eye disease (DED) Key secondary objectives * To evaluate the efficacy of the new formulation of rhNGF ophthalmic solution in increasing the number of participants with improved reflex tear production as compared to vehicle at week 4 * To evaluate the efficacy of the new formulation of rhNGF ophthalmic solution in improving reflex tear production as compared to vehicle at week 4 * To evaluate the efficacy of the new formulation of rhNGF ophthalmic solution in improving ocular surface integrity (corneal epitheliopathy) as compared to vehicle at week 4 Secondary objectives * To evaluate the efficacy of the new formulation of rhNGF ophthalmic solution in improving reflex tear production as compared to vehicle at week 8 * To evaluate the efficacy of the new formulation of rhNGF ophthalmic solution in improving tear film stability as compared to vehicle at weeks 4 and 8 * To evaluate the efficacy of the new formulation of rhNGF ophthalmic solution in improving ocular surface integrity (corneal and conjunctival epitheliopathy) as compared to vehicle at weeks 4 and 8 * To evaluate the efficacy of the new formulation of rhNGF ophthalmic solution in improving the severity and frequency of dry eye symptoms as compared to vehicle at weeks 4 and 8 * To evaluate the efficacy of the new formulation of rhNGF ophthalmic solution in improving dry eye symptoms as compared to vehicle at week 4 * To evaluate the efficacy of the new formulation of rhNGF ophthalmic solution in improving associated symptoms in DED as compared to vehicle at weeks 4 and 8 * To evaluate the efficacy of the new formulation of rhNGF ophthalmic solution in improving the quality of life in participants with DED as compared to vehicle at weeks 4 and 8 * To evaluate the efficacy of the new formulation of rhNGF ophthalmic solution in improving best corrected visual acuity in DED as compared to vehicle at weeks 4 and 8 Safety objectives * To evaluate safety/tolerability of the new formulation of rhNGF ophthalmic solution * To evaluate safety of the new formulation of rhNGF ophthalmic solution * To evaluate tolerability of the new formulation of rhNGF ophthalmic solution

Detailed description

This was a phase 2, multi-center, randomized, double-masked, parallel-arm, vehicle-controlled, dose-finding, clinical study to evaluate the safety and efficacy of 2 concentrations (5 μg/mL and 10 μg/mL) of a reconstituted lyophilized formulation of rhNGF, administered as 1 drop of an ophthalmic solution 3 times a day (TID) in both eyes for 4 weeks in participants with DED. Participants were evaluated at the screening visit (day -12 ± 2; visit 1), baseline (day 1; visit 2), week 2 (day 13 ± 1; visit 3), week 4 end of treatment (EOT; day 28 ± 1; visit 4), and week 8 end of follow-up and end of study (EOS; day 56 ± 2; visit 5). At the screening visit (visit 1), participants who signed informed consent and met all eligibility criteria were enrolled and instructed to discontinue all topical ophthalmic medications; during the run-in period, they were only allowed to use investigational product (vehicle) ophthalmic solution provided by the sponsor. The first eye drop of the vehicle was applied to both eyes of participants at the site by the investigator during visit 1. Participants were instructed on how to prepare the investigational product (vehicle) daily at home and then how to self-administer 1 drop TID in both eyes. A Patient Diary for the run-in phase was supplied to the participant. At the conclusion of the day 1 baseline visit (visit 2), participants still meeting all eligibility criteria were randomly assigned 1:1:1 to a 4-week treatment regimen of investigational product (vehicle, or rhNGF \[5 μg/mL or 10 μg/mL\]), administered as follows: * 1 drop of rhNGF ophthalmic solution at 5 μg/mL in each eye TID, at approximately 6-hour intervals, for 4 weeks * 1 drop of rhNGF ophthalmic solution at 10 μg/mL in each eye TID, at approximately 6-hour intervals, for 4 weeks * 1 drop of vehicle in each eye, TID, at approximately 6-hour intervals, for 4 weeks. Eligible participants were also dispensed a 2-week supply of the investigational product (vehicle or rhNGF) to administer at home between visits 2 and 3. They received another 2-week supply during visit 3. A Patient Diary for recording the treatment phase was supplied to the participant. At visit 2 (baseline visit) a study eye was determined. Namely, the study eye was the worse eye. Assuming that all inclusion/exclusion criteria were met in both eyes, the worse eye (study eye) was determined based on the lower Schirmer-I (without anesthesia) score. If the Schirmer-I score was identical in both eyes, the study eye was determined based on the worse score for corneal and conjunctival NEI staining (total score for corneal staining followed by total score for conjunctival). If the staining score was identical in both eyes, then the right eye was assigned as the study eye. Participants who prematurely discontinued the treatment (for any reason) were asked to complete the remaining assessments planned by the protocol and received commercially available preservative-free AT, TID, provided by the sponsor. In case of withdrawal from the study, participants were asked to complete the assessment expected for visit 4 as an Early Exit Visit. Following the completion of the treatment period, participants were followed up for an additional 4 weeks and were evaluated at 8 weeks (visit 5). During the 4-week follow-up period, no treatment was allowed except for commercially available preservative free AT TID provided by the sponsor. A Patient Diary for the follow-up period was supplied to the patient.

Conditions

• Dry Eye Disease

Interventions

Type	Name	Description
DRUG	rhNGF 5 μg/mL	1 drop of rhNGF ophthalmic solution at 5 μg/mL in each eye TID, at approximately 6-hour intervals, for 4 weeks of treatment.
DRUG	rhNGF 10 μg/mL	1 drop of rhNGF ophthalmic solution at 10 μg/mL in each eye TID, at approximately 6-hour intervals, for 4 weeks of treatment.
DRUG	Vehicle (Placebo solution)	Eye drop solution, containing no rhNGF. 1 drop of vehicle in each eye TID at approximately 6-hour intervals, for 4 weeks of treatment.

Timeline

• Start date: 2024-01-22
• Primary completion: 2024-12-04
• Completion: 2024-12-04
• First posted: 2024-02-06
• Last updated: 2026-02-13
• Results posted: 2026-02-13

Locations

14 sites across 2 countries: United States, Italy

Regulatory

• FDA-regulated drug study