Open-label Trial to Evaluate Efficacy and Safety of rhNGF on Corneal Thickness Via AS-OCT in Neurotrophic Keratitis

NCT06411145 | Withdrawn Phase 4 FDA Drug

• 1 other identifier: NGF0223
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Primary Objective: To assess the efficacy of cenegermin-bkbj (20 mcg/mL) ophthalmic solution on overall corneal thickness via AS-OCT in patients with stage 3 neurotrophic keratitis with respect to change from baseline at weeks 4, 8, and 16. Secondary Objectives: To assess the effects of cenegermin-bkbj (20 mcg/mL) ophthalmic solution on corneal stromal thickness via AS-OCT in patients with stage 3 neurotrophic keratitis with respect to change from baseline at weeks 4, 8, and 16. To assess the effects of cenegermin-bkbj (20 mcg/mL) ophthalmic solution on corneal stromal reflectivity via AS-OCT in patients with stage 3 neurotrophic keratitis with respect to change from baseline at weeks 4, 8, and 16. To assess the effects of cenegermin-bkbj (20 mcg/mL) ophthalmic solution on corneal sensitivity via Cochet-Bonnet aesthesiometer in the center of the lesion with respect to change from baseline at weeks 4, 8, and 16.

Conditions

Neurotrophic Keratitis; Neurotrophic Keratopathy; Corneal Ulcer

Keywords

stage 3 keratitis; cenegermin-bkbj; OXERVATE®; rhNGF

Outcome Measures

Primary Outcomes (1)

• Change in overall corneal thickness via AS-OCT from baseline to weeks 4, 8, and 16.

  The changes from baseline in corneal thickness via AS-OCT from baseline to weeks 4, 8, and 16 will be analyzed by means of an adjusted longitudinal regression model

  weeks 4, 8, and 16.

Secondary Outcomes (4)

• Change in corneal stromal thickness via AS-OCT from baseline to weeks 4, 8, and 16.

  weeks 4, 8, and 16

• Change in stromal reflectivity via AS-OCT from baseline to weeks 4, 8, and 16

  weeks 4, 8, and 16

• Change in corneal sensitivity within lesion area via Cochet-Bonnet from baseline to weeks 4, 8, and 16.

  weeks 4, 8, and 16

• Frequency and severity of TEAE throughout the study until the FU week 16 assessment (Day 112 +/- 3)

  Throughout the study until Day 112 +/- 3

Study Arms (1)

Cenegermin-bkbj

EXPERIMENTAL

cenegermin-bkbj (20 mcg/mL) ophthalmic solution on corneal thickness administered as topical drops via anterior segment optical coherence tomography (AS-OCT), where cenergermin-bkbj stands for Topical Recombinant Human Nerve Growth Factor (rhNGF). Cenegermin-bkbj, the active ingredient of OXERVATE® 0.002% (20 mcg/mL) cenegermin-bkbj ophthalmic solution, is structurally identical to the human nerve growth factor (NGF) protein made in ocular tissues.

Drug: OXERVATE® 0.002%

Interventions

OXERVATE® 0.002% DRUG

Cenegermin-bkbj (20 mcg/mL) is an ophthalmic solution contained in a multiple-dose vial. The topical drops are administered 6 times/day for a 8-week course.

Also known as: cenegermin-bkbj

Cenegermin-bkbj

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must be ≥18 years of age at time of screening.
• Patient must be stage 3 NK in the study eye defined by the Mackie Criteria at baseline (Appendix 4).
• Evidence of decreased corneal sensitivity in the study eye as measured by Cochet-Bonnet esthesiometry (≤4 cm in the center of the neurotrophic lesion) at baseline.
• Patients who have only one functional eye can be included if they meet all the criteria above and per the Investigator's discretion are proper candidates to designate the one functional eye as the study eye.
• Self-retaining amniotic membrane or any other amniotic topical product may be used prior to baseline visit (Visit 2) but should be removed or fully dissolved by the baseline measurements.
• Patients must have the ability and willingness to comply with study procedures and study product dosing as described in the protocol.
• Only patients who satisfy all informed consent requirements may be included in the study. The patient and/or his/her legal representative must read, sign, and date the Institutional Review Board (IRB)-approved informed consent document before any study-related procedures are performed.

You may not qualify if:

• In the opinion of the Investigator, evidence or confirmed culture of an active ocular infection (bacterial, fungal, protozoal) in either eye at the time of screening or baseline.
• Evidence of a necrotizing herpetic ulcer in either eye at the time of screening or baseline.
• Active or severe corneal/ocular inflammation that requires continuous medical therapy throughout the duration of the treatment, including eyelid-based disorders such as severe MGD or blepharitis.
• Patients with posterior one-third corneal involvement or if posterior one-third of cornea becomes involved during the time between screening and baseline measurements, or at the Investigator's discretion is close to perforation.
• Patients who have excessive, pre-existing corneal opacification.
• Any of the following within 90 days of study enrollment:
• Treatment with Botox (botulinum toxin) injections in the study eye to induce pharmacologic blepharoptosis
• Treatment with intravenous chemotherapy for oncologic pathology
• Patients who have punctal occlusion planned within the study period. Patients who have undergone punctal occlusion prior to entry into the study are eligible for enrollment provided that the punctal occlusion is maintained during the study period. If a punctal plug falls out of the study eye during the study, it must be reinserted within 7 days of discovery via examination by the Investigator.
• Anticipated need to use therapeutic contact lenses, contact lens wear for refractive correction, or scleral contact lenses during the treatment period in the study eye.
• Patients with eyelid or neuromuscular abnormality that may alter eyelid function or closure, thereby increasing exposure; this includes but is not limited to blepharospasm, cranial nerve palsy or paresis, entropion, ectropion, or floppy eyelid syndrome.
• Previously been treated with OXERVATE®
• Ocular surgeries (including but not limited to LASIK, PRK, tube shunt/trabeculectomy, cataract surgery) within the last 6 months.
• History of corneal stromal surgery, including anterior lamellar keratoplasty (ALK), deep anterior lamellar keratoplasty (DALK), and penetrating keratoplasty (PKP) within 12 months of screening visit
• Female patients who are pregnant or lactating at study screening or baseline, or those who are planning pregnancy during the period of study.

Sponsors & Collaborators

• Dompé Farmaceutici S.p.A: lead

MeSH Terms

Conditions

Corneal Ulcer; Keratitis

Interventions

cenegermin

Condition Hierarchy (Ancestors)

Eye Infections; Infections; Corneal Diseases; Eye Diseases

Study Officials

• Brad Kligman, MD

  SightMD, New York, New York

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Masking Details: This is an open label study, hence masking is not applicable
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Cenegermin-bkbj (20 mcg/mL) ophthalmic solution contained in a multiple-dose vial. The topical drops are administered 6 times/day for a 6-week course.

Study Record Dates

• First Submitted: May 8, 2024
• First Posted: May 13, 2024
• Study Start: April 26, 2024
• Primary Completion: November 12, 2024
• Study Completion: November 12, 2024
• Last Updated: December 2, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share