Cenegermin Ophthalmic Solution for the Treatment of Persistent Corneal Epithelial Defect: Phase 3 Randomized, Double-Masked, Vehicle-Controlled Study
- Trial ID
- 2025-523443-35-00
- Protocol
- NGF-PCED-301
- Sponsor
- Dompe' Farmaceutici S.p.A.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the efficacy of cenegermin ophthalmic solution compared to a vehicle in inducing complete healing of a persistent corneal epithelial defect (PCED) after 4 weeks of treatment. This assessment is clinically relevant to determine the regenerative potential of recombinant human nerve growth factor in resolving ocular surface defects.
The secondary objectives include:
- Evaluating the efficacy of cenegermin ophthalmic solution compared to vehicle in improving the PCED from baseline at 4 weeks and 8 weeks of treatment.
- Evaluating the efficacy of cenegermin ophthalmic solution compared to vehicle in inducing complete healing of the PCED after 8 weeks of treatment.
Participants
This clinical trial involves 124 participants diagnosed with Persistent Corneal Epithelial Defect (PCED). The study population consists of both male and female patients aged 18 years or older. Inclusion requires a PCED in the study eye measuring at least 1.0 mm in greatest diameter with a duration of at least 14 days. Eligible individuals must have a condition that is refractory to one or more conventional nonsurgical treatments, such as ocular lubricants, bandage contact lenses, or the discontinuation of preserved medications. Participants may continue stable doses of most ophthalmic medications for other ocular conditions for at least 30 days. The use of prophylactic antibiotics in the study eye is permitted if therapy was initiated prior to enrollment.
Plans and Procedures
This Phase 3, multicenter, randomized, double-masked, vehicle-controlled, parallel group study is designed to evaluate the safety and efficacy of cenegermin ophthalmic solution compared to a vehicle in participants with persistent corneal epithelial defect (PCED). The primary objective is to assess the induction of complete epithelial healing at week 4 and its maintenance at week 8. Secondary endpoints include the percentage and linear change from baseline in the maximum diameter of the PCED at weeks 4 and 8, as well as the achievement of complete epithelial healing at week 8 maintained at week 10. The study includes a screening period to identify eligible participants, followed by a treatment phase and subsequent follow-up visits to monitor clinical outcomes. The duration of participant involvement is determined by the scheduled assessments through week 10. The study is expected to conclude by September 2028.
Treatment
The investigational product is cenegermin, administered as OXERVATE 20 micrograms/ml eye drops, which is an ophthalmic solution for ocular use. This study evaluates the efficacy of this recombinant human nerve growth factor in participants with persistent corneal epithelial defect.
A placebo consisting of the vehicle for cenegermin drug product will be administered for comparison.
Auxiliary treatments include COLIROFTA, a solution containing oxybuprocaine hydrochloride and tetracaine hydrochloride, administered via ocular use at a dosage of 5 gtt. Additionally, tropicamide will be utilized for auxiliary purposes at a dosage of 2 gtt.
Efficacy
The efficacy of cenegermin ophthalmic solution will be evaluated in participants with persistent corneal epithelial defect (PCED). The primary endpoint is the achievement of complete epithelial healing at week 4 and its maintenance at week 8.
Secondary efficacy endpoints include:
- The percentage change from baseline in the maximum diameter of the PCED at week 4 and week 8.
- The achievement of complete epithelial healing at week 8 and its maintenance at week 10.
- The linear change from baseline in the maximum diameter of the PCED, measured in millimeters, at week 4.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Men or women aged 18 years or above
- Participants with PCED in the study eye with the following characteristics: a. PCED ≥ 1.0 mm in greatest diameter b. PCED of at least 14 days duration, refractory to 1 or more conventional nonsurgical treatments (ocular lubricants, discontinuation of preserved drops and medications, bandage contact lens) showing no clinical resolution.
- Use of most ophthalmic medications (including glaucoma medications) indicated for ocular conditions other than PCED is permitted in the study eye, if the participant has been on a stable dose for at least 30 days and does not expect to have change in dosing regimen throughout the entire duration of the study. Please see exclusion criteria list for exceptions.
- Use of prophylactic antibiotics in the study eye is permitted if the participant is already receiving them prior to enrollment.
- Able to sign the inform consent as described in the protocol, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF).
Exclusion Criteria
- Contralateral eye with vision of no light perception or anatomic absence of contralateral eye.
- Active ocular infection or inflammation in the study eye as follows: a. Bacterial, fungal, or protozoal infection at screening b. Active infectious stromal infiltrates or edema at screening c. Acute anterior uveitis of grade 2 or greater (SUN 2025) within 30 days of screening d. Acute intermediate uveitis or posterior uveitis within 30 days of screening e. Acute inflammation of the sclera or conjunctiva if it is not associated with the PCED
- Corneal epithelial defect associated with stromal thinning greater than 30% (estimated on clinical slit lamp exam) or if associated with stromal infiltrate (corneal haze is acceptable), in the study eye.
