3% Diquafosol Ophthalmic Solution for Active Moderate-to-Severe Vernal Keratoconjunctivitis

April 24, 2026 updated by: The University of Hong Kong

A Randomized Controlled Trial of 3% Diquafosol Ophthalmic Solution for Active Moderate-to-Severe Vernal Keratoconjunctivitis

The aim of the study is to investigate whether patients with moderate-to-severe VKC and keratitis will benefit from the addition of Diquafosol ophthalmic solution in terms of symptoms and signs of VKC, tear film metrics, ocular surface inflammation and quality of life. Potential beneficial effect of Diquafosol treatment on top of current standard use of topical immunosuppressant therapy in VKC would be studied.

Subject at least aged 6 and above with clinical diagnosis of vernal keratoconjunctivitis would be invited to join this study and perform the following assessments:

  1. best corrected visual acuity,
  2. slit lamp biomicroscope examination,
  3. tear meniscus height and non-invasive keratographic tear breakup time(NIKBUT) measurement,
  4. cornea fluorescein staining (CFS) and
  5. Schirmer's I test. Doctor will prescribe eyedrop, 3% Diquafosol ophthalmic solution and 0.1% Cyclosporin A cationic ophthalmic emulsion or 0.1% Cyclosporin A cationic ophthalmic emulsion at the end of examination. Subjects will be followed up at 4 weeks, 8 weeks, 16 weeks after treatment.

All participants will be required to answer a standardised questionnaire relating to severity of VKC and dry eye disease.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Aim To compare the four-month clinical efficacy of topical treatment with 3% Diquafosol ophthalmic solution and 0.1% Cyclosporin A cationic ophthalmic emulsion versus 0.1% Cyclosporin A cationic ophthalmic emulsion in reducing symptoms and signs of active moderate-to-severe vernal keratoconjunctivitis (grade of 2 to 4 on the Bonini severity scale) with keratitis (corneal fluorescein staining score of 1-5 on the modified Oxford scale).

Study design A single-centre prospective double-blinded randomized controlled trial

Hypothesis The addition of topical treatment with 3% Diquafosol ophthalmic solution is superior to 0.1% Cyclosporin cationic ophthalmic emulsion alone in improving symptoms and signs of moderate-to-severe VKC with keratitis at four months of use.

Methods This is a single-centre, prospective, 16-week, randomized, double-blinded controlled clinical trial investigating the clinical efficacy and safety of combined topical treatment with 3% Diquafosol ophthalmic solution and 0.1% Cyclosporin A cationic ophthalmic emulsion and versus topical treatment with 0.1% Cyclosporin A cationic ophthalmic emulsion in patients with moderate-to-severe vernal keratoconjunctivitis and keratitis. The study will also investigate the longitudinal changes in tear cytokines and correlate them with changes in VKC signs and tear film metrics. The study will be performed in accordance with the principles of the Declaration of Helsinki, the International Conference on Harmonization, Good Clinical Practice guidelines, and all applicable laws and regulations. Written informed consent will be obtained from each patient before enrolment in the study. A clinical trials certificate will be obtained from the Department of Health, Hong Kong SAR.

Sample size The study will recruit 94 subjects with moderate-to-severe VKC at eye clinics in Hong Kong West cluster (QMH and GH).

Sample size Calculation Sample size calculation is based on the findings from a prospective study comparing the combined use of 3% Diquafosol and 0.1% Cyclosporin versus 0.1% Cyclosporin alone in the treatment of dry eye disease in 279 subjects [36]. It is anticipated that a similar, if not larger, effective size in VKC patients compared to dry eye patients would be seen. In this study the mean change in cornea staining score between baseline and week 12 was significantly higher in Cyclosporin A and Diquafosol combination therapy (2.91 ± 3.93) than in Cyclosporin A monotherapy (0.93± 2.22). The estimated Cohen's d for this study is approximately 0.620. Based on calculations, approximately 41 participants per group to achieve a study power of 80% with a significance level of 0.05 and the estimated effect size of 0.620 is needed. Considering a 10% dropout rate, the adjusted sample size per group would be approximately 47 participants.

