TACROLIMUS MONOHYDRATE for Vernal Keratoconjunctivitis (VKC)

Inclusion criteria

• {"criterion_text":"- 1. Informed consent signed and dated*. *Obtained from the participant (if the participant is able to understand and sign it) and his/her legally acceptable relatives (mother and/or father, or tutor or witness) according to regional laws and regulations prior to the initiation of any procedure"}
• {"criterion_text":"- At the Randomisation visit: 10. Visual Analog Scales (0-100mm VAS) of VKC symptoms (among photophobia, tearing, itching, and mucous discharge) of ≥60 mm in each eye."}
• {"criterion_text":"- At the Randomisation visit: 11. Participant with a Quality of Life in children with VKC (16-48 QUICK) questionnaire score from 32 to 48."}
• {"criterion_text":"- At the Screening visit: 2. Male or female participant from 4 years to less than 18 years old."}
• {"criterion_text":"- At the Screening visit: 3. Participant with grading score of 3 or 4 on the Bonini scale for clinical grading of VKC in each eye. or Participant with documented moderate to severe active VKC in each eye"}
• {"criterion_text":"- 4. Participant who experienced at least 1 relapse of active VKC in the past year prior to enrolment. and/or who is currently: a. Refractory to anti-allergic agents or b. Cortico-dependent or c. Resistant or insufficiently responsive to ophthalmic ciclosporin."}
• {"criterion_text":"- 5. Participant requiring therapy for moderate to severe VKC and for whom there is no contraindication to treatment with ciclosporin and tacrolimus."}
• {"criterion_text":"- 6. Participant able to safely discontinue the use of VKC medication (if any) for the specified wash-out period, according to the investigator’s judgment, or, if unable, participants are allowed to switch to a VKC treatment associated with a shorter washout period among the list of washout treatments shown in Table 1."}
• {"criterion_text":"- 7. Participant able to be enrolled early during the VKC season in order to allow the 3-month treatment Period 1 during the VKC season."}
• {"criterion_text":"- At the Randomisation visit: 8. Grading score of 3 or 4 on the Bonini scale for clinical grading of VKC in each eye."}
• {"criterion_text":"- At the Randomisation visit: 9. Severe keratitis defined as 4 or 5 on the (0-5) modified Oxford corneal fluorescein staining score in each eye."}

