DEFENDO Long Term Follow-up Study in Stage 1 NK Patients (DEFENDO)

A Long-term Extension Study to Evaluate the Safety and Efficacy of OXERVATE® 0.002% (20 mcg/mL) Cenegermin-bkbj Ophthalmic Solution in Patients With Stage 1 Neurotrophic Keratitis Who Enrolled in the DEFENDO Study (NGF0120)

Primary Objective

To evaluate the long-term safety and efficacy (healing) of OXERVATE® 0.002% (20 mcg/mL) cenegermin-bkbj ophthalmic solution in Stage 1 neurotrophic keratitis (NK) patients who enrolled in the DEFENDO study.

Secondary Objective

To evaluate the long-term efficacy of OXERVATE® 0.002% (20 mcg/mL) cenergemin-bkbj ophthalmic solution in terms of corneal sensitivity, Schirmer I test, tear film break-up time (TFBUT), best corrected distance visual acuity (BCDVA), and quality of life at 24 and 30 months post-treatment

Study Overview

• Status: Completed
• Conditions: Neurotrophic Keratitis
• Intervention / Treatment: Drug: Cenegemin in the DEFENDO Study

Detailed Description

NGF0122 (DEFENDO Long-Term Follow-up) study was a Phase 4, multicenter, open label, long-term follow-up study evaluating safety and efficacy in the patients with Stage 1 Neurotrophic Keratitis (NK) who were enrolled in the NGF0120 (original DEFENDO) study and were treated with OXERVATE® 0.002% (20 mcg/mL) cenegermin-bkbj ophthalmic solution for up to 8 weeks in the NGF0120.

After completing enrollment in the NGF0120 Study, patients were invited to enter the NGF0122 Study (all standard of care permitted) in which two additional long-term follow-up visits occurred at 24- and 30-months post-treatment to evaluate long-term clinical outcomes.

In the NGF0122, study patients enrolled in the NFG0120 study were evaluated starting from week 8, which corresponds to the end of treatment of the NGF0120 study and is to be considered as the baseline of the NGF0122 study itself.

Patients were treated per standard of care including additional OXERVATE® 0.002% if deemed appropriate by the Investigator.

• Study Type: Observational
• Enrollment (Actual): 24

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92037
      • New Vision Institute
  • Kentucky
    • Edgewood, Kentucky, United States, 41017
      • Cincinnati Eye Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02011
      • Tufts Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Scheie Eye Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Stage 1 NK

Description

Inclusion Criteria:

1. Previously enrolled in the DEFENDO Study.
2. Satisfied all Informed Consent requirements. The patient and/or their legal representative read, signed, and dated the IRB approved Informed Consent document before any study-related procedures were performed.
3. Had the ability and willingness to comply with study procedures.

Exclusion Criteria:

Were participating in another study that involved treating the study eye. Participation in non-ocular studies was acceptable provided that the treatment was not considered to be confounding with the DEFENDO Long-Term Follow-up Study, in the opinion of the Investigator.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Group Long-term follow-up; All eligible patients, after completing enrollment in the original DEFENDO Study, were invited to enter the DEFENDO Long-Term Follow-Up Study (all standard of care permitted), according to inclusion and exclusion criteria.

