Vernal KeratoconjunctivitisPhase 3NCT06903884
3% Diquafosol Ophthalmic Solution for Active Moderate-to-Severe Vernal Keratoconjunctivitis
A Phase 3 study testing 3% Diquafosol ophthalmic solution and 0.1% Cyclosporin A cationic ophthalmic emulsion and 0.1% Cyclosporin A cationic ophthalmic emulsion in people with Vernal Keratoconjunctivitis, run by The University of Hong Kong at 1 site in Hong Kong.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 6 years and older
- Conditions the study is for
- Vernal Keratoconjunctivitis
- What is being tested?
- 3% Diquafosol ophthalmic solution and 0.1% Cyclosporin A cationic ophthalmic emulsion and 0.1% Cyclosporin A cationic ophthalmic emulsion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 94 participants
- Where
- 1 siteHong Kong
- Study dates
- 9 Feb 2026to 31 Dec 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Hong Kong1 site, 1 recruiting
- Recruiting
HKU Eye Centre
Hong Kong
Kendrick Co SHIH, 94326271, kcshih@hku.hk
About this study
Official title: 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:
Read more
- best corrected visual acuity,
- slit lamp biomicroscope examination,
- tear meniscus height and non-invasive keratographic tear breakup time(NIKBUT) measurement,
- cornea fluorescein staining (CFS) and
- 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.
Read the 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
- Conditions
- Vernal Keratoconjunctivitis
- Being tested
- 3% Diquafosol ophthalmic solution and 0.1% Cyclosporin A cationic ophthalmic emulsion, 0.1% Cyclosporin A cationic ophthalmic emulsion
- Keywords
- Vernal Keratoconjunctivitis, Dry eye disease, Diquafosol, 0.1% Cyclosporin A
- Medical subject headings
- Conjunctivitis, Allergic, Dry Eye Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
3% Diquafosol ophthalmic solution and 0.1% Cyclosporin A cationic ophthalmic emulsionDrug
This arm is to investigate whether patients with moderate-to-severe VKC and keratitis will benefit from the addition of Diquafosol ophthalmic solution
0.1% Cyclosporin A cationic ophthalmic emulsionDrug
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
| Study group | Role | What they receive |
|---|---|---|
| 3% Diquafosol ophthalmic solution and 0.1% Cyclosporin A cationic ophthalmic emulsion | Experimental | 3% Diquafosol eyedrops 6x/day + 0.1% Cyclosporin A twice a day Receives: Drug: 3% Diquafosol ophthalmic solution and 0.1% Cyclosporin A cationic ophthalmic emulsion |
| 0.1% Cyclosporin A cationic ophthalmic emulsion | Active comparator | 0.1% Cyclosporin A eyedrops twice a day + preservative free sodium hyaluronate eyedrops 6x/day Receives: Drug: 0.1% Cyclosporin A cationic ophthalmic emulsion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Cornea Fluorescein Staining (CFS) score from baseline to 4 weeks, 8 weeks and 16 weeks 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.
Measured: From baseline to 4 months post- treatment between study groups
Secondary outcomes (8)
Percentage of patients requiring rescue topical steroid therapy at 4 weeks, 8 weeks and 16 weeks
Number of patients requiring rescue topical steroid therapy divided by all patients participated in this study
Measured: 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
Number of patients with improvement in CFS requiring rescue topical steroid therapy divided by all patients participated in this study
Measured: 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
From logmar(1.0 to -0.1)
Measured: 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
Range from 0-28, one mark was collected per patient, with higher scores meaning worse
Measured: 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
Range from 0-48, one mark was collected per patient, with higher scores meaning worse outcomes
Measured: From baseline to 4 months post- treatment between study groups
Change in NIKBUT from baseline to 4 weeks, 8 weeks and 16 weeks
NIKBUT is measured in seconds and average of 3 consecutive readings is taken. Higher values mean better outcomes.
Measured: 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
In millimetres. Readings serve as objective parameters for tear volume
Measured: From baseline to 4 months post- treatment between study groups
Change in tear cytokines from baseline to 4 weeks, 8 weeks and 16 weeks
Percentage change in tear cytokines analysis done in lab
Measured: From baseline to 4 months post- treatment between study groups
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2025
- Study start9 Feb 2026
- Primary completion30 Jun 2028 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (39)Papers the sponsor has linked to this study.
- Other trials for Vernal KeratoconjunctivitisStudies of the same condition, open and under way.
