Study to Evaluate the Safety and Efficacy of CSB-001 Ophthalmic Solution 0.1% in Neurotrophic Keratitis Subjects

Neurotrophic Keratitis Clinical Trial

Official title:

A Multi-Center, Randomized, Double-Masked, Vehicle-Controlled, Parallel-Group, Study to Evaluate the Safety and Efficacy of CSB-001 Ophthalmic Solution 0.1% in Stage 2 and 3 Neurotrophic Keratitis Subjects

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04909450
• Other study ID #: CSB-C20-003
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: August 24, 2021
• Est. completion date: July 2024

Study information

• Verified date: February 2024
• Source: Claris Biotherapeutics, Inc.
• Contact: Clinical Operations Representative
• Phone: 919-205-0012
• Email: clinicaltrials[@]clarisbio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will enroll subjects with stage 2 or 3 neurotrophic keratitis. Subjects will be randomized in a 1:1 ratio to the CSB-001 investigational treatment arm or vehicle control arm. All subjects will dose with the randomized treatment four times daily for 8 weeks (controlled treatment phase). During the controlled treatment phase, subjects will return to the clinic weekly from Day 0 to Week 8, and again at Week 10. Subjects randomized to the vehicle arm who are not healed will have the opportunity to participate in an open-label uncontrolled treatment phase.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 128
• Est. completion date: July 2024
• Est. primary completion date: April 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Subjects with stage 2 (PED) or stage 3 (corneal ulcer) neurotrophic keratitis (NK). Subjects with bilateral NK may enroll in the study but only one eye will be selected as the study eye (worse eye) and be treated with test article.
• Subjects with no clinical evidence of improvement in the PED or corneal ulcer within the 2 weeks prior to study enrollment despite the use of conventional non-surgical treatments for neurotrophic keratitis (e.g., preservative-free artificial tears, gels or ointments; discontinuation of preserved topical drops and medications that can decrease corneal sensitivity; therapeutic contact lenses [either silicone hydrogel or rigid gas permeable]) as determined by the investigator or referring physician's medical record.
• Subjects with clinical evidence of decreased corneal sensitivity within the area of the PED or corneal ulcer and outside of the area of the defect in at least one corneal quadrant in the study eye in the opinion of the investigator assessed with a cotton wisp.
• Pinhole distance visual acuity score = 75 ETDRS letters measured with a LogMAR chart (= 0.2 LogMAR, = 20/32 Snellen or worse Snellen or = 0.625 decimal fraction) in the study eye.
• Subjects must have the ability and willingness to comply with study procedures.

Exclusion Criteria:

• Any active ocular infection (bacterial, viral, fungal, or protozoal) or active ocular inflammation not related to NK in either eye in the opinion of the investigator. Infectious epithelial keratitis including herpetic keratitis (i.e., dendritic lesions or geographic ulcers) in either eye is excluded. Subjects on oral antibiotic at the time of screening are eligible but should continue the medication for the duration of the study.
• Previous use of Oxervate in the study eye with last administration within the past 2 months.
• Any other ocular disease, except glaucoma, that will require topical ocular treatment in the study eye over the course of the study.
• Use of any other topical treatments other than the study medication provided by the Sponsor and allowed by the study protocol can be administered to the study eye over the course of the study. The following are exceptions: a) Allowance for use of preservative-free antibiotic eye drops if prescribed by the investigator and b) Allowance for use of a non-preserved IOP-lowering prostaglandin topical ocular drop administered once-daily (QD) in glaucomatous eyes over the course of the study. Note: Other inclusion/exclusion criteria apply.

Related Conditions & MeSH terms

• Keratitis
• Neurotrophic Keratitis

Intervention

Biological:
• CSB-001 Ophthalmic Solution 0.1%
CSB-001: human recombinant dHGF (5-amino acid deleted hepatocyte growth factor)
• Vehicle Control
Matching vehicle control without the drug substance