- Severe eyelid disease in the study eye, such as: a. Mechanical eyelid abnormalities that have direct contact with the PCED (e.g., trichiasis, severe entropion with lid margin keratinization, etc, if in direct contact with the PCED) b. Lagophthalmos greater than 2 mm as measured in the clinic c. Existing diagnosis of nocturnal lagophthalmos or Parkinson’s disease d. Inability to fully close eyelids despite voluntary eyelid closure e. Severe ectropion with abnormal eyelid-globe congruity (e.g., the lower eyelid does not come into contact with the globe due to severe ectropion)
- Severe end-stage ocular surface disease in the study eye, including but not limited to: a. Severe limbal stem cell deficiency, defined as involvement of more than 270 cumulative degrees or more of limbal stem cell deficiency b. Keratinization of the bulbar conjunctiva or lid margin
- Use of the following medications and devices within the indicated time window prior to randomization: a. Local medications in study eye: − Any prior use of cenegermin − Blood-derived (autologous serum) or other ocular surface re-epithelizing agents, anesthetic use by the participant outside of the clinical exam setting, insulin, or steroids (unless associated with post-operative treatment regimen) within 7 days − Botox (botulinum toxin) injections for pharmacologic tarsorrhaphy within 90 days b. Systemic medications: − High-dose systemic corticosteroids (greater than 0.5 mg/kg/day) within 30 days − Any changes in oral medication regimen intended for the treatment of the ocular surface (eg, oral doxycycline) within 30 days, or planned changes during the study period − Systemic opioid use within 30 days − Use of any systemic investigational product, ocular investigational product in the study eye, radiation of the head or neck, or systemic chemotherapy within 90 days, or planned to occur during the study period c. Devices: − Use of contact lens (including therapeutic contact lens) within 7 days, or planned use of contact lens during the study period, in the study eye − Anticipated need for punctal occlusion in the study eye during the study period. Participants with punctal occlusion or punctal plugs inserted prior to the study are eligible for enrolment provided that the punctual occlusion is maintained throughout the study.
- Presence of acute severe systemic disease as follows: a. Any acute or active severe systemic inflammatory disease (eg, acute systemic Stevens-Johnson Syndrome, acute systemic GVHD, severe systemic Sjogren’s, mucous membrane pemphigoid) b. Presence of any systemic disease that may affect ability to participate in the clinical study according to the clinical judgment of the investigator
- Recent surgery or amniotic membrane therapy as follows: a. Recent major surgical procedure for the treatment of PCED (eg, conjunctival flap, complete tarsorrhaphy, superficial keratectomy for epithelial defect revision, etc) within 14 days of randomization b. Presence of amniotic membrane from AMT for ocular surface indication if not dissolved within area of PCED within 14 days of randomization. Examples include: − Sutured AMT − Self-retaining AMT −Contact lens combined with AMT −Other AMT treatment for the ocular surface c. Partial tarsorrhaphy (temporary or permanent) placed within 14 days of randomization. If a participant is enrolled with partial tarsorrhaphy placed more than 14 days prior to randomization, then the tarsorrhaphy must not be removed for the entire duration of the study.
- Contraception: a. Females of child-bearing age (defined as not surgically sterilized or post-menopausal for at least 1 year) are excluded if they meet any 1 of the following conditions: − Are known to be pregnant − Have a positive urine pregnancy test at baseline visit − Are planning to become pregnant during study period − Are breastfeeding − Are unwilling to use acceptable form of contraception until 30 days after the study treatment period is complete b. Male fertile participants (ie, not surgically sterilized by vasectomy) unwilling to use an acceptable form of contraception (male condom with spermicidal cream or jelly) until 30 days after the study treatment period is complete
- Known active substance abuse or dependency, including but not limited to alcohol, illicit drugs, marijuana, or misuse of prescription medications within 30 days of randomization
- Known or suspected ocular malignancy (e.g., ocular surface, intraocular, ocular adnexa), or presence of cancer or any other systemic disease that may affect the ability to participate in the clinical study in the opinion of the investigator including basal cell carcinoma of the head
- Any ocular or systemic disorder that might hinder the efficacy of the study treatment or its evaluation or could be judged by the investigator to be incompatible with the study visit schedule or conduct
- Concurrent participation in another investigational study
- Hypersensitivity: a. Known or suspected allergy to any components of the cenegermin formulation b. Known hypersensitivity to 1 of the components of the study or procedural medications (eg, fluorescein)
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Czechia | Not Yet Recruiting | 14 May 2026 | 7 |
 France | Not Yet Recruiting | 14 May 2026 | 12 |
 Germany | Not Yet Recruiting | 14 May 2026 | 11 |
 Hungary | Not Yet Recruiting | 14 May 2026 | 7 |
 Italy | Not Yet Recruiting | 14 May 2026 | 17 |
 The Netherlands | Not Yet Recruiting | 14 May 2026 | — |
 Poland | Recruiting | 14 May 2026 | 14 |
 Spain | Recruiting | 14 May 2026 | 16 |
| Netherlands | — | — | 7 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
OXERVATE 20 micrograms/ml eye drops, solution | Test | EYE DROPS, SOLUTION | OCULAR USE | 00 | 16 | PRD10292276 |
Vehicle for cenegermin drug product | Placebo | N/A | — | — | — | N/A |
TROPICAMIDE | Other | — | OCULAR USE | 2 | 40 | SUB11342MIG |
COLIROFTA ANESTÉSICO DOBLE 1 MG/ML + 4 MG/ML COLIRIO EN SOLUCIÓN | Other | COLIRIO EN SOLUCIÓN | OCULAR USE | 5 | 40 | PRD7478890 |