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

Sponsor

Claris Biotherapeutics, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04909450

Collaborator

(none)

108

Enrollment

Locations

Arms

17.3

Anticipated Duration (Months)

3.9

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Neurotrophic Keratitis	Biological: CSB-001 Ophthalmic Solution 0.1% Biological: Vehicle Control	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

108 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Aug 24, 2021

Anticipated Primary Completion Date :

Nov 1, 2022

Anticipated Study Completion Date :

Feb 1, 2023

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Efficacy as Assessed by Complete Corneal Healing [Week 8 through Week 10]
Proportion of subjects achieving complete corneal healing as assessed by the Central Reading Center
Safety as Assessed by Adverse Event Reporting [Screening through Week 10]
Incidence of ocular and systemic adverse events
Safety as Assessed by Slit-lamp Biomicroscopy [Screening through Week 10]
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
Safety as Assessed by Intraocular Pressure [Screening through Week 10]
Change in baseline in intraocular pressure using the Goldmann tonometry
Safety as Assessed by Dilated Fundus Examination [Screening through Week 10]
Change from baseline in observed anomalies of the peripheral retina, macula, choroid, optic nerve and vitreous (cup/disc ratio)
Safety as Assessed by Best-Corrected Distance Visual Acuity [Screening through Week 10]
Change from baseline using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart

Secondary Outcome Measures

Efficacy as Assessed by Corneal Healing [Week 1 through Week 10]
Time to corneal healing based on assessments by the Central Reading Center
Efficacy as Assessed by Corneal Healing at Week 4 [Week 1 through Week 4]
Proportion of subjects achieving corneal healing at Week 4 assessed by the Central Reading Center
Efficacy as Assessed by Corneal Healing at Week 4 and Week 8 Sustained for Two Weeks [Weeks 4 and 8 through Week 10]
Proportion of subjects achieving corneal healing at Week 4 and Week sustained for 2 weeks as assessed by the investigator
Efficacy as Assessed by Decrease in Lesion Size [Week 1 through Week 10]
Time to ≥20% decrease in lesion size (maximum diameter) from baseline assessed by the Central Reading Center
Efficacy as Assessed by Time to Corneal Healing [Week 1 through Week 10]
Time to corneal healing based on assessments by the investigator
Efficacy as Assessed by Best Corrected Distance Visual Acuity [Week 1 through Weeks 4 and 8]
Proportion of subjects achieving a ≥15-letter gain in the study eye from baseline in Best Corrected Distance Visual Acuity

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Loma Linda University Eye Institute	Loma Linda	California	United States	92354
2	Global Research Foundation	Los Angeles	California	United States	90041
3	UCLA Stein Eye Institute	Los Angeles	California	United States	90095
4	Martel Eye Medical Group	Rancho Cordova	California	United States	95670
5	Gordon Schanzlin New Vision Institute	San Diego	California	United States	92122
6	Vision Institute	Colorado Springs	Colorado	United States	80907
7	Corneal Consultants of Colorado	Littleton	Colorado	United States	80120
8	Bowden Eye and Associates	Jacksonville	Florida	United States	32256
9	International Eye Associates, PA	Ormond Beach	Florida	United States	32174
10	International Research Center	Tampa	Florida	United States	33603
11	Eye Consultants of Atlanta	Atlanta	Georgia	United States	30339
12	Midwest Cornea Associates, LLC	Carmel	Indiana	United States	46290
13	Price Vision Group	Indianapolis	Indiana	United States	46260
14	Cincinnati Eye Institute	Edgewood	Kentucky	United States	41017
15	Kentucky Eye Institute	Lexington	Kentucky	United States	40517
16	Minnesota Eye Consultants	Minnetonka	Minnesota	United States	55305
17	Tauber Eye Center	Kansas City	Missouri	United States	64111
18	Ophthalmology Associates	Saint Louis	Missouri	United States	63131
19	Metropolitan Eye Research and Surgery Institute	Palisades Park	New Jersey	United States	07650
20	Cornea Consultants of Albany	Slingerlands	New York	United States	12159
21	Devers Eye Institute	Portland	Oregon	United States	97210
22	Scheie Eye Institute	Philadelphia	Pennsylvania	United States	19104
23	UPMC Eye Center	Pittsburgh	Pennsylvania	United States	15213
24	Carolina Cataract & Laser Center	Ladson	South Carolina	United States	29456
25	Vance Thompson Vision	Sioux Falls	South Dakota	United States	57108
26	University of Texas at Austin; The Mitchel and Shannon Wong Eye Institute	Austin	Texas	United States	78712
27	Stuart A. Terry, MD PA	San Antonio	Texas	United States	78212
28	Virginia Eye Consultants	Norfolk	Virginia	United States	23502

Sponsors and Collaborators

Claris Biotherapeutics, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Claris Biotherapeutics, Inc.

ClinicalTrials.gov Identifier:

NCT04909450

Other Study ID Numbers:

CSB-C20-003

First Posted:

Jun 1, 2021

Last Update Posted:

Aug 25, 2022

Last Verified:

Aug 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Keratitis

Ophthalmic Solutions

Study Results

No Results Posted as of Aug 25, 2022