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

NCT04909450 | Completed Phase 1 FDA Drug

• 1 other identifier: CSB-C20-003
• Study Type: interventional
• Target: 131
• Locations: 2 countries
• Sites: 48

Brief 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.

Conditions

Neurotrophic Keratitis

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (6)

• Efficacy as Assessed by Corneal Healing

  Week 1 through Week 10

• Efficacy as Assessed by Corneal Healing at Week 4

  Week 1 through Week 4

• Efficacy as Assessed by Corneal Healing at Week 4 and Week 8 Sustained for Two Weeks

  Weeks 4 and 8 through Week 10

• Efficacy as Assessed by Decrease in Lesion Size

  Week 1 through Week 10

• Efficacy as Assessed by Time to Corneal Healing

  Week 1 through Week 10

Study Arms (2)

CSB-001 Investigational Treatment Arm

EXPERIMENTAL

One drop CSB-001 four times daily for 8 weeks in the study eye

Biological: CSB-001 Ophthalmic Solution 0.1%

Vehicle Control Arm

PLACEBO COMPARATOR

One drop matching vehicle four times daily for 8 weeks in the study eye

Biological: Vehicle Control

Interventions

CSB-001 Ophthalmic Solution 0.1% BIOLOGICAL

CSB-001: human recombinant dHGF (5-amino acid deleted hepatocyte growth factor)

CSB-001 Investigational Treatment Arm

Vehicle Control BIOLOGICAL

Matching vehicle control without the drug substance

Vehicle Control Arm

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Claris Biotherapeutics, Inc.: lead

Study Sites (48)

Eye Care North

Cave Creek, Arizona, 85331, United States

Location

Loma Linda University Eye Institute

Loma Linda, California, 92354, United States

Location

Nvision Clinical Research, LLC

Los Angeles, California, 90013, United States

Location

Global Research Foundation

Los Angeles, California, 90041, United States

Location

UCLA Stein Eye Institute

Los Angeles, California, 90095, United States

Location

LoBue Laser and Eye Medical Center, Inc.

Murrieta, California, 92562, United States

Location

California Eye Specialists Medical Group Inc.

Pasadena, California, 91107, United States

Location

Martel Eye Medical Group

Rancho Cordova, California, 95670, United States

Location

Gordon Schanzlin New Vision Institute

San Diego, California, 92122, United States

Location

Atlantis Eyecare

Torrance, California, 90505, United States

Location

University of Colorado - Dept. of Ophthalmology

Aurora, Colorado, 80045, United States

Location

Vision Institute

Colorado Springs, Colorado, 80907, United States

Location

Corneal Consultants of Colorado

Littleton, Colorado, 80120, United States

Location

Advanced Research

Boynton Beach, Florida, 33437, United States

Location

Bowden Eye and Associates

Jacksonville, Florida, 32256, United States

Location

International Eye Associates, PA

Ormond Beach, Florida, 32174, United States

Location

Bascom Palmer Eye Institute at Palm Beach Gardens

Palm Beach, Florida, 33418, United States

Location

International Research Center

Tampa, Florida, 33603, United States

Location

Eye Consultants of Atlanta

Atlanta, Georgia, 30339, United States

Location

Midwest Cornea Associates, LLC

Carmel, Indiana, 46290, United States

Location

Price Vision Group

Indianapolis, Indiana, 46260, United States

Location

Cincinnati Eye Institute

Edgewood, Kentucky, 41017, United States

Location

Kentucky Eye Institute

Lexington, Kentucky, 40517, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Cornea and Contact Lens Institute of Minnesota

Edina, Minnesota, 55436, United States

Location

Minnesota Eye Consultants

Minnetonka, Minnesota, 55305, United States

Location

Tauber Eye Center

Kansas City, Missouri, 64111, United States

Location

Ophthalmology Associates

St Louis, Missouri, 63131, United States

Location

Metropolitan Eye Research and Surgery Institute

Palisades Park, New Jersey, 07650, United States

Location

SightMD

Babylon, New York, 11702, United States

Location

Cornea Consultants of Albany

Slingerlands, New York, 12159, United States

Location

Duke Eye Center

Durham, North Carolina, 27710, United States

Location

Eye Consultants of North Dakota

Fargo, North Dakota, 58104, United States

Location

The Ohio State University, Department of Ophthalmology and Visual Sciences

Columbus, Ohio, 43212, United States

Location

Devers Eye Institute

Portland, Oregon, 97210, United States

Location

Hazleton Eye Specialists

Hazle Township, Pennsylvania, 18202, United States

Location

Scheie Eye Institute

Philadelphia, Pennsylvania, 19104, United States

Location

UPMC Eye Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Carolina Cataract & Laser Center

Ladson, South Carolina, 29456, United States

Location

Vance Thompson Vision

Sioux Falls, South Dakota, 57108, United States

Location

BLINK Research Center, LLC

Memphis, Tennessee, 38119, United States

Location

University of Texas at Austin; The Mitchel and Shannon Wong Eye Institute

Austin, Texas, 78712, United States

Location

Stuart A. Terry, MD PA

San Antonio, Texas, 78212, United States

Location

Virginia Eye Consultants

Norfolk, Virginia, 23502, United States

Location

Dr. Gregory Moloney

Vancouver, British Columbia, V5Z 1K1, Canada

Location

Precision Cornea Centre

Ottawa, Ontario, K1G 5L1, Canada

Location

Kensington Eye Institute

Toronto, Ontario, M5T 3A9, Canada

Location

Related Publications (1)

• 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.

  PMID: 35266655 DERIVED

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 25, 2021
• First Posted: June 1, 2021
• Study Start: August 24, 2021
• Primary Completion: May 7, 2024
• Study Completion: June 4, 2024
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (45); CA (3)