- More trials run by The University of Hong KongThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- One group of subjects will receive topical treatment with 3% Diquafosol ophthalmic solution and 0.1% Cyclosporin A cationic ophthalmic emulsion; another group of subjects will receive 0.1% Cyclosporin A cationic ophthalmic emulsion
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 94 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The University of Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kendrick Co Shih, Principal investigator, The University of Hong Kong, Grantham Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06903884
- Sponsor's protocol ID
- VKC001
- Status last verified
- Apr 2025
- First submitted
- 25 Mar 2025
- Last updated
- 30 Apr 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Biermann J, Bosche F, Eter N, Beisse F. Treating Severe Pediatric Keratoconjunctivitis with Topical Cyclosporine A. Klin Monbl Augenheilkd. 2022 Nov;239(11):1374-1380. doi: 10.1055/a-1556-1182. Epub 2021 Nov 3. English, German.
PubMed 34731901Bleik JH, Tabbara KF. Topical cyclosporine in vernal keratoconjunctivitis. Ophthalmology. 1991 Nov;98(11):1679-84. doi: 10.1016/s0161-6420(91)32069-4.
PubMed 1800929Bremond-Gignac D, Doan S, Amrane M, Ismail D, Montero J, Nemeth J, Aragona P, Leonardi A; VEKTIS Study Group. Twelve-Month Results of Cyclosporine A Cationic Emulsion in a Randomized Study in Patients With Pediatric Vernal Keratoconjunctivitis. Am J Ophthalmol. 2020 Apr;212:116-126. doi: 10.1016/j.ajo.2019.11.020. Epub 2019 Nov 23.
PubMed 31770513Coban-Karatas M, Ozkale Y, Altan-Yaycioglu R, Sizmaz S, Pelit A, Metindogan S, Canturk-Ugurbas S, Aydin-Akova Y. Efficacy of topical 0.05% cyclosporine treatment in children with severe vernal keratoconjunctivitis. Turk J Pediatr. 2014 Jul-Aug;56(4):410-7.
PubMed 25818961De Smedt S, Nkurikiye J, Fonteyne Y, Tuft S, De Bacquer D, Gilbert C, Kestelyn P. Topical ciclosporin in the treatment of vernal keratoconjunctivitis in Rwanda, Central Africa: a prospective, randomised, double-masked, controlled clinical trial. Br J Ophthalmol. 2012 Mar;96(3):323-8. doi: 10.1136/bjophthalmol-2011-300415. Epub 2011 Oct 14.
PubMed 22001151Gupta V, Sahu PK. Topical cyclosporin A in the management of vernal keratoconjunctivitis. Eye (Lond). 2001 Feb;15(Pt 1):39-41. doi: 10.1038/eye.2001.10.
PubMed 11318292Keklikci U, Dursun B, Cingu AK. Topical cyclosporine a 0.05% eyedrops in the treatment of vernal keratoconjunctivitis - randomized placebo-controlled trial. Adv Clin Exp Med. 2014 May-Jun;23(3):455-61. doi: 10.17219/acem/37145.
PubMed 24979519Labcharoenwongs P, Jirapongsananuruk O, Visitsunthorn N, Kosrirukvongs P, Saengin P, Vichyanond P. A double-masked comparison of 0.1% tacrolimus ointment and 2% cyclosporine eye drops in the treatment of vernal keratoconjunctivitis in children. Asian Pac J Allergy Immunol. 2012 Sep;30(3):177-84.
PubMed 23156846Al-Amri AM, Mirza AG, Al-Hakami AM. Tacrolimus Ointment for Treatment of Vernal Keratoconjunctivitis. Middle East Afr J Ophthalmol. 2016 Jan-Mar;23(1):135-8. doi: 10.4103/0974-9233.164616.
PubMed 26957853Al-Amri AM, Fiorentini SF, Albarry MA, Bamahfouz AY. Long-term use of 0.003% tacrolimus suspension for treatment of vernal keratoconjunctivitis. Oman J Ophthalmol. 2017 Sep-Dec;10(3):145-149. doi: 10.4103/ojo.OJO_232_2014.
PubMed 29118487Caputo R, Marziali E, de Libero C, Di Grande L, Danti G, Virgili G, Villani E, Mori F, Bacci GM, Lucenteforte E, Pucci N. Long-Term Safety and Efficacy of Tacrolimus 0.1% in Severe Pediatric Vernal Keratoconjunctivitis. Cornea. 2021 Nov 1;40(11):1395-1401. doi: 10.1097/ICO.0000000000002751.
