A Phase 2 Study of RCI001 Ophthalmic Solution in Participants With Dry Eye Disease

Official title

A Phase 2, Multi-center, Randomized, Double-Masked and Placebo-Controlled Study Evaluating the Efficacy and Safety of RCI001 Ophthalmic Solution Compared to Placebo in Subjects With Dry Eye

Overview

This is a Phase 2 clinical study designed to evaluate the safety and efficacy of 0.25% RCI001 Ophthalmic Solution compared with placebo in participants with dry eye disease. The study will enroll adults with dry eye disease. After a 2-week run-in period with placebo ophthalmic solution, eligible participants will be randomly assigned to receive either 0.25% RCI001 Ophthalmic Solution or placebo ophthalmic solution in both eyes for 4 weeks. Study treatment will be administered either twice daily or four times daily, depending on the assigned dosing regimen. The main purpose of the study is to determine whether RCI001 improves the signs and symptoms of dry eye disease compared with placebo. The primary assessments include total corneal fluorescein staining and ocular discomfort at Day 28. Safety will be assessed through eye examinations, visual acuity, intraocular pressure, drop comfort, and adverse event monitoring.

Detailed description

This is a multi-center, randomized, double-masked, placebo-controlled Phase 2 study evaluating 0.25% RCI001 Ophthalmic Solution in participants with dry eye disease.

The study will include approximately 6 weeks of participation for each participant, consisting of a 2-week run-in period followed by a 4-week treatment period. Approximately 400 participants are expected to be screened, and approximately 200 eligible participants will be randomized, with approximately 50 participants assigned to each treatment group.

During the run-in period, participants who qualify at screening will receive placebo ophthalmic solution in both eyes according to either a twice-daily or four-times-daily dosing regimen. At the end of the run-in period, eligible participants will be randomized to continue the same dosing frequency and receive either 0.25% RCI001 Ophthalmic Solution or placebo ophthalmic solution bilaterally for 4 weeks.

The four treatment groups are:

0.25% RCI001 Ophthalmic Solution twice daily; placebo ophthalmic solution twice daily; 0.25% RCI001 Ophthalmic Solution four times daily; and placebo ophthalmic solution four times daily.

The study will include four scheduled visits: screening at Day -14, baseline/randomization at Day 1, follow-up at Day 14, and end-of-treatment/study exit at Day 28. Controlled Adverse Environment (CAE) assessments will be used as part of the study procedures.

The primary efficacy endpoints are total corneal fluorescein staining and ocular discomfort assessed before CAE exposure at Day 28. Secondary efficacy assessments include additional ocular staining measures, conjunctival redness, Schirmer's test, tear film break-up time, Ocular Surface Disease Index, ocular discomfort scores, visual analog scale symptoms, and daily symptom diary data.

Safety assessments include visual acuity, slit-lamp biomicroscopy, drop comfort, adverse event monitoring, intraocular pressure, and dilated fundoscopy. The study is designed to compare RCI001 with the corresponding placebo dosing regimen and to evaluate the optimal dosing frequency of RCI001 in the treatment of the signs and symptoms of dry eye disease.

Interventions

• Drug RCI001 Ophthalmic Solution
  RCI001 Ophthalmic Solution is a topical ophthalmic investigational drug containing 0.25% RCI001. Participants assigned to RCI001 treatment will receive one drop in each eye either twice daily (BID) or four times daily (QID), depending on the assigned treatment arm, for 4 weeks.
• Drug Placebo Ophthalmic Solution
  Placebo Ophthalmic Solution is a topical ophthalmic vehicle solution that has the same formulation as RCI001 Ophthalmic Solution but does not contain the active ingredient, RCI001. Participants assigned to placebo treatment will receive one drop in each eye either twice daily (BID) or four times daily (QID), depending on the assigned treatment arm, for 4 weeks.

Primary outcome measures

• Change From Baseline in Total Corneal Fluorescein Staining Score at Day 28 [Time frame: Baseline to Day 28 (Week 4)]
• Change From Baseline in Ocular Discomfort Score at Day 28 [Time frame: Baseline to Day 28 (Week 4)]

Secondary outcome measures (10)

• Change From Baseline in Fluorescein Staining Scores by Region [Time frame: Baseline to Day 14 and Day 28]
• Change From Baseline in Conjunctival Lissamine Green Staining Scores by Region [Time frame: Baseline to Day 14 and Day 28]
• Change From Baseline in Conjunctival Redness Score [Time frame: Baseline to Day 14 and Day 28]
• Change From Baseline in Schirmer's Test Score [Time frame: Baseline to Day 14 and Day 28]
• Change From Baseline in Tear Film Break-Up Time [Time frame: Baseline to Day 14 and Day 28]
• Change From Baseline in Ocular Surface Disease Index Score [Time frame: Baseline to Day 14 and Day 28]
• Change From Baseline in Ocular Discomfort Scale Score [Time frame: Baseline to Day 14 and Day 28]
• Change From Baseline in Visual Analog Scale Symptom Scores [Time frame: Baseline to Day 14 and Day 28]
• Change From Baseline in Ocular Discomfort and 4-Symptom Questionnaire Score [Time frame: Baseline to Day 14 and Day 28]
• Change From Baseline in Daily Symptom Diary Scores [Time frame: Baseline to Day 28]

