Assess the Safety and Efficacy of CsA Ophthalmic Gel in Subjects With Dry Eye

A Phase Ⅱ, Multicenter, Randomized, Single-blind, Positive-controlled, Dose-finding Study to Assess the Efficacy and Safety of CsA Ophthalmic Gel in Subjects With Moderate to Severe Aqueous-Deficient Dry Eye (ADDE)

The purpose of this study is to explore the efficacy and safety of CsA ophthalmic gel in the treatment of moderate to severe tear deficiency dry eye with different dosage, frequency and concentration, and to preliminarily determine the optimal dosage, frequency and concentration, so as to provide a theoretical basis for the design of follow-up clinical studies.

Study Overview

• Status: Completed
• Conditions: Dry Eye
• Intervention / Treatment: Drug: CsA eye gel; Drug: Hypromellose Eye Drops; Drug: CsA for eye emulsion

Detailed Description

A multicenter, randomized, single-blind, positive controlled exploratory study will be conducted with cyclosporine A ophthalmic emulsion as the control drug.

The experimental drugs were divided into three groups:

Treatment group A: CsA eye gel: 0.3 g: 0.15 mg, once daily； Treatment group B: CsA eye gel: 0.3 g: 0.15 mg, twice daily, interval of about 12 hours； Treatment group C: CsA eye gel: 0.3 g: 0.3 mg, once daily. One drop into each eye when you use it.

Control group: CsA emulsion: 0.4 ml: 0.2 mg. One drop into the eye, 2 times daily with an interval for 12 hours.

• Study Type: Interventional
• Enrollment (Actual): 240
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Ophthalmological Center of Zhongshan University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age ≥18, both male and female;
2. Pregnancy tests were negative for women of childbearing age and contraceptive measures (including abstinence, intrauterine devices, diaphragms and spermicides) were taken during the trial. Men are willing to use approved contraceptive methods (possibly using condoms and spermicides or oral contraceptives, implants or injections of contraceptives, intrauterine devices, diaphragms and spermicides) or sexual partner infertility;

3. 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. In any area, corneal fluorescein staining was more than 2 points.
4. The anatomy of the eyelids is normal and has normal blinking function;
5. Patients with newly diagnosed dry eye disease, or who are undergoing dry eye treatment, voluntarily discontinue treatment within 72 hours of entering the screening period;
6. Ability and willingness to participate in all research assessments and all planned visits during the pilot period in accordance with the programme requirements;
7. Agree to participate in the study and voluntarily sign informed consent.

Exclusion Criteria:

