Neurotrophic KeratitisPhase 4DEFENDONCT04485546

Study to Evaluate OXERVATE® in Patients With Stage 1 Neurotrophic Keratitis

A Phase 4 study testing cenegermin-bkbj in people with Neurotrophic Keratitis, run by Dompé Farmaceutici S.p.A at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This study is to evaluate the safety and efficacy of OXERVATE® 0.002% (20 mcg/mL) cenegermin-bkbj ophthalmic solution in patients with Stage 1 neurotrophic keratitis (NK). Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Neurotrophic Keratitis
What is being tested?: cenegermin-bkbj
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 37 participants
Where: 5 sitesUnited States
Study dates: 9 Sep 2020to 30 Mar 2022
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male or female aged ≥ 18 years.
Patients with Stage 1 NK defined by the Mackie criteria

Who cannot join

Evidence of an active ocular infection (bacterial, viral, protozoal) in either eye.
Have current or history of conditions that may confound the study data including but not limited to Ocular Cicatricial Pemphigoid (OCP), Graft Versus Host Disease (GVHD), neuromyelitis optica, uncontrolled dry eye, and Steven Johnson's syndrome.
History of severe systemic allergy or severe ocular allergy (including seasonal conjunctivitis expected during the subject's participation in the trial) or chronic conjunctivitis and/or keratitis other than dry eye disease.
Patients with severe vision loss with no potential for visual improvement in the study eye, in the opinion of the investigator, or if the subject is deemed legally blind.
Ocular surgery or elective ocular surgery expected during participation in the trial.
Patients with eyelid abnormality that may alter eyelid function including but not limited to Blepharospasm, Cerebrovascular accident, entropion, ectropion, floppy lid syndrome.

Trial locations and contacts

5 sites in 1 country.

City, postcode or hospital

5 sites in 1 country

United States5 sites

Boston
Boston, Massachusetts, 02111
Edgewood
Edgewood, Kentucky, 41017
Philadelphia
Philadelphia, Pennsylvania, 19104
San Diego
San Diego, California, 92122
Saint Louis
St Louis, Missouri, 63131

Other trials in United States

About this study

Official title: An 8-week, Multicenter, Open Label, Prospective Study With 24 Weeks of Follow-up to Evaluate Safety and Efficacy of OXERVATE® 0.002% (20 mcg/mL) Cenegermin-bkbj Ophthalmic Solution in Patients With Stage 1 Neurotrophic Keratitis (NK)

This study is to evaluate the safety and efficacy of OXERVATE® 0.002% (20 mcg/mL) cenegermin-bkbj ophthalmic solution in patients with Stage 1 neurotrophic keratitis (NK).

Read the detailed description

This is a 8-week, multicenter, open label, prospective study with 24 weeks of follow-up to evaluate safety and efficacy of OXERVATE® 0.002% (20 mcg/mL) cenegermin-bkbj ophthalmic solution in patients with Stage 1 neurotrophic keratitis (NK)

Conditions: Neurotrophic Keratitis
Being tested: cenegermin-bkbj
Keywords: Stage 1 Neurotrophic Keratitis, Corneal Disease, Ocular Disease
Medical subject headings: Corneal Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

cenegermin-bkbjDrug
Also called OXERVATE® 0.002% (20 mcg/mL) cenegermin-bkbj ophthalmic solution
OXERVATE® 0.002% (20 mcg/mL) cenegermin-bkbj ophthalmic solution administered as one drop in the affected eye(s), 6 times a day at 2-hour intervals for 8 weeks, in patients with Stage 1 neurotrophic keratitis.

Study groups in NCT04485546
Study group	Role	What they receive
OXERVATE® 0.002% (20 mcg/mL) cenegermin-bkbj	Experimental	cenegermin-bkbj ophtalmic solution administered as one drop in affected eye(s) every 2 hours 6 times daily for 8 weeks Receives: Drug: cenegermin-bkbj

What is being measured

The primary outcome is the main question the study is designed to answer.

