A Study to Evaluate the Performance and Safety of CBL-102 Versus Vismed® Multi Eye Drops in the Management of Dry Eye (RESTA)

The primary objectives of this investigation were to show that the performance of CBL-102 Eye Drops is non-inferior to that of Vismed® Multi eye drops in subjects with moderate to severe keratoconjunctivitis sicca after 28 days, and to assess the safety of CBL-102 Eye Drops during a 90-day period with treatment administered 3 to 6 times per day.

Study Overview

• Status: Completed
• Conditions: Dry Eye
• Intervention / Treatment: Device: CBL-102 eye drops; Device: Vismed Multi eye drops

Detailed Description

This was a multicenter, randomized, parallel group, investigator-masked, non-inferiority study. Approximately 84 subjects were planned to be randomized in a 1:1 ratio.

The primary performance endpoint was the mean change from baseline (CFB) in the study eye at Day 28 in the Ocular surface fluorescein staining score as assessed by the Oxford Scheme.

Following a screening visit (Visit 1) and a 2-week washout with povidone 2% artificial tear (ART), participants were randomized on Day 0 (Visit 2) with follow-up visits on Day 28 ±3 (Visit 4) and Day 90 ±10 (Visit 5). A telephone assessment took place on Day 7 ±1 ('Visit 3') for safety and compliance.

• Study Type: Interventional
• Enrollment (Actual): 92
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Le Kremlin-Bicêtre, France, 94270
    • Hôpital Kremlin-Bicêtre

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age of at least 18 and ability to read, understand, and provide written voluntary informed consent on the Ethics Committee approved Informed Consent Form
2. Ability and willingness to comply with all treatment and follow-up and study procedures
3. Use of tear substitutes for at least 2.5 months prior to inclusion, and agreement to use multidose preservative-free ART (Aqualarm® U.P. povidone 2% eye drops in 10 mL bottles) up to 6 times a day for at least 2 weeks immediately prior to randomization
4. Symptom score ≥ 1 for at least 2 out of the 7 following symptoms (rated 0 to 4): sensation of dryness, foreign body, burning, stinging, itching, blurred vision, sensitivity to light

5. At least 1 eye with the following signs of keratoconjunctivitis sicca :

   • Tear break-up time of 10 sec (mean of 3 measurements) at both screening visit and inclusion visit
   • Total ocular surface staining score ≥ 4 and ≤ 9 at both screening visit and inclusion visit. This assessment combines corneal, nasal and temporal bulbar conjunctival fluorescein staining, each graded 0-5 according to the Oxford Scheme
6. A decimal visual acuity with habitual correction equal to or better than 0.1 (Monoyer chart) in both eyes
7. No systemic treatment or who had received stable systemic treatment (unchanged for 1 month or longer)

8. Female subjects had to be into 1 of the following categories:

   • Post-menopausal
   • Surgically sterile
   • Using birth control method throughout the duration of the study
9. Female of childbearing potential needed a negative urine pregnancy test result at screening

Exclusion Criteria:

1. Severe blepharitis

2. Severe ocular dryness accompanied by 1 of the following:

   • Lid abnormality
   • Corneal disease
   • Ocular surface metaplasia
   • Filamentary keratitis
   • Corneal neovascularization
3. Use of contact lenses at inclusion or within 90 days prior to study start
4. History of ocular surgery, including laser surgery, in either eye within 180 days prior to study start
5. History of ocular trauma, non-dry eye ocular inflammation, or ocular infection within 90 days prior to study start
6. History of ocular allergic disease or ocular herpes within 1 year prior to study start
7. History of any inflammatory ulcerative keratitis, recurrent corneal erosion, or uveitis
8. Known hypersensitivity or contraindications to any of the ingredients in the test or comparator products or ART
9. Initiation of, or changes to, concomitant medication that could affect dry eye within 30 days prior to Visit 1 (Screening) or with planned initiation or changes of such medications during the study
10. Ocular therapy (either eye) with any ophthalmic medication, except tear substitutes, within 2 weeks prior to study start
11. Expected use of ocular therapy during the study
12. Use of topical ocular steroidal or non-steroidal anti-inflammatory medication within 30 days prior to study start
13. Expected use of ocular therapy with immunosuppressants during the study or use of ocular immunosuppressants within 90 days prior to study start
14. Use of occlusion therapy with non-resorbable lacrimal or punctum plugs within 90 days prior to study start or use of resorbable plugs
15. Use or planned use of therapy such as LipiFlow® or BlephEx®
16. Breastfeeding females
17. Participation in any drug or device clinical investigation within 30 days prior to entry into study and/or during the period of study participation