Drug: Cenegemin in the DEFENDO Study; Cenegemin as administered in the original DEFENDO Study. Long-term safety and efficacy of OXERVATE® 0.002% (20 mcg/mL) cenegermin-bkbj ophthalmic solution administered in Stage 1 Neurotrophic Keratitis (NK) patients enrolled in the original DEFENDO Study (NGF0120 / NCT04485546). No intervention was performed in this follow-up / extension study.; Other Names: OXERVATE®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number/Percentage of Patients Who Achieved Corneal Epithelial Healing at NGF0120 Week 8 (EoT NGF0120=Baseline NGF0122) and Remained Healed at Month 24 and Month 30 of the NGF0122 Study	Corneal epithelial at Month 24 and Month 30 of the NGF0122 study was summarized as a binary goal attainment variable (Yes/No) based on the subset of patients who achieved corneal epithelial healing at Week 8 of the NGF0120, as determined by the Central Reading Center (CRC). Healing was defined as the absence of persistent epithelial staining abnormalities related to disease. The persistence (or worsening) of a staining pattern in the same corneal area was considered a failure in terms of healing.	At Month 24 and Month 30 of the NGF0122 study
Number/Percentage of Patients Who Did Not Achieve Corneal Epithelial Healing at NGF0120 Week 8 (EoT NGF0120=Baseline NGF0122) Who Had a Healed Corneal Epithelium at Month 24 and 30 of the NGF0122 Study.	Corneal epithelial healing at the overall Follow-up Month 24 and Month 30 was summarized as a binary goal attainment variable (Yes/No) based on the subset of patients who did not achieve corneal epithelial healing at Week 8 of the NGF0120, as determined by the Central Reading Center (CRC). Healing was defined as the absence of persistent epithelial staining abnormalities related to disease. Epithelial healing took into consideration the Baseline epithelial staining patterns of each patient and their evolution over time.The persistence (or worsening) of a staining pattern in the same corneal area was considered a failure in terms of healing.	At Month 24 and Month 30 of the NGF0122 study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number/Percentage of Patients With an Improvement in Corneal Sensitivity at NGF0120 Week 8 (EoT NGF0120=Baseline NGF0122) Who Still Had Improvement in Corneal Sensitivity at Month 24 and 30 of the NGF0122 Study.	Improvement in corneal sensitivity at the overall Follow-up Month 24 and 30 was assessed as a binary goal attainment variable (Yes/No), based on the subset of patients who achieved an improvement in corneal sensitivity at Week 8 of the NGF0120. Improvement was defined as a change from Baseline > 0 cm in the study eye. Corneal sensitivity was measured in the central National Eye Institute (NEI) zone using the Cochet-Bonnet aesthesiometer, before the instillation of any dilating or anesthetic drops. The filament was extended to its full length (6 cm), then retracted in 0.5 cm increments until the patient reported feeling contact. The filament length at which sensation was reported was recorded. Higher values indicate better sensitivity. Please note that patients without a Yes/No response available (=missing data) are not considered in the analysis. More in details, these missing patients are 4 at month 24 and 3 at month 30.	At Month 24 and Month 30 of the NGF0122 study
Number/Percentage of Patients Who Did Not Improved Corneal Sensitivity at NGF0120 Week 8 (EoT NGF0120=Baseline NGF0122) and Improved Corneal Sensitivity at Month 24 and 30 of the NGF0122 Study.	Improvement in corneal sensitivity at the overall Follow-up Month 24 and 30 was assessed as a binary goal attainment variable (Yes/No), based on the subset of patients who did not achieve an improvement in corneal sensitivity at Week 8 of the NGF0120. Improvement was defined as a change from Baseline > 0 cm in the study eye. Corneal sensitivity was measured using the Cochet-Bonnet aesthesiometer in the central NEI zone before the instillation of any anesthetic or dilating drops. The filament was extended to 6 cm and retracted in 0.5 cm increments until the patient reported sensation upon contact. Higher values indicate better sensitivity. Please note that patients without a Yes/No response available (=missing data) are not considered in the analysis. More in details, these missing patients are 1 at month 30 only.	At Month 24 and Month 30 of the NGF0122 study