Randomization method Randomisation is conducted by computer-generated random number allocation and will be applied to sequentially enrolled participants. The randomisation schedule is pre-determined, prior to commencing participant recruitment, such that the investigator involved in baseline participant assessment will have no involvement in treatment allocation. Block randomization is performed to ensure 1:1 distribution into treatment groups.

Double-blinding To keep the investigators and subjects blind to the study treatment, all investigational drugs are removed from their commercial packaging, wrapped in aluminium foil, double-wrapped in plastic bags, and distributed to participants by an independent clinical research coordinator.

Rescue Therapy During the study period rescue medication (Loteprednolol 0.5% one drop 4x/day for up to 5 days) is permitted in the event of worsening of ocular surface symptoms. A maximum of 2 courses were allowed between study visits. Any use of rescue therapy is documented in the eyedrop diary and serves as one of the outcome measures.

Patient Workflow The patient workflow is aimed at obtaining clear and comprehensive documentation of symptoms and signs baseline and each subsequent visit after initiation of intervention. Furthermore, documentation of adverse events is achieved via assessment of best corrected visual acuity, intraocular pressure measurement, general periorbital area assessment and slit lamp biomicroscope assessment. See Figure 1. Study Workflow

In particular, the sequence of clinical assessments must be done in order of sequence from least invasive to most invasive, as any touching of the ocular surface or manipulation of the eyelids will stimulate tear secretion. Least invasive tests include imaging-based assessments without manipulation or touching of the ocular surface, include best corrected visual acuity, slit lamp biomicroscope assessment, NIKBUT and tear meniscus height. Mildly invasive tests include those that require gentle touching of the ocular surface, such as fluorescein cornea staining. Moderately invasive tests include those with prolonged ocular surface contact, such as the Schirmer's I test for tear collection

Study Type

Interventional

Enrollment (Estimated)

94

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Kendrick Co Shih
  • Phone Number: 39621412
  • Email: kcshih@hku.hk

Study Locations

  • Hong Kong
      • Hong Kong, Hong Kong
        • Recruiting
        • HKU Eye Centre
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Subject at least aged 6 and above
  • Clinical diagnosis of vernal keratoconjunctivitis
  • Evidence of active moderate-to-severe disease: At least Grade 2 on the Bonini scale of VKC clinical presentation (moderate-to-severe) [38].
  • Evidence of keratitis: At least Grade 1 on the Modified Oxford scale for cornea fluorescein staining as reported by Bron et al [39].
  • Experienced 1 or more recurrences of VKC during the previous year

Exclusion Criteria:

  • Nasolacrimal duct obstruction
  • Impaired blinking function
  • Active ocular infection or history of ocular herpes, varicella zoster or vaccinia virus infection
  • Any ocular disease that would require topical ocular treatment during the study
  • Use of cyclosporin A or tacrolimus eyedrops, or use of systemic immunosuppressants within 3 months before enrolment
  • Any ocular surgery within 6 months before enrolment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 3% Diquafosol ophthalmic solution and 0.1% Cyclosporin A cationic ophthalmic emulsion
3% Diquafosol eyedrops 6x/day + 0.1% Cyclosporin A twice a day
Drug: 3% Diquafosol ophthalmic solution and 0.1% Cyclosporin A cationic ophthalmic emulsion
This arm is to investigate whether patients with moderate-to-severe VKC and keratitis will benefit from the addition of Diquafosol ophthalmic solution
Active Comparator: 0.1% Cyclosporin A cationic ophthalmic emulsion
0.1% Cyclosporin A eyedrops twice a day + preservative free sodium hyaluronate eyedrops 6x/day
Drug: 0.1% Cyclosporin A cationic ophthalmic emulsion
This arm is a control group to investigate whether patients with moderate-to-severe VKC and keratitis will benefit from the addition of Diquafosol ophthalmic solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Cornea Fluorescein Staining (CFS) score from baseline to 4 weeks, 8 weeks and 16 weeks between study groups
Time Frame: From baseline to 4 months post- treatment between study groups
Higher values mean inferior outcomes. Graded according to the modified Oxford grading scale (range 0, 0.5, 1, 2, 3, 4, 5). A difference in score of at least 2 levels (i.e. 4 to 2) or complete resolution of staining (i.e. 0) are both considered clinically significant endpoints.
From baseline to 4 months post- treatment between study groups

