KB801 versus placebo for healing corneal defects in stage 2 or 3 neurotrophic keratitis

A Phase 1/2, Multicenter, Double-Masked, Placebo-Controlled Study of KB801 in Subjects With Stage 2 or 3 Neurotrophic Keratitis

This tests whether KB801 eye drops can safely heal persistent corneal epithelial defects in adults with stage 2 or 3 neurotrophic keratitis.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Krystal Biotech, Inc. (Industry-sponsored)
• Locations: 9 sites (Irvine, California and 8 other locations)
• Trial ID: NCT06999733 on ClinicalTrials.gov

What this trial studies

This is a Phase 1/2, multicenter, double-masked, placebo-controlled trial that randomizes adults with stage 2 or 3 neurotrophic keratitis 1:1 to receive topical KB801 or vehicle once daily for 8 weeks. KB801 is a replication-defective HSV-1–derived vector engineered to deliver full-length human nerve growth factor to the cornea. Participants return for a 2-week post-treatment visit and then safety follow-up visits every 3 months for about one year to monitor safety and durability of corneal healing. The trial focuses on safety, tolerability, and preliminary signs of efficacy in promoting epithelial defect closure.

Who should consider this trial

Good fit: Adults aged 18 or older with stage 2 or 3 neurotrophic keratitis who have a persistent corneal epithelial defect of at least 1 mm that did not improve between screening visits and who can comply with study procedures are ideal candidates.

Not a fit: Patients with active ocular infection or inflammation unrelated to NK, pregnant women, or those whose defects are improving or smaller than 1 mm are unlikely to benefit from enrollment.

Why it matters

Potential benefit: If successful, KB801 could promote durable corneal healing and reduce vision loss or need for surgical interventions in patients with advanced neurotrophic keratitis.

How similar studies have performed: Topical recombinant NGF therapies have shown benefit for neurotrophic keratitis, but using an HSV-1–based gene delivery vector like KB801 is a novel approach with limited prior clinical data.

Eligibility criteria

Inclusion Criteria:

1. The subject must have read, understood, and signed an Institutional Review Board (IRB) approved Informed Consent Form and must be willing and able to comply with study procedures and instructions.
2. Aged ≥ 18 years at the time of informed consent.
3. Diagnosis of Stage 2 or Stage 3 NK, as defined by the Mackie criteria.
4. Persistent corneal epithelial defect (PCED) between Screening 1 and Screening 2 without clinical improvement during that time. PCED is defined as a focal loss of the cornea's outermost cell layer and can include involvement of the deeper stromal layers (i.e., corneal ulcer).
5. PCED at Screening 1 must have a minimum of 1 mm of any linear measurement of defect.
6. A negative pregnancy test at Screening 1 and Day 1 for women of child-bearing potential.

Exclusion Criteria:

1. An active ocular infection (bacterial, viral, fungal or protozoal) or active ocular inflammation not related to NK in the study eye as assessed by Investigator at Screening 1 or 2.
2. Use of any prohibited therapies at Screening or anticipated need for topical treatments other than the investigational product or products allowed per protocol in the study eye from Screening through the study Treatment Period

   a. Sufficient washout of prohibited therapies must occur prior to meeting eligibility criteria.
3. Anticipated use of therapeutic contact lenses or contact lens wear for refractive correction during the study Treatment Period in the study eye.
4. Evidence of corneal ulceration involving the posterior third of the corneal stroma, corneal melting, descemetocele, impending or perforation in the study eye at the time of Screening 1 or 2.
5. PCED at Screening 1 or 2 of \> 8 mm maximum linear measurement in any eye.
6. The central 3 mm of corneas contain PCED bilaterally at Screening 1 or 2.
7. Anticipated need for punctal occlusion of the study eye during the Treatment Period.
8. Presence or history of any ocular or systemic disorder or condition that might hinder the efficacy of the study treatment or its evaluation, could possibly interfere with the interpretation of study results, or could be judged by the Investigator to be incompatible with the study visit schedule or conduct (e.g., progressive or degenerative corneal or retinal conditions, uveitis, optic neuritis, poorly controlled diabetes, autoimmune disease, systemic infection, neoplastic diseases).
9. Participation in another clinical study or treatment with an investigational agent 30 days or 5 half-lives, whichever is longer, prior to Day 1 (participation in a non-interventional observational study is permitted).
10. Intraocular surgery on the eligible eye(s) within 6 months prior to Screening 1, and any ophthalmic condition that may require surgery on the study eye during the Treatment Period. An exception to the preceding statement is allowed if, in the opinion of the Investigator, the ocular surgery is deemed the cause of the NK.
11. Corneal transplantation (i.e., keratoplasty) of the study eye within the past 2 years or a history of multiple keratoplasty operations to the study eye regardless of timing. This includes full- or partial-thickness, or endothelial keratoplasty.
12. Subject who is pregnant or nursing.
13. Subject who is unwilling to comply with contraception requirements per-protocol (for subjects of childbearing potential).
14. Subject who is known to be noncompliant or is unlikely to comply with the requirements of the study protocol, in the opinion of the Investigator.

Where this trial is running

Irvine, California and 8 other locations

• UC Irvine Alpha Clinic — Irvine, California, United States (Not_yet_recruiting)
• Azul Vision - California Eye Specialists Medical Group Inc. — Pasadena, California, United States (Recruiting)
• Midwest Cornea Associates — Carmel, Indiana, United States (Recruiting)
• Vance Thompson Vision — Alexandria, Minnesota, United States (Recruiting)
• Minnesota Eye Consultants — Minnetonka, Minnesota, United States (Recruiting)
• St. Louis Eye Institute — Town and Country, Missouri, United States (Recruiting)
• Metropolitan Eye Research and Surgery Institute — Palisades Park, New Jersey, United States (Recruiting)
• Vance Thompson Vision — West Fargo, North Dakota, United States (Recruiting)
• UPMC Vision Institute — Pittsburgh, Pennsylvania, United States (Not_yet_recruiting)

Study contacts

• Study coordinator: David Sweet, MD, PhD

Conditions Neurotrophic Keratitis; Persistent Corneal Epithelial Defect; Corneal Epithelial Defect