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Assess the Safety and Efficacy of CsA Ophthalmic Gel in Subjects With Moderate to Severe Dry Eye Disease

Primary Purpose

Dry Eye

Status

Completed

Phase

Phase 3

Locations

China

Study Type

Interventional

Intervention

CsA Ophthalmic Gel

Placebo

Hypromellose Eye Drop

About this trial

This is an interventional treatment trial for Dry Eye

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

1）18≤Age≤80, both male and female 2）According to the symptoms and signs and ophthalmologic examinations, the patients were diagnosed as moderate to severe dry eye

EDS score is more than 40 points;
BUT is less than 10 s;
Schirmer test result is less than 10mm/5 min;
ICSS≥2 points. 3）The ICSS score of baseline decreased by≤ 20% compared with that of screening period 4）Agree to participate in the study and voluntarily sign informed consent.

Exclusion Criteria:

Severe dry eye patients requiring surgical treatment
Had inner eye surgery within 12 months prior to screening or required inner eye surgery during the study period;Eyelid surgery was performed within 6 months prior to screening
Patients receiving permanent lacrimal insertion or patients receiving temporary lacrimal insertion within 6 months prior to screening;
Operation-induced dry eye
Glaucoma patients;
Unwilling to avoid wearing contact lenses;
Systemic inflammation or active eye infection and blepharitis;
Patients with multiple episodes of viral keratitis
Patients with ocular cicatricial pemphigoid, obvious conjunctival scar, ocular chemical burn and neurotrophic keratoconjunctivitis
Patients with malignant tumors in the past 5 years, except the thoroughly cured basal cell carcinoma of skin, squamous cell carcinoma in situ of skin, and primordial cervical cancer;
Perimenopausal women are taking hormone replacement therapy
Patients who cannot stop using other eye drops and other ophthalmic preparations during the study period;
Patients with severe cardiopulmonary diseases, uncontrolled hypertension and diabetes, etc. that affect the collection or compliance of study parameters;
ALT and AST ≥ 2 times of the normal upper limit, and serum creatinine ≥ 1.5 times of the normal upper limit
With a history of central nervous system disease or epilepsy, and/or a mental state that does not cooperate
Pregnant women and lactating women, or women of childbearing age, do not adopt effective contraceptive measures;
Participated in other clinical trials or participated in other clinical trials within 1 months before the election;
Systemic or topical cyclosporine drugs within 1 months before the election;
Allergy to CsA, fluorescein or any component of the drug is known；
Patients who were not considered suitable for the study, including those who were unable or unwilling to comply with the protocol requirements.

Sites / Locations

Ophthalmological Center of Zhongshan University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Experimental Group

Control group

Arm Description

322 subjects will be treated with CsA eye gel: 0.3 g: 0.15 mg, 1 times daily, The treatment period is 12 weeks. The basic medicine is Hypromellose Eye Drops, 3 times daily for 12 weeks.

322 subjects will be treated with Placebo : 0 g: 0mg, 1 times daily, The treatment period is 12 weeks. The basic medicine is Hypromellose Eye Drops, 3 times daily for 12 weeks.

Outcomes

Primary Outcome Measures

Proportion of patients whose corneal fluorescein staining score (ICSS) decreased by ≥1 point from baseline at visit 5 (study eye)

ICSS：no staining = 0，few/rare punctate lesions = 1，discrete and countable lesions = 2，lesions too numerous to count，but not coalescent = 3，coalescent = 4

Secondary Outcome Measures

EDS score at the NO.3, NO.4 and NO.5 visit was compared with the baseline EDS score (binocular)

0-100 points VAS score was evaluated

Average changes in VAS scores of 6 dry eye symptoms (burning/needling sensation, pruritus, foreign body sensation, discomfort, photophobia and pain) at the NO.3, NO.4 and NO.5 visit were compared with baseline (binocular)

0-100 points VAS score was evaluated

corneal fluorescein staining score (ICSS)at the NO.3, NO.4 and NO.5 visit was compared with the baseline (binocular)

ICSS：no staining = 0，few/rare punctate lesions = 1，discrete and countable lesions = 2，lesions too numerous to count，but not coalescent = 3，coalescent = 4

oxford score at the NO.3, NO.4 and NO.5 visit was compared with the baseline (binocular)

0~V grade was evaluated

Tear break-up time(BUT) at the NO.3, NO.4 and NO.5 visit was compared with the baseline (binocular)

The time taken for the first dry spot to appear on the cornea after a complete blink with fluorescein

Schirmer's II test (with anesthetic) at the NO.3, NO.4 and NO.5 visit was compared with the baseline (binocular)

Basal tear secretion with topical anesthesia, determined by the moisture length on the filter paper in 5 minutes

Full Information

NCT ID

NCT04541888

First Posted

August 27, 2020

Last Updated

April 21, 2022

Sponsor

Zhaoke (Guangzhou) Ophthalmology Pharmaceutical Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT04541888

Brief Title

Assess the Safety and Efficacy of CsA Ophthalmic Gel in Subjects With Moderate to Severe Dry Eye Disease

Official Title

A Phase 3, Multicenter, Randomized, Double-blind, Vehicle-controlled Efficacy and Safety Study of CsA Ophthalmic Gel in Subjects With Moderate to Severe Dry Eye Disease

Study Type

Interventional

2. Study Status

Record Verification Date

April 2022

Overall Recruitment Status

Completed

Study Start Date

November 5, 2020 (Actual)

Primary Completion Date

August 16, 2021 (Actual)

Study Completion Date

October 14, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Zhaoke (Guangzhou) Ophthalmology Pharmaceutical Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this study is to explore the efficacy and safety of CsA ophthalmic gel in the treatment of moderate to severe dry eye disease .