Eligibility criteria

Inclusion criteria

• At least 18 years of age at the Screening Visit (Visit 1), of either gender and any race.
• Able and willing to provide written informed consent.
• Willing and able to comply with all study procedures.
• Patient-reported history of dry eye for at least 6 months prior to Visit 1.
• History of use or desire to use eye drops for dry eye symptoms within 6 months of Visit 1.
• Best corrected visual acuity (BCVA) of 0.7 logMAR or better (Snellen equivalent of 20/100 or better) in each eye at Visit 1.
• At least one eye, the same eye, must satisfy all criteria for Schirmer's Test, corneal fluorescein staining, conjunctival lissamine green staining, conjunctival redness, and CAE response.
• Female participants of childbearing potential must have a negative urine pregnancy test and must use adequate birth control throughout the study period. For non-sexually active females, abstinence may be regarded as an adequate method of birth control.

Exclusion criteria

• Clinically significant slit-lamp findings at Visit 1, including active blepharitis, meibomian gland dysfunction, severe lid margin inflammation, or active ocular allergies requiring therapeutic treatment, and/or findings that in the opinion of the investigator may interfere with study parameters. Participants with moderate to severe meibomian gland dysfunction, in the opinion of the investigator, are not eligible.
• Ongoing ocular infection, including bacterial, viral, or fungal infection, or active ocular inflammation at Visit 1.
• Contact lens wear within 7 days of Visit 1 or anticipated use of contact lenses during the study.
• LASIK surgery within the last 12 months.
• Female participant who is pregnant, nursing, or planning a pregnancy.
• Female participant of childbearing potential who is unwilling to submit a urine pregnancy test at Visit 1 and Visit 4, or at an early termination visit.
• Female participant of childbearing potential who is not using an acceptable method of birth control. Acceptable methods include hormonal contraceptives, mechanical contraception with spermicide and a barrier method, intrauterine device, or surgical sterilization of partner. For non-sexually active females, abstinence may be regarded as adequate; however, if the participant becomes sexually active during the study, she must agree to use adequate birth control for the remainder of the study.
• Known allergy and/or sensitivity to the test article or its components.
• Any condition or situation that, in the investigator's opinion, may put the participant at significant risk, may confound study results, or may interfere significantly with participation in the study.
• Current enrollment in an investigational drug or device study or use of an investigational drug or device within 30 days of Visit 1.
• Unable or unwilling to follow instructions, including participation in all study assessments and visits.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Tauber J, Karpecki P, Latkany R, Luchs J, Martel J, Sall K, Raychaudhuri A, Smith V, Semba CP; OPUS-2 Investigators. Lifitegrast Ophthalmic Solution 5.0% versus Placebo for Treatment of Dry Eye Disease: Results of the Randomized Phase III OPUS-2 Study. Ophthalmology. 2015 Dec;122(12):2423-31. doi: 10.1016/j.ophtha.2015.08.001. Epub 2015 Sep 11. PMID 26365210
• Mah F, Milner M, Yiu S, Donnenfeld E, Conway TM, Hollander DA. PERSIST: Physician's Evaluation of Restasis((R)) Satisfaction in Second Trial of topical cyclosporine ophthalmic emulsion 0.05% for dry eye: a retrospective review. Clin Ophthalmol. 2012;6:1971-6. doi: 10.2147/OPTH.S30261. Epub 2012 Nov 28. PMID 23226002
• Schaumberg DA, Dana R, Buring JE, Sullivan DA. Prevalence of dry eye disease among US men: estimates from the Physicians' Health Studies. Arch Ophthalmol. 2009 Jun;127(6):763-8. doi: 10.1001/archophthalmol.2009.103. PMID 19506195
• Gayton JL. Etiology, prevalence, and treatment of dry eye disease. Clin Ophthalmol. 2009;3:405-12. doi: 10.2147/opth.s5555. Epub 2009 Jul 14. PMID 19688028
• Bron AJ, de Paiva CS, Chauhan SK, Bonini S, Gabison EE, Jain S, Knop E, Markoulli M, Ogawa Y, Perez V, Uchino Y, Yokoi N, Zoukhri D, Sullivan DA. TFOS DEWS II pathophysiology report. Ocul Surf. 2017 Jul;15(3):438-510. doi: 10.1016/j.jtos.2017.05.011. Epub 2017 Jul 20. PMID 28736340

Identifiers

NCT: NCT07625124 · RDC001_201

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