PubMed 34029239Chatterjee S, Agrawal D. Tacrolimus in Corticosteroid-Refractory Vernal Keratoconjunctivitis. Cornea. 2016 Nov;35(11):1444-1448. doi: 10.1097/ICO.0000000000000918.
PubMed 27310883Chen M, Wei A, Ke B, Zou J, Gong L, Wang Y, Zhang C, Xu J, Yin J, Hong J. Combination of 0.05% Azelastine and 0.1% Tacrolimus Eye Drops in Children With Vernal Keratoconjunctivitis: A Prospective Study. Front Med (Lausanne). 2021 Sep 17;8:650083. doi: 10.3389/fmed.2021.650083. eCollection 2021.
PubMed 34604246Fukushima A, Ohashi Y, Ebihara N, Uchio E, Okamoto S, Kumagai N, Shoji J, Takamura E, Nakagawa Y, Namba K, Fujishima H, Miyazaki D. Therapeutic effects of 0.1% tacrolimus eye drops for refractory allergic ocular diseases with proliferative lesion or corneal involvement. Br J Ophthalmol. 2014 Aug;98(8):1023-7. doi: 10.1136/bjophthalmol-2013-304453. Epub 2014 Apr 2.
PubMed 24695688Heikal MA, Soliman TT, Abousaif WS, Shebl AA. A comparative study between ciclosporine A eye drop (2%) and tacrolimus eye ointment (0.03%) in management of children with refractory vernal keratoconjunctivitis. Graefes Arch Clin Exp Ophthalmol. 2022 Jan;260(1):353-361. doi: 10.1007/s00417-021-05356-0. Epub 2021 Aug 28.
PubMed 34453603
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Trial of 3% Diquafosol Ophthalmic Solution for Active Moderate-to-Severe Vernal Keratoconjunctivitis
- ClinicalTrials.gov ID
- NCT06903884
- Acronym / sponsor ID
- VKC001
- Conditions
- Vernal Keratoconjunctivitis
- Keywords
- Vernal Keratoconjunctivitis, Dry eye disease, Diquafosol, 0.1% Cyclosporin A
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 94 participants (estimated)
- Lead sponsor
- The University of Hong KongUniversity, hospital or other
- Study start
- 9 Feb 2026 (actual)
- Primary completion
- 30 Jun 2028 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 1 Apr 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- best corrected visual acuity,
- slit lamp biomicroscope examination,
- tear meniscus height and non-invasive keratographic tear breakup time(NIKBUT) measurement,
- cornea fluorescein staining (CFS) and
- 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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- One group of subjects will receive topical treatment with 3% Diquafosol ophthalmic solution and 0.1% Cyclosporin A cationic ophthalmic emulsion; another group of subjects will receive 0.1% Cyclosporin A cationic ophthalmic emulsion
| Arm | Type | Receives |
|---|---|---|
| 3% Diquafosol ophthalmic solution and 0.1% Cyclosporin A cationic ophthalmic emulsion | Experimental | Drug: 3% Diquafosol ophthalmic solution and 0.1% Cyclosporin A cationic ophthalmic emulsion3% Diquafosol eyedrops 6x/day + 0.1% Cyclosporin A twice a day |
| 0.1% Cyclosporin A cationic ophthalmic emulsion | Active comparator | Drug: 0.1% Cyclosporin A cationic ophthalmic emulsion0.1% Cyclosporin A eyedrops twice a day + preservative free sodium hyaluronate eyedrops 6x/day |
Who may qualify
- Ages
- 6 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 3% Diquafosol ophthalmic solution and 0.1% Cyclosporin A cationic ophthalmic emulsionThis arm is to investigate whether patients with moderate-to-severe VKC and keratitis will benefit from the addition of Diquafosol ophthalmic solution | Drug | 3% Diquafosol ophthalmic solution and 0.1% Cyclosporin A cationic ophthalmic emulsion |
| 0.1% Cyclosporin A cationic ophthalmic emulsionThis 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 | Drug | 0.1% Cyclosporin A cationic ophthalmic emulsion |
Primary outcome
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.
8 secondary outcomes
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
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
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
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
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
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
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
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2026.
- Background: PubMed 34731901Biermann J, Bosche F, Eter N, Beisse F. Treating Severe Pediatric Keratoconjunctivitis with Topical Cyclosporine A. Klin Monbl Augenheilkd. 2022 Nov;239(11):1374-1380. doi: 10.1055/a-1556-1182. Epub 2021 Nov 3. English, German.