Exclusion criteria

• {"criterion_text":"- 1. Ophthalmic exclusion criteria in ANY EYES Participant having experienced or experiencing at screening or randomisation visit: 1.1 Naïve participant (participant who did not receive any VKC treatment prior to enrolment) with moderate VKC defined as < 3 on the Bonini scale for clinical grading of VKC."}
• {"criterion_text":"- 2. Systemic/Non-ophthalmic exclusion criteria Participant having experienced or experiencing at Screening or Randomisation: 2.5 Participants with untreated asthma judged as severe by the investigator based on participant’s medical history."}
• {"criterion_text":"- 2. Systemic/Non-ophthalmic exclusion criteria Participant having experienced or experiencing at Screening or Randomisation: 2.6 History of malignancy within the last 5 years."}
• {"criterion_text":"- 3. Specific exclusion criteria regarding childbearing potential women 3.1 Pregnancy for post menarche participant (confirmed with a positive urine pregnancy test) and nursing mothers."}
• {"criterion_text":"- 3. Specific exclusion criteria regarding childbearing potential women 3.2 Male/female of childbearing potential who is sexually active and is not willing to use preventive measures."}
• {"criterion_text":"- 4. Exclusion criteria related to general conditions 4.1. History of drug or psychotropic substances consumption; drug or psychotropic substances abuse or any addiction."}
• {"criterion_text":"- 4. Exclusion criteria related to general conditions 4.2. History of drug addiction or alcohol abuse according to the Investigator’s judgement."}
• {"criterion_text":"- 4. Exclusion criteria related to general conditions 4.3. Inability of participant and/or relatives to understand the study procedures or to give informed consent."}
• {"criterion_text":"- 4. Exclusion criteria related to general conditions 4.4. Non-compliant participant and/or relatives (e.g., not willing to attend a visit or completing the self-questionnaire)."}
• {"criterion_text":"- 4. Exclusion criteria related to general conditions 4.5. Participation in this study within the 4 weeks after the end of a previous clinical study (or within 5 half-lives of the previously tested product if longer than 4 weeks)."}
• {"criterion_text":"- 4. Exclusion criteria related to general conditions 4.6. Participation in this study at the same time as another clinical study."}
• {"criterion_text":"- 1. Ophthalmic exclusion criteria in ANY EYES Participant having experienced or experiencing at screening or randomisation visit: 1.2. Any type of ocular surgery, including eye lid interventions within 6 months before the randomisation visit."}
• {"criterion_text":"- 4. Exclusion criteria related to general conditions 4.7. Participant previously randomised in this study."}
• {"criterion_text":"- 5. Exclusion criteria related to previous and concomitant treatments (medications/non-medicinal therapies/procedures) Participant with previous, current or anticipated prohibited listed treatment (or prohibited modification of treatment regimen). The prohibited treatments (or prohibited modifications of treatment regimen) and their periods of use prohibition are listed in the protocol_ Table 1. Prohibited treatments"}
• {"criterion_text":"- 1. Ophthalmic exclusion criteria in ANY EYES Participant having experienced or experiencing 1.3. Any pre-existing eye condition (other than VKC) that could affect assessment or interpretation of study endpoints, such as trauma, severe blepharitis, keratitis, corneal ulcer, glaucoma, uveitis, or active ocular infection, etc."}
• {"criterion_text":"- 1. Ophthalmic exclusion criteria in ANY EYES Participant having experienced or experiencing at screening or randomisation visit: 1.4. History of Herpes Simplex Keratitis varicella-zoster."}
• {"criterion_text":"- 1. Ophthalmic exclusion criteria in ANY EYES Participant having experienced or experiencing at screening or randomisation visit: 1.5. Any ocular diseases other than VKC that would require topical ocular treatment during the study."}
• {"criterion_text":"- 2. Systemic/Non-ophthalmic exclusion criteria Participant having experienced or experiencing at Screening or Randomisation: 2.1 Known or suspected hypersensitivity to one of the components of the Investigational Medicinal Product(s) or auxiliary treatments (e.g. rescue medication) or diagnostic agents used during the study (e.g., potential topical anaesthetic, fluorescein)."}
• {"criterion_text":"- 2. Systemic/Non-ophthalmic exclusion criteria Participant having experienced or experiencing at Screening or Randomisation: 2.2 History of, or active relevant systemic condition incompatible with the study or likely to interfere with the study results or the participant safety according to investigator judgment."}
• {"criterion_text":"- 2. Systemic/Non-ophthalmic exclusion criteria Participant having experienced or experiencing at Screening or Randomisation: 2.3 Disease not stabilised within 30 days before the screening visit (e.g. diabetes with outof- range glycemia, thyroid malfunction, uncontrolled autoimmune disease, current systemic infection), or judged by the investigator to be incompatible with the study."}
• {"criterion_text":"- 2. Systemic/Non-ophthalmic exclusion criteria Participant having experienced or experiencing at Screening or Randomisation: 2.4 Presence or history of systemic allergy (e.g., allergic rhinitis, food allergy) judged as severe by the investigator."}

Primary endpoints

• {"endpoint_text":"- Change from baseline (D1) at D29 (W4) in Corneal Fluorescein Staining (CFS) grade assessed by the (0-5) modified Oxford scale in the study eye.","definition_or_measurement_approach":"Change from baseline at Day 29 measured by Corneal Fluorescein Staining (CFS) grade using the (0-5) modified Oxford corneal fluorescein staining scale in the study eye."}

