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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Neurotrophic Keratitis
• Intervention / Treatment: Biological: CSB-001 Ophthalmic Solution 0.1%; Biological: Vehicle Control

• Study Type: Interventional
• Enrollment (Estimated): 128
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Operations Representative; Phone Number: 919-205-0012; Email: clinicaltrials@clarisbio.com

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1K1
      • Recruiting
      • Dr. Gregory Moloney
      • Contact: Study Coordinator
  • Ontario
    • Ottawa, Ontario, Canada, K1G 5L1
      • Recruiting
      • Precision Cornea Centre
      • Contact: Study Coordinator
    • Toronto, Ontario, Canada, M5T 3A9
      • Recruiting
      • Kensington Eye Institute
      • Contact: Study Coordinator
• United States
  • Arizona
    • Cave Creek, Arizona, United States, 85331
      • Recruiting
      • Eye Care North
      • Contact: Study Coordinator
  • California
    • Loma Linda, California, United States, 92354
      • Recruiting
      • Loma Linda University Eye Institute
      • Contact: Study Coordinator
    • Los Angeles, California, United States, 90095
      • Recruiting
      • UCLA Stein Eye Institute
      • Contact: Study Coordinator
    • Los Angeles, California, United States, 90041
      • Active, not recruiting
      • Global Research Foundation
    • Los Angeles, California, United States, 90013
      • Recruiting
      • Nvision Clinical Research, LLC
      • Contact: Study Coordinator
    • Murrieta, California, United States, 92562
      • Recruiting
      • LoBue Laser and Eye Medical Center, Inc.
      • Contact: Study Coordinator
    • Pasadena, California, United States, 91107
      • Recruiting
      • California Eye Specialists Medical group Inc.
      • Contact: Study Coordinator
    • Rancho Cordova, California, United States, 95670
      • Recruiting
      • Martel Eye Medical Group
      • Contact: Study Coordinator
    • San Diego, California, United States, 92122
      • Recruiting
      • Gordon Schanzlin New Vision Institute
      • Contact: Study Coordinator
    • Torrance, California, United States, 90505
      • Recruiting
      • Atlantis Eyecare
      • Contact: Study Coordinator
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado - Dept. of Ophthalmology
      • Contact: Study Coordinator
    • Colorado Springs, Colorado, United States, 80907
      • Recruiting
      • Vision Institute
      • Contact: Study Coordinator
    • Littleton, Colorado, United States, 80120
      • Recruiting
      • Corneal Consultants of Colorado
      • Contact: Study Coordinator
  • Florida
    • Boynton Beach, Florida, United States, 33437
      • Recruiting
      • Advanced Research
      • Contact: Study Coordinator
    • Jacksonville, Florida, United States, 32256
      • Active, not recruiting
      • Bowden Eye and Associates
    • Ormond Beach, Florida, United States, 32174
      • Recruiting
      • International Eye Associates, PA
      • Contact: Study Coordinator
    • Palm Beach, Florida, United States, 33418
      • Recruiting
      • Bascom Palmer Eye Institute at Palm Beach Gardens
      • Contact: Study Coordinator
    • Tampa, Florida, United States, 33603
      • Recruiting
      • International Research Center
      • Contact: Study Coordinator
  • Georgia
    • Atlanta, Georgia, United States, 30339
      • Recruiting
      • Eye Consultants of Atlanta
      • Contact: Study Coordinator
  • Indiana
    • Carmel, Indiana, United States, 46290
      • Recruiting
      • Midwest Cornea Associates, LLC
      • Contact: Study Coordinator
    • Indianapolis, Indiana, United States, 46260
      • Recruiting
      • Price Vision Group
      • Contact: Study Coordinator
  • Kentucky
    • Edgewood, Kentucky, United States, 41017
      • Recruiting
      • Cincinnati Eye Institute
      • Contact: Study Coordinator
    • Lexington, Kentucky, United States, 40517
      • Active, not recruiting
      • Kentucky Eye Institute
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • Johns Hopkins Hospital
      • Contact: Study Coordinator
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Active, not recruiting
      • Tufts Medical Center
  • Minnesota
    • Edina, Minnesota, United States, 55436
      • Recruiting
      • Cornea and Contact Lens Institute of Minnesota
      • Contact: Study Coordinator
    • Minnetonka, Minnesota, United States, 55305
      • Recruiting
      • Minnesota Eye Consultants
      • Contact: Study Coordinator
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Recruiting
      • Tauber Eye Center
      • Contact: Study Coordinator
    • Saint Louis, Missouri, United States, 63131
      • Recruiting
      • Ophthalmology Associates
      • Contact: Study Coordinator
  • New Jersey
    • Palisades Park, New Jersey, United States, 07650
      • Recruiting
      • Metropolitan Eye Research and Surgery Institute
      • Contact: Study Coordinator
  • New York
    • Babylon, New York, United States, 11702
      • Recruiting
      • SightMD
      • Contact: Study Coordinator
    • Slingerlands, New York, United States, 12159
      • Recruiting
      • Cornea Consultants of Albany
      • Contact: Study Coordinator
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke Eye Center
      • Contact: Study Coordinator
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • Recruiting
      • Eye Consultants of North Dakota
      • Contact: Study Coordinator
  • Ohio
    • Columbus, Ohio, United States, 43212
      • Recruiting
      • The Ohio State University, Department of Ophthalmology and Visual Sciences
      • Contact: Study Coordinator
  • Oregon
    • Portland, Oregon, United States, 97210
      • Recruiting
      • Devers Eye Institute
      • Contact: Study Coordinator
  • Pennsylvania
    • Hazle Township, Pennsylvania, United States, 18202
      • Recruiting
      • Hazleton Eye Specialists
      • Contact: Study Coordinator
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Scheie Eye Institute
      • Contact: Study Coordinator
    • Pittsburgh, Pennsylvania, United States, 15213
      • Active, not recruiting
      • UPMC Eye Center
  • South Carolina
    • Ladson, South Carolina, United States, 29456
      • Recruiting
      • Carolina Cataract & Laser Center
      • Contact: Study Coordinator
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57108
      • Recruiting
      • Vance Thompson Vision
      • Contact: Study Coordinator
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Recruiting
      • BLINK Research Center, LLC
      • Contact: Study Coordinator
  • Texas
    • Austin, Texas, United States, 78712
      • Recruiting
      • University of Texas at Austin; The Mitchel and Shannon Wong Eye Institute
      • Contact: Study Coordinator
    • San Antonio, Texas, United States, 78212
      • Recruiting
      • Stuart A. Terry, MD PA
      • Contact: Study Coordinator
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Recruiting
      • Virginia Eye Consultants
      • Contact: Study Coordinator

