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

Dry Eye Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04541888
• Other study ID #: ZKY-CSA-202001
• Status: Completed
• Phase: Phase 3
• Start date: November 5, 2020
• Est. completion date: October 14, 2021

Study information

• Verified date: April 2022
• Source: Zhaoke (Guangzhou) Ophthalmology Pharmaceutical Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 .

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 644
• Est. completion date: October 14, 2021
• Est. primary completion date: August 16, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

1. EDS score is more than 40 points;

2. BUT is less than 10 s;

3. Schirmer test result is less than 10mm/5 min;

4. 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:

1. Severe dry eye patients requiring surgical treatment

2. 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

3. Patients receiving permanent lacrimal insertion or patients receiving temporary lacrimal insertion within 6 months prior to screening;

4. Operation-induced dry eye

5. Glaucoma patients;

6. Unwilling to avoid wearing contact lenses;

7. Systemic inflammation or active eye infection and blepharitis;

8. Patients with multiple episodes of viral keratitis

9. Patients with ocular cicatricial pemphigoid, obvious conjunctival scar, ocular chemical burn and neurotrophic keratoconjunctivitis

10. 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;

11. Perimenopausal women are taking hormone replacement therapy

12. Patients who cannot stop using other eye drops and other ophthalmic preparations during the study period;

13. Patients with severe cardiopulmonary diseases, uncontrolled hypertension and diabetes, etc. that affect the collection or compliance of study parameters;

14. ALT and AST = 2 times of the normal upper limit, and serum creatinine = 1.5 times of the normal upper limit

15. With a history of central nervous system disease or epilepsy, and/or a mental state that does not cooperate

16. Pregnant women and lactating women, or women of childbearing age, do not adopt effective contraceptive measures;

17. Participated in other clinical trials or participated in other clinical trials within 1 months before the election;

18. Systemic or topical cyclosporine drugs within 1 months before the election;

19. Allergy to CsA, fluorescein or any component of the drug is known;

20. Patients who were not considered suitable for the study, including those who were unable or unwilling to comply with the protocol requirements.

Related Conditions & MeSH terms

• Dry Eye
• Dry Eye Syndromes
• Eye Diseases
• Keratoconjunctivitis Sicca

Intervention

Drug:
• CsA Ophthalmic Gel
The CsA eye gel of 0.3 g: 0.15 mg
• Placebo
Placebo
• Hypromellose Eye Drop
Hypromellose Eye Drops of 10ml:50mg, 3 times daily, 1-2 drop

Locations

Country	Name	City	State
China	Ophthalmological Center of Zhongshan University	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Zhaoke (Guangzhou) Ophthalmology Pharmaceutical Ltd.

Country where clinical trial is conducted

China, 

References & Publications (9)

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. Review. — View 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). Ophthalmo — View 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. — View 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. Erratum in: Arch Ophthalmol 2002 Aug;120(8):1099. — View 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, vehic — View 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. — View 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. — View 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. Op — View 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	84 days after admission
Secondary	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	14 days after admission ,42 days after admission ,84days days after admission
Secondary	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	14 days after admission ,42 days after admission ,84days days after admission
Secondary	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	14 days after admission ,42 days after admission ,84days days after admission
Secondary	oxford score at the NO.3, NO.4 and NO.5 visit was compared with the baseline (binocular)	0~V grade was evaluated	14 days after admission ,42 days after admission ,84days days after admission
Secondary	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	14 days after admission,42 days after admission ,84days days after admission
Secondary	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	14 days after admission ,42 days after admission ,84days days after admission