Secondary endpoints

• {"endpoint_text":"- 1. Change from baseline (D1) at D29 (W4) in the 0 to 100mmVisual Analog Scales (VAS) value among 4 symptoms associated with VKC: photophobia, tearing, itching and mucous discharge in the study eye and contralateral eye","definition_or_measurement_approach":"Change from baseline at D29 on 0-100 mm VAS for specified VKC symptoms (photophobia, tearing, itching, mucous discharge) measured in both study and contralateral eye."}
• {"endpoint_text":"- 2. Change from baseline (D1) at D29 (W4) in CFS grade assessed by the (0-5) modified Oxford scale in the contralateral eye.","definition_or_measurement_approach":"Change from baseline at D29 in CFS grade using the (0-5) modified Oxford scale in the contralateral eye."}
• {"endpoint_text":"- 3. Change from baseline (D1) at each post-baseline visit in CFS grade assessed by the (0-5) modified Oxford scale the study eye and contralateral eye.","definition_or_measurement_approach":"Change from baseline at each post-baseline visit in CFS grade by (0-5) modified Oxford scale in both eyes."}
• {"endpoint_text":"- 4. Change from baseline (D1) at each post-baseline assessment in the 0-100mm VAS value among 4 symptoms associated with VKC: photophobia, tearing, itching and mucous discharge in the study eye and contralateral eye.","definition_or_measurement_approach":"Change from baseline at each post-baseline assessment in 0-100 mm VAS for 4 VKC symptoms in both eyes."}
• {"endpoint_text":"- 5. Change from baseline (D1) at each post-baseline visit in the study eye and/or contralateral eye in: • VKC severity (Bonini scale 0–5) • Bulbar hyperaemia • Trantas dots • Tarsal papillae (all via slit lamp) • Corneal/limbal staining (VKC-CLEK scale).","definition_or_measurement_approach":"Change from baseline in clinical signs assessed by slit lamp and scales: Bonini VKC severity (0–5), bulbar hyperaemia, Trantas dots, tarsal papillae, and corneal/limbal staining by VKC-CLEK."}
• {"endpoint_text":"- 6. Presence of corneal ulcer at each post-baseline visit in the study eye and contralateral eye.","definition_or_measurement_approach":"Presence/absence of corneal ulcer recorded at each post-baseline visit for both study and contralateral eye."}
• {"endpoint_text":"- 7. Change from baseline (D1) at each post-baseline visit in the Quality of Life (QoL) Questionnaire scores (QUICK questionnaire (score 16-48) and Impact on ability to attend school (score1-3)).","definition_or_measurement_approach":"Change from baseline in QoL measures: QUICK questionnaire (16-48) and school attendance impact score (1-3) at each post-baseline visit."}
• {"endpoint_text":"- 8. IMP Responder status (as defined in section Study design) (Y/N) at each post-baseline visit.","definition_or_measurement_approach":"Responder status (Yes/No) per IMP-defined criteria assessed at each post-baseline visit (definition located in Study design section of protocol)."}
• {"endpoint_text":"- 9. First post-baseline visit (day) with IMP response.","definition_or_measurement_approach":"Timepoint (day) of first post-baseline visit at which IMP response is observed."}
• {"endpoint_text":"- 10. Efficacy assessed by the investigator at each post-baseline visit.","definition_or_measurement_approach":"Investigator global assessment of efficacy at each post-baseline visit."}
• {"endpoint_text":"- 11. Change from baseline (D1) and from D85 at each visit in the study eye and contralateral eye in: • CFS (Oxford scale 0–5) • The 0–100 mm VAS for VKC among symptoms associate (photophobia, tearing, itching, discharge) • Clinical grading of VKC - severity (Bonini scale 0–5) • Bulbar conjunctiva hyperaemia, Limbus Trantas dot, or tarsal conjunctival papillae assessed by slit lamp examination.","definition_or_measurement_approach":"Change from baseline and from Day 85 for listed ocular assessments (CFS Oxford 0–5, symptom VAS 0–100, Bonini severity 0–5, bulbar hyperaemia, Trantas dots, tarsal papillae) assessed by slit-lamp."}
• {"endpoint_text":"- 12. Presence of corneal ulcer at each visit in the study eye and contralateral eye.","definition_or_measurement_approach":"Presence/absence of corneal ulcer at each visit in both eyes."}
• {"endpoint_text":"- 13. Use of rescue medication (Y/N) at each visit in the study eye and contralateral eye.","definition_or_measurement_approach":"Recording of rescue medication use (Yes/No) at each visit for study and contralateral eye."}
• {"endpoint_text":"- 14. Presence of recurrence (Y/N) (as defined in section Study design) of active VKC at any time post-D85.","definition_or_measurement_approach":"Recurrence (Yes/No) of active VKC post-Day 85 per protocol definition."}
• {"endpoint_text":"- 15. Time to recurrence (in days).","definition_or_measurement_approach":"Time (days) from reference point to recurrence event."}
• {"endpoint_text":"- 16. Ocular and systemic treatment-emergent adverse event (TEAE) and related TEAE by System Organ Class (SOC) and Preferred Term (PT), TEAE leading to study treatment discontinuation, Serious TEAE.","definition_or_measurement_approach":"Safety reporting: ocular and systemic TEAEs coded by SOC and PT, TEAEs leading to discontinuation, and serious TEAEs."}
• {"endpoint_text":"- 17. Change from baseline (D1) and from D85 at each post-baseline visit separately for study eye and contralateral eye in: •\tThe Far Best Corrected Visual Acuity expressed in LogMAR. •\tEach ocular sign scores.\"","definition_or_measurement_approach":"Change in BCVA (LogMAR) and individual ocular sign scores from baseline and from Day 85 at each visit for each eye."}
• {"endpoint_text":"- 18. Ocular tolerance of the eye drop assessed by the investigator at each post-baseline visit.","definition_or_measurement_approach":"Investigator-assessed ocular tolerance of study eye drops at each visit."}
• {"endpoint_text":"- 19. Ocular tolerance of the eye drop assessed by the participant (or relatives) at each post-baseline visit.","definition_or_measurement_approach":"Participant/relative-reported ocular tolerance assessments at each post-baseline visit."}
• {"endpoint_text":"- 20. Change from baseline (D1) and from D85 in Intraocular Pressure (IOP) separately for study eye and contralateral eye at each post-baseline visit.","definition_or_measurement_approach":"IOP measurements for each eye with change from baseline and from Day 85 recorded at each post-baseline visit."}
• {"endpoint_text":"- 21. Change from baseline (D1) and from D85 in Vital signs at each post-baseline visit.","definition_or_measurement_approach":"Change from baseline and from Day 85 in vital signs at each post-baseline visit."}
• {"endpoint_text":"- 22. Blood concentration of tacrolimus (ng/mL) at the baseline visit (D1, before IMP instillation) and at D29 (between 1h and 3h post IMP instillation) (Period 1).","definition_or_measurement_approach":"Tacrolimus blood concentration (ng/mL) at baseline (pre-instillation) and at Day 29 between 1 and 3 hours post-instillation (Period 1)."}
• {"endpoint_text":"- 23. Change from baseline (D1) in complete blood count (CBC), basic metabolic panels, kidney and liver tests at the baseline visit (D1, before IMP instillation) and at D85 (Period 1).","definition_or_measurement_approach":"Laboratory safety parameters (CBC, basic metabolic panel, renal and hepatic tests) change from baseline at D85."}
• {"endpoint_text":"- 24. AE and SAE (Serious Adverse Event) by SOC and PT.","definition_or_measurement_approach":"Adverse events and serious adverse events coded by System Organ Class and Preferred Term."}