1. Allergy to CsA, fluorescein or any component of the drug is known;
2. Severe dry eye patients requiring surgical treatment;
3. Glaucoma patients;
4. Unwilling to avoid wearing contact lenses;
5. Within 12 months prior to the start of the study, intraocular surgery or internal surgery was necessary;
6. Eyelid surgery was performed within 6 months prior to the start of the study, or dry eye secondary to surgery;
7. Those who had undergone corneal refractive surgery or keratoplasty;
8. Congenital lacrimal gland or meibomian gland deficiency or lacrimal gland obstructive diseases;
9. Systemic inflammation or active eye infection and blepharitis;
10. Patients with ocular cicatricial pemphigoid, obvious conjunctival scar, ocular chemical burn and neurotrophic keratoconjunctivitis;
11. Who suffered from ocular malignancies;
12. No other eye drops could be stopped during the study period;
13. Systemic or uncontrollable disorders that affect the collection of research parameters or patient compliance, such as severe cardiopulmonary disease, uncontrollable hypertension and diabetes;
14. With history of central nervous system disease or epilepsy, and / or mental disorder;
15. Pregnant women and lactating women, or women of childbearing age, do not adopt effective contraceptive measures;
16. Participated in other clinical trials or participated in other clinical trials within 1 months before the election;
17. Systemic or topical cyclosporine drugs within 3 months;
18. Patients who were not considered suitable for the study, including those who were unable or unwilling to comply with the protocol requirements.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 0.3 g: 0.15 mg（1)&Hypromellose Eye Drops; Sixty 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.	Drug: CsA eye gel; The CsA eye gel of 0.3 g: 0.15 mg, 0.3 g: 0.3 mg; Other Names: CsA gel; Drug: Hypromellose Eye Drops; Hypromellose Eye Drops of 15ml：75mg, 3 times daily, 1-2 drop; Other Names: zhenshishuang
Experimental: 0.3 g: 0.15mg（2)&Hypromellose Eye Drops; Sixty subjects will be treated with CsA eye gel: 0.3 g: 0.15 mg, 2 times daily, interval of about 12 hours, The treatment period is 12 weeks. The basic medicine is Hypromellose Eye Drops, 3 times daily for 12 weeks.	Drug: CsA eye gel; The CsA eye gel of 0.3 g: 0.15 mg, 0.3 g: 0.3 mg; Other Names: CsA gel; Drug: Hypromellose Eye Drops; Hypromellose Eye Drops of 15ml：75mg, 3 times daily, 1-2 drop; Other Names: zhenshishuang
Experimental: 0.3 g: 0.3 mg &Hypromellose Eye Drops; Sixty subjects will be treated with CsA eye gel: 0.3 g: 0.3 mg, 1 times daily, The treatment period is 12 weeks. The basic medicine is Hypromellose Eye Drops, 3 times daily for 12 weeks.	Drug: CsA eye gel; The CsA eye gel of 0.3 g: 0.15 mg, 0.3 g: 0.3 mg; Other Names: CsA gel; Drug: Hypromellose Eye Drops; Hypromellose Eye Drops of 15ml：75mg, 3 times daily, 1-2 drop; Other Names: zhenshishuang
Active Comparator: 0.4 ml: 0.2 mg &Hypromellose Eye Drops; Sixty subjects will be treated with CsA for eye emulsion: 0.4 ml: 0.2 mg, 2 times daily, interval of about 12 hours, The treatment period is 12 weeks. The basic medicine is Hypromellose Eye Drops, 3 times daily for 12 weeks.	Drug: Hypromellose Eye Drops; Hypromellose Eye Drops of 15ml：75mg, 3 times daily, 1-2 drop; Other Names: zhenshishuang; Drug: CsA for eye emulsion; The CsA for eye emulsion of 0.4 ml: 0.2 mg; Other Names: CsA emulsion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The EDS score at the NO.5 visit was compared with the baseline EDS score (binocular)	0-100 points VAS score was evaluated	84 days after admission

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
The EDS score at the NO.3, NO.4 visit were compared with the baseline EDS score (binocular)	0-100 points VAS score was evaluated	14 days after admission ，42days after admission
Comparison of the NO.3, NO.4, NO.5 visit and baseline corneal fluorescein staining changes	score（The cornea was divided into five quadrants: central, upper, lower, temporal and nasal. The cornea was stained with 4 points, 0 points for non-staining, 1 point for scattered dotted staining, 2 points for clan staining, 3 points for local dense + scattered dotted staining and 4 points for extensive diffuse staining. The total score is the sum of the quadrant scores）	14 days after admission ，42 days after admission ，84 days after admission
Comparison of the NO.3, NO.4, NO.5 visit and baseline BUT changes	time	14 days after admission ，42 days after admission ，84 days after admission
Comparison of the NO.3, NO.4, NO.5 visit and baseline Schirmer changes	Basal tear secretion	14 days after admission ，42 days after admission ，84 days after admission

Collaborators and Investigators

• Sponsor: Zhaoke (Guangzhou) Ophthalmology Pharmaceutical Ltd.
• Investigators: Study Director: shiyou zhou, PHD, Ophthalmological Center of Zhongshan University

Publications and helpful links

General Publications

• Research in dry eye: report of the Research Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf. 2007 Apr;5(2):179-93. doi: 10.1016/s1542-0124(12)70086-1.
• 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.
• 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.
• 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.
• Barr JT, Schechtman KB, Fink BA, Pierce GE, Pensyl CD, Zadnik K, Gordon MO. Corneal scarring in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study: baseline prevalence and repeatability of detection. Cornea. 1999 Jan;18(1):34-46.

Study record dates

Study Major Dates

• Study Start (Actual): May 9, 2018
• Primary Completion (Actual): June 30, 2019
• Study Completion (Actual): December 12, 2019

Study Registration Dates

• First Submitted: August 30, 2018
• First Submitted That Met QC Criteria: September 16, 2018
• First Posted (Actual): September 18, 2018

Study Record Updates

• Last Update Posted (Actual): May 8, 2020
• Last Update Submitted That Met QC Criteria: May 6, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Lacrimal Apparatus Diseases; Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases; Dry Eye Syndromes; Keratoconjunctivitis Sicca; Pharmaceutical Solutions; Ophthalmic Solutions
• Other Study ID Numbers: ZK-CSA-201704

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