Corneal Epithelial Healing
Percentage of patients who experienced corneal epithelial healing. Corneal epithelial healing was defined by the central reading center as the absence of persistent epithelial staining abnormalities related to disease.
Measured: Week 8

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

9 Sep 202030 Mar 2022

First posted24 Jul 2020
Study start9 Sep 2020
Primary completion30 Sep 2021
Study completion30 Mar 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Neurotrophic KeratitisStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 37 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04485546
Sponsor's protocol ID: NGF0120
Acronym: DEFENDO
Status last verified: Nov 2025
First submitted: 21 Jul 2020
Last updated: 17 Nov 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Mastropasqua L, Massaro-Giordano G, Nubile M, Sacchetti M. Understanding the Pathogenesis of Neurotrophic Keratitis: The Role of Corneal Nerves. J Cell Physiol. 2017 Apr;232(4):717-724. doi: 10.1002/jcp.25623. Epub 2016 Oct 17.
PubMed 27683068
Hamrah P, Massaro-Giordano M, Schanzlin D, Holland E, Berdy G, Goisis G, Pasedis G, Mantelli F. Phase IV Multicenter, Prospective, Open-Label Clinical Trial of Cenegermin (rhNGF) for Stage 1 Neurotrophic Keratopathy (DEFENDO). Ophthalmol Ther. 2024 Feb;13(2):553-570. doi: 10.1007/s40123-023-00866-y. Epub 2024 Jan 4.
PubMed 38175466

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 1/2
A Phase 1/2, Single-Dose, Multicenter, Dose Escalation, Clinical Trial to Evaluate the Safety and Efficacy of MR-146: An Open-Label Part 1 in Participants With Stage 1 or 2 Neurotrophic Keratopathy and a Double-Masked Part 2 in Participants With Stage 2 Neurotrophic Keratopathy
Neurotrophic Keratopathy
RecruitingPhase 2
Efficacy of Topical Mesenchymal Stromal Cell Secretome for Ocular Surface Disease
Persistent Corneal Epithelial Defect, Corneal Epithelial Disorders
RecruitingPhase 3
An Efficacy and Safety Study of Cenegermin Ophthalmic Solution Compared With Vehicle in the Treatment of PCED
Persistent Corneal Epithelial Defect
RecruitingPhase 2
A Multicenter, Randomized, Vehicle-Controlled, Double-Masked to Open-Label Study to Evaluate the Safety and Efficacy of Lacripep in Subjects With Neurotrophic Keratitis
Neurotrophic Keratitis
RecruitingPhase 4
Effect of Acoltremon Ophthalmic Solution 0.003% on Signs and Symptoms of Ocular Surface Disease in Stage I Neurotrophic Keratopathy Patients With Tear Deficiency
Ocular Surface Disease, Neurotrophic Keratopathy Stage 1

All Neurotrophic Keratitis trials

Study at a glance

From the registry record, last updated by the sponsor on 17 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An 8-week, Multicenter, Open Label, Prospective Study With 24 Weeks of Follow-up to Evaluate Safety and Efficacy of OXERVATE® 0.002% (20 mcg/mL) Cenegermin-bkbj Ophthalmic Solution in Patients With Stage 1 Neurotrophic Keratitis (NK)
ClinicalTrials.gov ID: NCT04485546
Acronym / sponsor ID: DEFENDO / NGF0120
Conditions: Neurotrophic Keratitis
Keywords: Stage 1 Neurotrophic Keratitis, Corneal Disease, Ocular Disease
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 37 participants (actual)
Lead sponsor: Dompé Farmaceutici S.p.AIndustry (pharma, biotech, devices)
Collaborators: Dompé, US, Inc.
Study start: 9 Sep 2020 (actual)
Primary completion: 30 Sep 2021 (actual)
Study completion: 30 Mar 2022 (actual)
First posted: 24 Jul 2020 (actual)
Results: Posted 23 Jun 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This study is to evaluate the safety and efficacy of OXERVATE® 0.002% (20 mcg/mL) cenegermin-bkbj ophthalmic solution in patients with Stage 1 neurotrophic keratitis (NK).

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
OXERVATE® 0.002% (20 mcg/mL) cenegermin-bkbj	Experimental	Drug: cenegermin-bkbjcenegermin-bkbj ophtalmic solution administered as one drop in affected eye(s) every 2 hours 6 times daily for 8 weeks

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

Male or female aged ≥ 18 years.
Patients with Stage 1 NK defined by the Mackie criteria

Key exclusion criteria (6 listed)

Evidence of an active ocular infection (bacterial, viral, protozoal) in either eye.
Have current or history of conditions that may confound the study data including but not limited to Ocular Cicatricial Pemphigoid (OCP), Graft Versus Host Disease (GVHD), neuromyelitis optica, uncontrolled dry eye, and Steven Johnson's syndrome.
History of severe systemic allergy or severe ocular allergy (including seasonal conjunctivitis expected during the subject's participation in the trial) or chronic conjunctivitis and/or keratitis other than dry eye disease.
Patients with severe vision loss with no potential for visual improvement in the study eye, in the opinion of the investigator, or if the subject is deemed legally blind.
Ocular surgery or elective ocular surgery expected during participation in the trial.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
cenegermin-bkbjAlso: OXERVATE® 0.002% (20 mcg/mL) cenegermin-bkbj ophthalmic solutionOXERVATE® 0.002% (20 mcg/mL) cenegermin-bkbj ophthalmic solution administered as one drop in the affected eye(s), 6 times a day at 2-hour intervals for 8 weeks, in patients with Stage 1 neurotrophic keratitis.	Drug	OXERVATE® 0.002% (20 mcg/mL) cenegermin-bkbj