Locations

Country	Name	City	State
Canada	Precision Cornea Centre	Ottawa	Ontario
Canada	Kensington Eye Institute	Toronto	Ontario
Canada	Dr. Gregory Moloney	Vancouver	British Columbia
United States	Eye Consultants of Atlanta	Atlanta	Georgia
United States	University of Colorado - Dept. of Ophthalmology	Aurora	Colorado
United States	University of Texas at Austin; The Mitchel and Shannon Wong Eye Institute	Austin	Texas
United States	SightMD	Babylon	New York
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	Tufts Medical Center	Boston	Massachusetts
United States	Advanced Research	Boynton Beach	Florida
United States	Midwest Cornea Associates, LLC	Carmel	Indiana
United States	Eye Care North	Cave Creek	Arizona
United States	Vision Institute	Colorado Springs	Colorado
United States	The Ohio State University, Department of Ophthalmology and Visual Sciences	Columbus	Ohio
United States	Duke Eye Center	Durham	North Carolina
United States	Cincinnati Eye Institute	Edgewood	Kentucky
United States	Cornea and Contact Lens Institute of Minnesota	Edina	Minnesota
United States	Eye Consultants of North Dakota	Fargo	North Dakota
United States	Hazleton Eye Specialists	Hazle Township	Pennsylvania
United States	Price Vision Group	Indianapolis	Indiana
United States	Bowden Eye and Associates	Jacksonville	Florida
United States	Tauber Eye Center	Kansas City	Missouri
United States	Carolina Cataract & Laser Center	Ladson	South Carolina
United States	Kentucky Eye Institute	Lexington	Kentucky
United States	Corneal Consultants of Colorado	Littleton	Colorado
United States	Loma Linda University Eye Institute	Loma Linda	California
United States	Global Research Foundation	Los Angeles	California
United States	Nvision Clinical Research, LLC	Los Angeles	California
United States	UCLA Stein Eye Institute	Los Angeles	California
United States	BLINK Research Center, LLC	Memphis	Tennessee
United States	Minnesota Eye Consultants	Minnetonka	Minnesota
United States	LoBue Laser and Eye Medical Center, Inc.	Murrieta	California
United States	Virginia Eye Consultants	Norfolk	Virginia
United States	International Eye Associates, PA	Ormond Beach	Florida
United States	Metropolitan Eye Research and Surgery Institute	Palisades Park	New Jersey
United States	Bascom Palmer Eye Institute at Palm Beach Gardens	Palm Beach	Florida
United States	California Eye Specialists Medical Group Inc.	Pasadena	California
United States	Scheie Eye Institute	Philadelphia	Pennsylvania
United States	UPMC Eye Center	Pittsburgh	Pennsylvania
United States	Devers Eye Institute	Portland	Oregon
United States	Martel Eye Medical Group	Rancho Cordova	California
United States	Ophthalmology Associates	Saint Louis	Missouri
United States	Stuart A. Terry, MD PA	San Antonio	Texas
United States	Gordon Schanzlin New Vision Institute	San Diego	California
United States	Vance Thompson Vision	Sioux Falls	South Dakota
United States	Cornea Consultants of Albany	Slingerlands	New York
United States	International Research Center	Tampa	Florida
United States	Atlantis Eyecare	Torrance	California

Sponsors (1)

Lead Sponsor	Collaborator
Claris Biotherapeutics, Inc.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy as Assessed by Complete Corneal Healing	Proportion of subjects achieving complete corneal healing as assessed by the Central Reading Center	Week 8 through Week 10
Primary	Safety as Assessed by Adverse Event Reporting	Incidence of ocular and systemic adverse events	Screening through Week 10
Primary	Safety as Assessed by Slit-lamp Biomicroscopy	Change from baseline in staining using NEI scale (0 = absent to 3 = severe for 5 areas of the cornea) with Grade 0 (no staining) to maximum of Grade 15	Screening through Week 10
Primary	Safety as Assessed by Intraocular Pressure	Change in baseline in intraocular pressure using the Goldmann tonometry	Screening through Week 10
Primary	Safety as Assessed by Dilated Fundus Examination	Change from baseline in observed anomalies of the peripheral retina, macula, choroid, optic nerve and vitreous (cup/disc ratio)	Screening through Week 10
Primary	Safety as Assessed by Best-Corrected Distance Visual Acuity	Change from baseline using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart	Screening through Week 10
Secondary	Efficacy as Assessed by Corneal Healing	Time to corneal healing based on assessments by the Central Reading Center	Week 1 through Week 10
Secondary	Efficacy as Assessed by Corneal Healing at Week 4	Proportion of subjects achieving corneal healing at Week 4 assessed by the Central Reading Center	Week 1 through Week 4
Secondary	Efficacy as Assessed by Corneal Healing at Week 4 and Week 8 Sustained for Two Weeks	Proportion of subjects achieving corneal healing at Week 4 and Week sustained for 2 weeks as assessed by the investigator	Weeks 4 and 8 through Week 10
Secondary	Efficacy as Assessed by Decrease in Lesion Size	Time to =20% decrease in lesion size (maximum diameter) from baseline assessed by the Central Reading Center	Week 1 through Week 10
Secondary	Efficacy as Assessed by Time to Corneal Healing	Time to corneal healing based on assessments by the investigator	Week 1 through Week 10
Secondary	Efficacy as Assessed by Best Corrected Distance Visual Acuity	Proportion of subjects achieving a =15-letter gain in the study eye from baseline in Best Corrected Distance Visual Acuity	Week 1 through Weeks 4 and 8