Clinical trial NCT03676335: Assess the Safety and Efficacy of CsA Ophthalmic Gel in Subjects With Dry Eye
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Dry Eye
Lead sponsor: Zhaoke (Guangzhou) Ophthalmology Pharmaceutical Ltd.
Sponsor class: INDUSTRY
First posted: 2018-09-18
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The EDS score at the NO.5 visit was compared with the baseline EDS score (binocular)
timeFrame: 84 days after admission
Secondary outcomes:
measure: The EDS score at the NO.3, NO.4 visit were compared with the baseline EDS score (binocular)
timeFrame: 14 days after admission ，42days after admission
measure: 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)
timeFrame: 14 days after admission ，42 days after admission ，84days days after admission
measure: Comparison of the NO.3, NO.4, NO.5 visit and baseline corneal fluorescein staining changes
timeFrame: 14 days after admission ，42 days after admission ，84 days after admission
measure: Comparison of the NO.3, NO.4, NO.5 visit and baseline BUT changes
timeFrame: 14 days after admission ，42 days after admission ，84 days after admission
measure: Comparison of the NO.3, NO.4, NO.5 visit and baseline Schirmer changes
timeFrame: 14 days after admission ，42 days after admission ，84 days after admission
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Ophthalmological Center of Zhongshan University
state: Guangdong
Study officials:
affiliation: Ophthalmological Center of Zhongshan University
name: shiyou zhou, PHD
role: STUDY_DIRECTOR
References:
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.
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.
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.
citation: 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.
citation: 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.