- Background: PubMed 1800929Bleik JH, Tabbara KF. Topical cyclosporine in vernal keratoconjunctivitis. Ophthalmology. 1991 Nov;98(11):1679-84. doi: 10.1016/s0161-6420(91)32069-4.
- Background: PubMed 31770513Bremond-Gignac D, Doan S, Amrane M, Ismail D, Montero J, Nemeth J, Aragona P, Leonardi A; VEKTIS Study Group. Twelve-Month Results of Cyclosporine A Cationic Emulsion in a Randomized Study in Patients With Pediatric Vernal Keratoconjunctivitis. Am J Ophthalmol. 2020 Apr;212:116-126. doi: 10.1016/j.ajo.2019.11.020. Epub 2019 Nov 23.
- Background: PubMed 25818961Coban-Karatas M, Ozkale Y, Altan-Yaycioglu R, Sizmaz S, Pelit A, Metindogan S, Canturk-Ugurbas S, Aydin-Akova Y. Efficacy of topical 0.05% cyclosporine treatment in children with severe vernal keratoconjunctivitis. Turk J Pediatr. 2014 Jul-Aug;56(4):410-7.
- Background: PubMed 22001151De Smedt S, Nkurikiye J, Fonteyne Y, Tuft S, De Bacquer D, Gilbert C, Kestelyn P. Topical ciclosporin in the treatment of vernal keratoconjunctivitis in Rwanda, Central Africa: a prospective, randomised, double-masked, controlled clinical trial. Br J Ophthalmol. 2012 Mar;96(3):323-8. doi: 10.1136/bjophthalmol-2011-300415. Epub 2011 Oct 14.
- Background: PubMed 11318292Gupta V, Sahu PK. Topical cyclosporin A in the management of vernal keratoconjunctivitis. Eye (Lond). 2001 Feb;15(Pt 1):39-41. doi: 10.1038/eye.2001.10.
- Background: PubMed 24979519Keklikci U, Dursun B, Cingu AK. Topical cyclosporine a 0.05% eyedrops in the treatment of vernal keratoconjunctivitis - randomized placebo-controlled trial. Adv Clin Exp Med. 2014 May-Jun;23(3):455-61. doi: 10.17219/acem/37145.
- Background: PubMed 23156846Labcharoenwongs P, Jirapongsananuruk O, Visitsunthorn N, Kosrirukvongs P, Saengin P, Vichyanond P. A double-masked comparison of 0.1% tacrolimus ointment and 2% cyclosporine eye drops in the treatment of vernal keratoconjunctivitis in children. Asian Pac J Allergy Immunol. 2012 Sep;30(3):177-84.
- Background: PubMed 26957853Al-Amri AM, Mirza AG, Al-Hakami AM. Tacrolimus Ointment for Treatment of Vernal Keratoconjunctivitis. Middle East Afr J Ophthalmol. 2016 Jan-Mar;23(1):135-8. doi: 10.4103/0974-9233.164616.
- Background: PubMed 29118487Al-Amri AM, Fiorentini SF, Albarry MA, Bamahfouz AY. Long-term use of 0.003% tacrolimus suspension for treatment of vernal keratoconjunctivitis. Oman J Ophthalmol. 2017 Sep-Dec;10(3):145-149. doi: 10.4103/ojo.OJO_232_2014.
- Background: PubMed 34029239Caputo R, Marziali E, de Libero C, Di Grande L, Danti G, Virgili G, Villani E, Mori F, Bacci GM, Lucenteforte E, Pucci N. Long-Term Safety and Efficacy of Tacrolimus 0.1% in Severe Pediatric Vernal Keratoconjunctivitis. Cornea. 2021 Nov 1;40(11):1395-1401. doi: 10.1097/ICO.0000000000002751.
- Background: PubMed 27310883Chatterjee S, Agrawal D. Tacrolimus in Corticosteroid-Refractory Vernal Keratoconjunctivitis. Cornea. 2016 Nov;35(11):1444-1448. doi: 10.1097/ICO.0000000000000918.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Kendrick Co Shih principal investigator
The University of Hong Kong, Grantham Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing 3% Diquafosol ophthalmic solution and 0.1% Cyclosporin A cationic ophthalmic emulsion and 0.1% Cyclosporin A cationic ophthalmic emulsion in people with Vernal Keratoconjunctivitis, run by The University of Hong Kong at 1 site in Hong Kong.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 30 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Hong Kong. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kendrick Co Shih (39621412, kcshih@hku.hk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06903884, which also lists 39 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Apr 2026.