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CBL-102 eye drops; CE marked medical device, tear substitute containing 0.24% hyaluronic acid salt, carbomer and medium chain triglycerides, presented in 10 mL bottles	Device: CBL-102 eye drops; CBL-102 eye drops, 3 to 6 times per day for 3 months
Active Comparator: Vismed Multi eye drops; CE marked medical device, tear substitute containing 0.18% sodium hyaluronate, presented in 10 mL bottles	Device: Vismed Multi eye drops; Vismed Multi eye drops, 3 to 6 times per day for 3 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Ocular Surface Fluorescein Staining Score at Day 28	Mean change from baseline (CFB) in the study eye in Ocular Surface Fluorescein Staining (OSFS) scored according to the Oxford Scheme. The Oxford Scheme is a validated scale consisting of a series of panels labelled A to E in order of increasing severity. Grade 0 corresponds to panel A increasing to Grade 5 corresponding to more than Panel E, with punctate dots representing staining. The 3 regions, cornea, nasal and temporal bulbar conjunctiva are graded separately from 0 (best outcome) to 5 (worst outcome), with the Ocular Surface Fluorescein Score (OSFS) ranging from 0 (best outcome) to 15 (worst outcome). The OSFS is the sum score of the 3 sub-scores (corneal, nasal and temporal regions). The study eye was the eligible eye with the highest OSFS score at baseline, which needed to be ≥4 and ≤9 on the 15-grade Oxford Scheme. If both eyes were eligible and had the same OSFS score, the study eye was the right eye.	Baseline (Day 0), Visit 4 (Day 28)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Ocular Surface Fluorescein Staining Score at Day 90 (Visit 5)	Mean change from baseline (CFB) in the study eye in Ocular Surface Fluorescein Staining (OSFS) scored according to the Oxford Scheme. The Oxford Scheme is a validated scale consisting of a series of panels labelled A to E in order of increasing severity. Grade 0 corresponds to panel A increasing to Grade 5 corresponding to more than Panel E, with punctate dots representing staining. The 3 regions, cornea, nasal and temporal bulbar conjunctiva are graded separately from 0 to 5, with the OSFS score ranging from 0 (best outcome) to 15 (worst outcome). The study eye was the eligible eye with the highest OSFS score at baseline, which needed to be ≥4 and ≤9 on the 15-grade Oxford Scheme. If both eyes were eligible and had the same OSFS score, the study eye was the right eye.	Baseline (Day 0), Visit 5 (Day 90)
Change From Baseline in Corneal Fluorescein Staining Score at Day 28 (Visit 4) and at Day 90 (Visit 5)	Mean change from baseline (CFB) in the study eye in Corneal Fluorescein Staining (OSFS) scored according to the Oxford Scheme. The Oxford Scheme is a validated scale consisting of a series of panels labelled A to E in order of increasing severity. Grade 0 corresponds to panel A increasing to Grade 5 corresponding to more than Panel E, with punctate dots representing staining. The Corneal Region is graded separately from 0 (best outcome) to 5 (worst outcome).	Baseline (Day 0), Visit 4 (Day 28) and Visit 5 (Day 90)
Change From Baseline in Nasal Conjunctival Fluorescein Staining Score at Day 28 (Visit 4) and at Day 90 (Visit 5)	Mean change from baseline (CFB) in the study eye in Nasal Conjunctival Fluorescein Staining scored according to the Oxford Scheme. The Oxford Scheme is a validated scale consisting of a series of panels labelled A to E in order of increasing severity. Grade 0 corresponds to panel A increasing to Grade 5 corresponding to more than Panel E, with punctate dots representing staining. The Nasal conjunctival region is graded separately from 0 (best outcome) to 5 (worst outcome).	Baseline (Day 0), Visit 4 (Day 28) and Visit 5 (Day 90)