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CSB-001 Investigational Treatment Arm; One drop CSB-001 four times daily for 8 weeks in the study eye	Biological: CSB-001 Ophthalmic Solution 0.1%; CSB-001: human recombinant dHGF (5-amino acid deleted hepatocyte growth factor)
Placebo Comparator: Vehicle Control Arm; One drop matching vehicle four times daily for 8 weeks in the study eye	Biological: Vehicle Control; Matching vehicle control without the drug substance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Safety as Assessed by Adverse Event Reporting	Incidence of ocular and systemic adverse events	Screening through Week 10
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
Safety as Assessed by Intraocular Pressure	Change in baseline in intraocular pressure using the Goldmann tonometry	Screening through Week 10
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy as Assessed by Corneal Healing	Time to corneal healing based on assessments by the Central Reading Center	Week 1 through Week 10
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
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
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
Efficacy as Assessed by Time to Corneal Healing	Time to corneal healing based on assessments by the investigator	Week 1 through Week 10
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

Collaborators and Investigators

• Sponsor: Claris Biotherapeutics, Inc.

Publications and helpful links

General Publications

• Hamrah P, Yavuz Saricay L, Ozmen MC. Cutting Edge: Topical Recombinant Nerve Growth Factor for the Treatment of Neurotrophic Keratopathy-Biologicals as a Novel Therapy for Neurotrophic Keratopathy. Cornea. 2022 Jun 1;41(6):673-679. doi: 10.1097/ICO.0000000000002974. Epub 2022 Feb 2.

Study record dates

Study Major Dates

• Study Start (Actual): August 24, 2021
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): July 1, 2024

Study Registration Dates

• First Submitted: May 25, 2021
• First Submitted That Met QC Criteria: May 27, 2021
• First Posted (Actual): June 1, 2021

Study Record Updates

• Last Update Posted (Estimated): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 26, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Corneal Diseases; Keratitis; Pharmaceutical Solutions; Ophthalmic Solutions
• Other Study ID Numbers: CSB-C20-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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