Mean Change in Corneal Sensitivity From NGF0120 Baseline and NGF0120 Week 8 (EoT NGF0120=Baseline NGF0122) to Month 24 and Month 30 of the NGF0122 Study.	Corneal sensitivity at the overall Follow-up Month 24 and Month 30 measured (in cm) in the qualifying NEI (National Eye Institute) zone of the study eye using the Cochet-Bonnet aesthesiometer before the instillation of any anesthetic or dilating drops. Improvement was defined as a change from Baseline > 0 cm in the study eye. Higher values indicate better sensitivity.	At Month 24 and Month 30 of the NGF0122 study
Change From NGF0120 Baseline and NGF0120 Week 8 (EoT NGF0120=Baseline NGF0122) in Schirmer I Scores to Month 24 and Month 30 of the NGF0122 Study.	Change in Schirmer I test scores was assessed as a continuous outcome in the study eye from Baseline and at Week 8 of the NGF0120 to Month 24 and Month 30. The Schirmer I test was conducted on unanesthetized eyes using standardized paper test strips placed in the lower temporal lid margin of each eye. After 5 minutes, the strip was removed, and the length of the moistened area (in millimeters) was recorded.This test measures aqueous tear production. Any change in mean score >0 was considered an improvement in dry eye. Higher scores indicate better tear production, while lower values are associated with more severe dry eye. A positive change from Baseline was interpreted as improvement.	At Month 24 and Month 30 of the NGF0122 study
Change From NGF0120 Baseline and NGF0120 Week 8 (EoT NGF0120=Baseline NGF0122) in TFBUT to Months 24 and 30 of the NGF0122.	Change in Tear Film Break-Up Time was evaluated in the study eye. TFBUT was measured in seconds using fluorescein dye under cobalt blue illumination. After fluorescein instillation, the patient blinked once or twice, then kept the eye open; the time to first dry spot was recorded. Two values were averaged, or three if differing by >2 seconds. TFBUT values ranged from 0 seconds (tear film instability) to ≥10 seconds (normal stability). Values <5 seconds suggest clinically relevant tear film dysfunction. A positive change from Baseline or Week 8 (>0 seconds) was interpreted as improvement in tear film stability.	At Month 24 and Month 30 of the NGF0122 study
Number/Percentage of Patients Who Achieved a 15-letter Improvement in BCDVA From NGF0120 Baseline and NGF0120 Week 8 (EoT NGF0120=Baseline NGF0122) to Month 24 and Month 30 of the NGF0122 Study.	Best Corrected Distance Visual Acuity (BCDVA) at the overall Follow-up Month 24 and Month 30 was assessed in the study eye using the ETDRS visual acuity chart at a distance of 4 meters (13.1 feet), prior to any administration of anesthetic or mydriatic eye drops. Results were recorded as the number of letters correctly identified on the chart. This outcome evaluated the number and percentage of patients who gained at least 15 letters in BCDVA from DEFENDO Baseline and week 8, at Month 24 and Month 30. A gain of ≥15 letters is considered a clinically meaningful improvement corresponding to approximately three lines on the ETDRS chart. The endpoint was analyzed as a binary variable (Yes/No).	At Month 24 and Month 30 of the NGF0122 study
Change From NGF0120 Baseline and NGF0120 Week 8 (EoT NGF0120=Baseline NGF0122) to Month 24 and Month 30 of the NGF0122 Study.	Best Corrected Distance Visual Acuity (BCDVA) at Month 24 and Month 30 was assessed in the study eye using the ETDRS visual acuity chart at 4 meters (13.1 feet), before any anesthetic or mydriatic eye drops or ocular procedures. Scores were recorded in logMAR units, ranging from -0.3 (better visual acuity) to 1.0 (poorer acuity). Higher logMAR values indicate worse vision. A negative change in logMAR (i.e., <0) indicated an improvement in visual acuity. Mean values and standard deviations were summarized descriptively at each timepoint.	At Month 24 and Month 30 of the NGF0122 study
Change From NGF0120 Baseline and NGF0120 Week 8 (EoT NGF0120 = Baseline NGF0122) in Quality of Life (QoL) Expressed by the IDEEL to Months 24 and 30 of the NGF0122 Study.	"Impact of Dry Eye on Everyday Life" (IDEEL) is a 57-item questionnaire assessing dry eye impact (and consequently QoL), composed by 6 domains: Daily Activities; Higher score = less impact; Emotional Impact: Higher score = less impact on emotions; Impact on Work: Higher score = less impact on work; Symptom Bother: Higher score = greater symptom bother; Treatment Bother: Higher score = less treatment-related bother; Treatment Effectiveness: Higher score = greater satisfaction with treatment effectiveness For 5 of 6 domains (Symptom Bother), higher scores on a 0-100 scale indicated improved quality of life relative to dry eye symptoms. For the domain of "symptom bother", a higher score indicated greater symptom bother. For this reason no total score, but only subscores, is calculated.	At Month 24 and Month 30 of the NGF0122 study