Detailed Description

A multicenter,randomized, double-blind, vehicle-controlled Study.Subjects will be randomly assigned to the experimental group and the control group,experimental group: CsA eye gel: 0.3 g: 0.15 mg, once daily;One drop into each eye when you use it.hypromellose eye drops:10ml：50mg,three times a day Control group: vehicle. One drop into the eye, once daily;One drop into each eye when you use it.hypromellose eye drops:10ml：50mg,three times a day

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Dry Eye

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

644 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Experimental Group

Arm Type

Experimental

Arm Description

322 subjects will be treated with CsA eye gel: 0.3 g: 0.15 mg, 1 times daily, The treatment period is 12 weeks. The basic medicine is Hypromellose Eye Drops, 3 times daily for 12 weeks.

Arm Title

Control group

Arm Type

Placebo Comparator

Arm Description

322 subjects will be treated with Placebo : 0 g: 0mg, 1 times daily, The treatment period is 12 weeks. The basic medicine is Hypromellose Eye Drops, 3 times daily for 12 weeks.

Intervention Type

Drug

Intervention Name(s)

CsA Ophthalmic Gel

Other Intervention Name(s)

CsA gel

Intervention Description

The CsA eye gel of 0.3 g: 0.15 mg

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo

Intervention Type

Drug

Intervention Name(s)

Hypromellose Eye Drop

Other Intervention Name(s)

zhenshishuang

Intervention Description

Hypromellose Eye Drops of 10ml：50mg, 3 times daily, 1-2 drop

Primary Outcome Measure Information:

Title

Proportion of patients whose corneal fluorescein staining score (ICSS) decreased by ≥1 point from baseline at visit 5 (study eye)

Description

ICSS：no staining = 0，few/rare punctate lesions = 1，discrete and countable lesions = 2，lesions too numerous to count，but not coalescent = 3，coalescent = 4

Time Frame

84 days after admission

Secondary Outcome Measure Information:

Title

EDS score at the NO.3, NO.4 and NO.5 visit was compared with the baseline EDS score (binocular)

Description

0-100 points VAS score was evaluated

Time Frame

14 days after admission ，42 days after admission ，84days days after admission

Title

Description

0-100 points VAS score was evaluated

Time Frame

14 days after admission ，42 days after admission ，84days days after admission

Title

corneal fluorescein staining score (ICSS)at the NO.3, NO.4 and NO.5 visit was compared with the baseline (binocular)

Description

ICSS：no staining = 0，few/rare punctate lesions = 1，discrete and countable lesions = 2，lesions too numerous to count，but not coalescent = 3，coalescent = 4

Time Frame

14 days after admission ，42 days after admission ，84days days after admission

Title

oxford score at the NO.3, NO.4 and NO.5 visit was compared with the baseline (binocular)

Description

0~V grade was evaluated

Time Frame

14 days after admission ，42 days after admission ，84days days after admission

Title

Tear break-up time(BUT) at the NO.3, NO.4 and NO.5 visit was compared with the baseline (binocular)

Description

The time taken for the first dry spot to appear on the cornea after a complete blink with fluorescein

Time Frame

14 days after admission，42 days after admission ，84days days after admission

Title

Schirmer's II test (with anesthetic) at the NO.3, NO.4 and NO.5 visit was compared with the baseline (binocular)

Description

Basal tear secretion with topical anesthesia, determined by the moisture length on the filter paper in 5 minutes