Change From Baseline in Temporal Conjunctival Fluorescein Staining Score at Day 28 (Visit 4) and at Day 90 (Visit 5)	Mean change from baseline (CFB) in the study eye in Temporal Conjunctival Fluorescein Staining scored according to the Oxford Scheme. The Oxford Scheme is a validated scale consisting of a series of panels labelled A to E in order of increasing severity. Grade 0 corresponds to panel A increasing to Grade 5 corresponding to more than Panel E, with punctate dots representing staining. The Temporal Conjunctival region is graded separately from 0 (best outcome) to 5 (worst outcome).	Baseline (Day 0), Visit 4 (Day 28), Visit 5 (Day 90)
Change From Baseline in Global Sum Score of Dry Eye Symptoms at Day 28 (Visit 4) and at Day 90 (Visit 5)	The global sum score (scale 0-28) of dry eye symptoms assessed 7 items: sensation of dryness, foreign body, burning, stinging, itching, blurred vision, sensitivity to light, each graded from 0 (absent) to 4 (severe and/or disabling and constant).	Baseline (Day 0), Visit 4 (Day 28) and Visit 5 (Day 90)
Change From Baseline in the Ocular Surface Disease-Quality of Life (OSD-QoL®) at Day 90 (Visit 5)	The OSD-QoL® questionnaire is a validated instrument for measuring dry eye severity and impairment. It includes 28 items divided into 7 dimensions: Daily activities, Difficulties with work and handicap, Giving up makeup, Acknowledgement of the disease, Acceptance of the disease, Fear for the future, and Emotional well-being. A Global Question: "How do you feel when considering your eye problems?" (included in the Fear for the future dimension) is also evaluated separately. The converted score for each dimension ranges from 0 to 100, with a higher score reflecting a better quality of life.	Baseline (Day 0), Visit 5 (Day 90)
Change From Baseline in Tear Film Break Up Time (TFBUT) at Day 28 (Visit 4) and at Day 90 (Visit 5)	The Tear Film Break Up Time (TFBUT) after fluorescein instillation, measured the time between the last blink and the first appearance of a dry spot or disruption of the tear film. The TFBUT was measured in tenth of seconds with a stopwatch provided to the sites. It was conducted 3 times and the means was calculated.	Baseline (Day 0), Visit 4 (Day 28), Visit 5 (Day 90)
Change From Baseline in Schirmer Test at Day 28 (Visit 4)	Tear fluid secretion was assessed by the un-anaesthetized Schirmer test in the study eye with graduated strips in millimeters. Schirmer paper test strips were carefully inserted over the lower eyelid margin. The strips were removed after 5 minutes and the amount of tear fluid secretion ready to the nearest mm from the graduated strip margins.	Baseline (Day 0), Visit 4 (Day 28)
Frequency of Eye Drop Instillation	Mean daily frequency of investigational eye drop instillations as reported in participant's diary	From Day 0 to Day 90, an average of 3 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events questionnaire	Occurrence rates of ocular and non-ocular treatment emergent adverse events (TEAEs)	through study completion, an average of 3 months
Visual acuity measurement	Visual acuity measurement using Monoyer scale	Baseline (Day 0), Visit 4 (Day 28) and Visit 5 (Day 90)

Collaborators and Investigators

• Sponsor: Laboratoire Chauvin
• Collaborators: Bausch & Lomb Incorporated
• Investigators: Principal Investigator: Marc Labetoulle, M.D Ph.D, Hôpital Kremlin-Bicêtre

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2017
• Primary Completion (Actual): June 2, 2020
• Study Completion (Actual): June 2, 2020

Study Registration Dates

• First Submitted: November 28, 2017
• First Submitted That Met QC Criteria: December 8, 2017
• First Posted (Actual): December 11, 2017

Study Record Updates

• Last Update Posted (Actual): May 14, 2025
• Last Update Submitted That Met QC Criteria: April 29, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: dry eye, tear substitute, ocular lubricant
• Additional Relevant MeSH Terms: Eye Diseases; Corneal Diseases; Lacrimal Apparatus Diseases; Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Keratitis; Dry Eye Syndromes; Keratoconjunctivitis Sicca; Pharmaceutical Solutions; Ophthalmic Solutions
• Other Study ID Numbers: CBL-2017-01; 2017-A01099-44 (Other Identifier: ANSM Registry Office RCB - France)

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