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of patients requiring rescue topical steroid therapy at 4 weeks, 8 weeks and 16 weeks
Time Frame: From baseline to 4 months post- treatment between study groups
Number of patients requiring rescue topical steroid therapy divided by all patients participated in this study
From baseline to 4 months post- treatment between study groups
Change in best corrected visual acuity from baseline to 4 weeks, 8 weeks and 16 weeks
Time Frame: From baseline to 4 months post- treatment between study groups
From logmar(1.0 to -0.1)
From baseline to 4 months post- treatment between study groups
Change in NIKBUT from baseline to 4 weeks, 8 weeks and 16 weeks
Time Frame: From baseline to 4 months post- treatment between study groups
NIKBUT is measured in seconds and average of 3 consecutive readings is taken. Higher values mean better outcomes.
From baseline to 4 months post- treatment between study groups
Change in tear meniscus height from baseline to 4 weeks, 8 weeks and 16 weeks
Time Frame: From baseline to 4 months post- treatment between study groups
In millimetres. Readings serve as objective parameters for tear volume
From baseline to 4 months post- treatment between study groups
Change in tear cytokines from baseline to 4 weeks, 8 weeks and 16 weeks
Time Frame: From baseline to 4 months post- treatment between study groups
Percentage change in tear cytokines analysis done in lab
From baseline to 4 months post- treatment between study groups
Percentage of patients with improvement in Cornea Fluorescein Staining (CSF) at 4 weeks, 8 weeks and 16 weeks
Time Frame: From baseline to 4 months post- treatment between study groups
Number of patients with improvement in CFS requiring rescue topical steroid therapy divided by all patients participated in this study
From baseline to 4 months post- treatment between study groups
Change in Standard Patient Evaluation of Eye Dryness Questionnaire (SPEED) score from baseline to 4 weeks, 8 weeks and 16 weeks
Time Frame: From baseline to 4 months post- treatment between study groups
Range from 0-28, one mark was collected per patient, with higher scores meaning worse
From baseline to 4 months post- treatment between study groups
Change in Quality of Life in Children with Vernal Keratoconjunctivitis (QUICK) score from baseline to 4 weeks, 8 weeks and 16 weeks
Time Frame: From baseline to 4 months post- treatment between study groups
Range from 0-48, one mark was collected per patient, with higher scores meaning worse outcomes
From baseline to 4 months post- treatment between study groups

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of ocular adverse events
Time Frame: From baseline to 4 months post- treatment between study groups
Number of patients with ocular adverse events divided by all patients participated in this study
From baseline to 4 months post- treatment between study groups
Incidence of non-ocular adverse events
Time Frame: From baseline to 4 months post- treatment between study groups
Number of patients with non-ocular adverse events divided by all patients participated in this study
From baseline to 4 months post- treatment between study groups
• Incremental cost-effectiveness ratio (ICER) in cost per quality-adjusted life year (QALYs) gained.
Time Frame: From baseline to 4 months post- treatment between study groups
It is defined by the difference in cost between two possible interventions, divided by the difference in their effect.
From baseline to 4 months post- treatment between study groups

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The University of Hong Kong

Investigators

  • Principal Investigator: Kendrick Co Shih, The University of Hong Kong, Grantham Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 9, 2026

Primary Completion (Estimated)

June 30, 2028

Study Completion (Estimated)

December 31, 2028

Study Registration Dates

First Submitted

March 25, 2025

First Submitted That Met QC Criteria

March 25, 2025

First Posted (Actual)

April 1, 2025

Study Record Updates

Last Update Posted (Actual)

April 30, 2026

Last Update Submitted That Met QC Criteria

April 24, 2026

Last Verified

April 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VKC001

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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