Time Frame

14 days after admission ，42 days after admission ，84days days after admission

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 1）18≤Age≤80, both male and female 2）According to the symptoms and signs and ophthalmologic examinations, the patients were diagnosed as moderate to severe dry eye EDS score is more than 40 points; BUT is less than 10 s; Schirmer test result is less than 10mm/5 min; ICSS≥2 points. 3）The ICSS score of baseline decreased by≤ 20% compared with that of screening period 4）Agree to participate in the study and voluntarily sign informed consent. Exclusion Criteria: Severe dry eye patients requiring surgical treatment Had inner eye surgery within 12 months prior to screening or required inner eye surgery during the study period;Eyelid surgery was performed within 6 months prior to screening Patients receiving permanent lacrimal insertion or patients receiving temporary lacrimal insertion within 6 months prior to screening; Operation-induced dry eye Glaucoma patients; Unwilling to avoid wearing contact lenses; Systemic inflammation or active eye infection and blepharitis; Patients with multiple episodes of viral keratitis Patients with ocular cicatricial pemphigoid, obvious conjunctival scar, ocular chemical burn and neurotrophic keratoconjunctivitis Patients with malignant tumors in the past 5 years, except the thoroughly cured basal cell carcinoma of skin, squamous cell carcinoma in situ of skin, and primordial cervical cancer; Perimenopausal women are taking hormone replacement therapy Patients who cannot stop using other eye drops and other ophthalmic preparations during the study period; Patients with severe cardiopulmonary diseases, uncontrolled hypertension and diabetes, etc. that affect the collection or compliance of study parameters; ALT and AST ≥ 2 times of the normal upper limit, and serum creatinine ≥ 1.5 times of the normal upper limit With a history of central nervous system disease or epilepsy, and/or a mental state that does not cooperate Pregnant women and lactating women, or women of childbearing age, do not adopt effective contraceptive measures; Participated in other clinical trials or participated in other clinical trials within 1 months before the election; Systemic or topical cyclosporine drugs within 1 months before the election; Allergy to CsA, fluorescein or any component of the drug is known； Patients who were not considered suitable for the study, including those who were unable or unwilling to comply with the protocol requirements.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

shiyou zhou, PHD

Organizational Affiliation

Ophthalmological Center of Zhongshan University

Official's Role

Study Director

Facility Information:

Facility Name

Ophthalmological Center of Zhongshan University

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510060

Country

China

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

20735287

Citation

Utine CA, Stern M, Akpek EK. Clinical review: topical ophthalmic use of cyclosporin A. Ocul Immunol Inflamm. 2010 Oct;18(5):352-61. doi: 10.3109/09273948.2010.498657.

Results Reference

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PubMed Identifier

11879137

Citation

Kunert KS, Tisdale AS, Gipson IK. Goblet cell numbers and epithelial proliferation in the conjunctiva of patients with dry eye syndrome treated with cyclosporine. Arch Ophthalmol. 2002 Mar;120(3):330-7. doi: 10.1001/archopht.120.3.330. Erratum In: Arch Ophthalmol 2002 Aug;120(8):1099.

Results Reference

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PubMed Identifier

15604871

Citation

Strong B, Farley W, Stern ME, Pflugfelder SC. Topical cyclosporine inhibits conjunctival epithelial apoptosis in experimental murine keratoconjunctivitis sicca. Cornea. 2005 Jan;24(1):80-5. doi: 10.1097/01.ico.0000133994.22392.47.

Results Reference

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PubMed Identifier

16371776

Citation

Perry HD, Doshi-Carnevale S, Donnenfeld ED, Solomon R, Biser SA, Bloom AH. Efficacy of commercially available topical cyclosporine A 0.05% in the treatment of meibomian gland dysfunction. Cornea. 2006 Feb;25(2):171-5. doi: 10.1097/01.ico.0000176611.88579.0a.

Results Reference

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PubMed Identifier

29545413

Citation

Leonardi A, Messmer EM, Labetoulle M, Amrane M, Garrigue JS, Ismail D, Sainz-de-la-Maza M, Figueiredo FC, Baudouin C. Efficacy and safety of 0.1% ciclosporin A cationic emulsion in dry eye disease: a pooled analysis of two double-masked, randomised, vehicle-controlled phase III clinical studies. Br J Ophthalmol. 2019 Jan;103(1):125-131. doi: 10.1136/bjophthalmol-2017-311801. Epub 2018 Mar 15.

Results Reference

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PubMed Identifier

18848318

Citation

Kim EC, Choi JS, Joo CK. A comparison of vitamin a and cyclosporine a 0.05% eye drops for treatment of dry eye syndrome. Am J Ophthalmol. 2009 Feb;147(2):206-213.e3. doi: 10.1016/j.ajo.2008.08.015. Epub 2008 Oct 9.

Results Reference

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PubMed Identifier

28079022

Citation

Holland EJ, Luchs J, Karpecki PM, Nichols KK, Jackson MA, Sall K, Tauber J, Roy M, Raychaudhuri A, Shojaei A. Lifitegrast for the Treatment of Dry Eye Disease: Results of a Phase III, Randomized, Double-Masked, Placebo-Controlled Trial (OPUS-3). Ophthalmology. 2017 Jan;124(1):53-60. doi: 10.1016/j.ophtha.2016.09.025. Epub 2016 Oct 27.

Results Reference

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PubMed Identifier

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Citation

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.

Results Reference

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PubMed Identifier

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Citation

Bron AJ, Evans VE, Smith JA. Grading of corneal and conjunctival staining in the context of other dry eye tests. Cornea. 2003 Oct;22(7):640-50. doi: 10.1097/00003226-200310000-00008.

Results Reference

result

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Assess the Safety and Efficacy of CsA Ophthalmic Gel in Subjects With Moderate to Severe Dry Eye Disease

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