Change From NGF0120 Baseline and NGF0120 Week 8 (EoT NGF0120=Baseline NGF0122) in Quality of Life Measured With EuroQol 5-Dimension 5-Level (EQ-5D-5L) to Months 24 and 30 of the NGF0122 Study.	The EQ-5D-5L is a standardized questionnaire what measures the health status in 5 areas-mobility, self-care, usual activities, pain/discomfort, and anxiety/depression-with a rating scale of 1 (no problems) to 5 (extreme problems), where higher scores indicated worse problems. The questionnaire also asks the patient to rate their current health ("how good or bad your health is today") on a scale from 0 (worst health you can imagine) to 100 (best health you can imagine). On a 0-100 scale, a higher "your health today" score indicated better health. The EQ-5D-5L questionnaire was self-administered by the patient before any ophthalmic procedures at either visit. Please note that the severity level reported corresponds to the maximum experienced by the patient (for example, if a patient has one mild AE and one moderate AE, they are counted in the moderate category).	At Month 24 and Month 30 of the NGF0122 study
Number/Percentage of Subjects Reporting Adverse Events (AEs)	An AE was defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product that did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the medicinal (investigational) product, whether or not related to the study product. AEs by severity (categorized as mild, moderate and severe) and relatedness (categorized as related and not related ) are considered - per each single subject - just once, at the greater severity and closest relationship to treatment. Considering that no study IMP was administered and that all standard of care were permitted, AEs must be read as related to any standard of care administered during the FU study.	From NGF0120 Week 8=NGF0122 Baseline to Month 30 of the NGF0122 study
Frequency of Normal and Clinically Significant Abnormal Findings for Slit-lamp Examination Parameters in the Study Eye at Baseline and Week 8 of the NGF0120 and at Month 24 and 30 of the NGF0122	Slit-lamp biomicroscopy was performed in the study eye at Baseline and Week 8 of the NGF0120 study, and at Month 24 and 30. The anterior segment was evaluated under magnification using standard slit-lamp illumination. Parameters included eyelid edema and erythema, lashes, conjunctiva edema and bulbar erythema, cornea edema, endothelial and epithelial changes, lens, sclera, iris, and anterior chamber cells and flare. Findings were assessed visually as normal, abnormal not clinically significant, or abnormal clinically significant, based on clinical judgment and standard ophthalmologic criteria. Only the participants reporting normal and abnormal clinically significant results are shown (along with the percentage vs the "Number Analyzed", for each timepoint) The number of participants with abnormal not clinically significant results can be derived as difference between the sum of the said two categories and the "Number Analyzed", per each parameter and timepoint	Baseline and week 8 of the NGF0120, month 24 and 30 of the NGF0122

Collaborators and Investigators

• Sponsor: Dompé Farmaceutici S.p.A
• Investigators: Study Chair: Flavio Mantelli, MD, PhD, Dompé

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2023
• Primary Completion (Actual): April 12, 2024
• Study Completion (Actual): April 12, 2024

Study Registration Dates

• First Submitted: September 16, 2022
• First Submitted That Met QC Criteria: September 20, 2022
• First Posted (Actual): September 23, 2022

Study Record Updates

• Last Update Posted (Actual): November 28, 2025
• Last Update Submitted That Met QC Criteria: November 18, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Stage 1 NK; Cenegermin; NK; DEFENDO; OXERVATE®; NGF0120 (original DEFENDO study); NGF0122 (DEFENDO long-term follow-up study)
• Additional Relevant MeSH Terms: Eye Diseases; Corneal Diseases; Keratitis; cenegermin
• Other Study ID Numbers: NGF0122

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No