Primary outcome

Corneal Epithelial Healing
Time frame: Week 8
Percentage of patients who experienced corneal epithelial healing. Corneal epithelial healing was defined by the central reading center as the absence of persistent epithelial staining abnormalities related to disease.

Results and safety

Results posted to the registry on 23 Jun 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
OXERVATE® 0.002% (20 mcg/mL) Cenegermin-bkbj	37	29

Primary outcome: Corneal Epithelial Healing

Time frame: Week 8. Count of participants. Unit: Participants

Measure	OXERVATE® 0.002% (20 mcg/mL) Cenegermin-bkbj n = 33
No	5
Yes	28

Population analysed: Full Analysis Set (FAS) - All enrolled patients who received at least one dose of the study drug. The FAS was used both for efficacy and safety analyses. Observed cases (n=33)

Adverse events

Time frame: 34 Weeks. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
OXERVATE® 0.002% (20 mcg/mL) Cenegermin-bkbj - Study Eye	1 of 37 (2.7%)	22 of 37 (59.5%)	0 of 37
OXERVATE® 0.002% (20 mcg/mL) Cenegermin-bkbj - Non Study Eye	0 of 37 (0%)	13 of 37 (35.1%)	0 of 37
OXERVATE® 0.002% (20 mcg/mL) Cenegermin-bkbj - Systemic	7 of 37 (18.9%)	16 of 37 (43.2%)	1 of 37

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 Nov 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 27683068Mastropasqua L, Massaro-Giordano G, Nubile M, Sacchetti M. Understanding the Pathogenesis of Neurotrophic Keratitis: The Role of Corneal Nerves. J Cell Physiol. 2017 Apr;232(4):717-724. doi: 10.1002/jcp.25623. Epub 2016 Oct 17.
Derived from this study: PubMed 38175466Hamrah P, Massaro-Giordano M, Schanzlin D, Holland E, Berdy G, Goisis G, Pasedis G, Mantelli F. Phase IV Multicenter, Prospective, Open-Label Clinical Trial of Cenegermin (rhNGF) for Stage 1 Neurotrophic Keratopathy (DEFENDO). Ophthalmol Ther. 2024 Feb;13(2):553-570. doi: 10.1007/s40123-023-00866-y. Epub 2024 Jan 4.
Individual participant dataSharing planned: No

Related trials for Neurotrophic Keratitis

RecruitingPhase 1/2
A Phase 1/2, Single-Dose, Multicenter, Dose Escalation, Clinical Trial to Evaluate the Safety and Efficacy of MR-146: An Open-Label Part 1 in Participants With Stage 1 or 2 Neurotrophic Keratopathy and a Double-Masked Part 2 in Participants With Stage 2 Neurotrophic Keratopathy
Neurotrophic Keratopathy
RecruitingPhase 2
Efficacy of Topical Mesenchymal Stromal Cell Secretome for Ocular Surface Disease
Persistent Corneal Epithelial Defect, Corneal Epithelial Disorders
RecruitingPhase 3
An Efficacy and Safety Study of Cenegermin Ophthalmic Solution Compared With Vehicle in the Treatment of PCED
Persistent Corneal Epithelial Defect
RecruitingPhase 2
A Multicenter, Randomized, Vehicle-Controlled, Double-Masked to Open-Label Study to Evaluate the Safety and Efficacy of Lacripep in Subjects With Neurotrophic Keratitis
Neurotrophic Keratitis
RecruitingPhase 4
Effect of Acoltremon Ophthalmic Solution 0.003% on Signs and Symptoms of Ocular Surface Disease in Stage I Neurotrophic Keratopathy Patients With Tear Deficiency
Ocular Surface Disease, Neurotrophic Keratopathy Stage 1

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Flavio Mantelli, MD, PhD study chair

Domp Farmaceutici SpA

5 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing cenegermin-bkbj in people with Neurotrophic Keratitis, run by Dompé Farmaceutici S.p.A at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Jun 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Corneal Epithelial Healing (time frame: Week 8). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04485546, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Nov 2025.