Clinical trial NCT04909450: Study to Evaluate the Safety and Efficacy of CSB-001 Ophthalmic Solution 0.1% in Neurotrophic Keratitis Subjects
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Neurotrophic Keratitis
Lead sponsor: Claris Biotherapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2021-06-01
Enrollment: 131
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Efficacy as Assessed by Complete Corneal Healing
timeFrame: Week 8 through Week 10
measure: Safety as Assessed by Adverse Event Reporting
timeFrame: Screening through Week 10
measure: Safety as Assessed by Slit-lamp Biomicroscopy
timeFrame: Screening through Week 10
measure: Safety as Assessed by Intraocular Pressure
timeFrame: Screening through Week 10
measure: Safety as Assessed by Dilated Fundus Examination
timeFrame: Screening through Week 10
measure: Safety as Assessed by Best-Corrected Distance Visual Acuity
timeFrame: Screening through Week 10
Secondary outcomes:
measure: Efficacy as Assessed by Corneal Healing
timeFrame: Week 1 through Week 10
measure: Efficacy as Assessed by Corneal Healing at Week 4
timeFrame: Week 1 through Week 4
measure: Efficacy as Assessed by Corneal Healing at Week 4 and Week 8 Sustained for Two Weeks
timeFrame: Weeks 4 and 8 through Week 10
measure: Efficacy as Assessed by Decrease in Lesion Size
timeFrame: Week 1 through Week 10
measure: Efficacy as Assessed by Time to Corneal Healing
timeFrame: Week 1 through Week 10
measure: Efficacy as Assessed by Best Corrected Distance Visual Acuity
timeFrame: Week 1 through Weeks 4 and 8
Other outcomes:
Locations:
city: Cave Creek
country: United States
facility: Eye Care North
state: Arizona
city: Loma Linda
country: United States
facility: Loma Linda University Eye Institute
state: California
city: Los Angeles
country: United States
facility: Nvision Clinical Research, LLC
state: California
city: Los Angeles
country: United States
facility: Global Research Foundation
state: California
city: Los Angeles
country: United States
facility: UCLA Stein Eye Institute
state: California
city: Murrieta
country: United States
facility: LoBue Laser and Eye Medical Center, Inc.
state: California
city: Pasadena
country: United States
facility: California Eye Specialists Medical Group Inc.
state: California
city: Rancho Cordova
country: United States
facility: Martel Eye Medical Group
state: California
city: San Diego
country: United States
facility: Gordon Schanzlin New Vision Institute
state: California
city: Torrance
country: United States
facility: Atlantis Eyecare
state: California
city: Aurora
country: United States
facility: University of Colorado - Dept. of Ophthalmology
state: Colorado
city: Colorado Springs
country: United States
facility: Vision Institute
state: Colorado
city: Littleton
country: United States
facility: Corneal Consultants of Colorado
state: Colorado
city: Boynton Beach
country: United States
facility: Advanced Research
state: Florida
city: Jacksonville
country: United States
facility: Bowden Eye and Associates
state: Florida
city: Ormond Beach
country: United States
facility: International Eye Associates, PA
state: Florida
city: Palm Beach
country: United States
facility: Bascom Palmer Eye Institute at Palm Beach Gardens
state: Florida
city: Tampa
country: United States
facility: International Research Center
state: Florida
city: Atlanta
country: United States
facility: Eye Consultants of Atlanta
state: Georgia
city: Carmel
country: United States
facility: Midwest Cornea Associates, LLC
state: Indiana
city: Indianapolis
country: United States
facility: Price Vision Group
state: Indiana
city: Edgewood
country: United States
facility: Cincinnati Eye Institute
state: Kentucky
city: Lexington
country: United States
facility: Kentucky Eye Institute
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Edina
country: United States
facility: Cornea and Contact Lens Institute of Minnesota
state: Minnesota
city: Minnetonka
country: United States
facility: Minnesota Eye Consultants
state: Minnesota
city: Kansas City
country: United States
facility: Tauber Eye Center
state: Missouri
city: Saint Louis
country: United States
facility: Ophthalmology Associates
state: Missouri
city: Palisades Park
country: United States
facility: Metropolitan Eye Research and Surgery Institute
state: New Jersey
city: Babylon
country: United States
facility: SightMD
state: New York
city: Slingerlands
country: United States
facility: Cornea Consultants of Albany
state: New York
city: Durham
country: United States
facility: Duke Eye Center
state: North Carolina
city: Fargo
country: United States
facility: Eye Consultants of North Dakota
state: North Dakota
city: Columbus
country: United States
facility: The Ohio State University, Department of Ophthalmology and Visual Sciences
state: Ohio
city: Portland
country: United States
facility: Devers Eye Institute
state: Oregon
city: Hazle Township
country: United States
facility: Hazleton Eye Specialists
state: Pennsylvania
city: Philadelphia
country: United States
facility: Scheie Eye Institute
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Eye Center
state: Pennsylvania
city: Ladson
country: United States
facility: Carolina Cataract & Laser Center
state: South Carolina
city: Sioux Falls
country: United States
facility: Vance Thompson Vision
state: South Dakota
city: Memphis
country: United States
facility: BLINK Research Center, LLC
state: Tennessee
city: Austin
country: United States
facility: University of Texas at Austin; The Mitchel and Shannon Wong Eye Institute
state: Texas
city: San Antonio
country: United States
facility: Stuart A. Terry, MD PA
state: Texas
city: Norfolk
country: United States
facility: Virginia Eye Consultants
state: Virginia
city: Vancouver
country: Canada
facility: Dr. Gregory Moloney
state: British Columbia
city: Ottawa
country: Canada
facility: Precision Cornea Centre
state: Ontario
city: Toronto
country: Canada
facility: Kensington Eye Institute
state: Ontario
Study officials:
References:
citation: 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.