Methods

• Doctor-to-doctor letters (K2_Recruitment material__dr_to_dr_letter) — clinician-targeted recruitment materials present (country-specific versions exist).
• Posters with flyer (K2_Recruitment material__poster_with_flyer_Redacted) — site/community poster materials (country-specific versions exist).
• Caregiver brochure / caregiver materials (K2_Recruitment material_Caregiver brochure) — informational brochure for caregivers/parents (country-specific versions exist).
• Website recruitment language / online recruitment content (K2_Recruitment material__ Website Language_Redacted / Website Language File) — web-based recruitment materials (country-specific versions exist).
• Patient-facing printed materials and local GP/paediatrician letters (L2_Other subject information material_Pediatricion GP letter, GP Letter) — outreach via primary care and paediatric clinicians.

Bulgaria

Earliest CTIS Part Ii Submission Date

22-10-2025

Latest Decision Or Authorization Date

05-02-2026

Processing Time Days

107

Number Of Sites

3

Number Of Participants

12

France

Earliest CTIS Part Ii Submission Date

16-10-2025

Latest Decision Or Authorization Date

06-02-2026

Processing Time Days

113

Number Of Sites

3

Number Of Participants

12

Greece

Earliest CTIS Part Ii Submission Date

23-10-2025

Latest Decision Or Authorization Date

09-02-2026

Processing Time Days

109

Number Of Sites

4

Number Of Participants

16

Italy

Earliest CTIS Part Ii Submission Date

16-10-2025

Latest Decision Or Authorization Date

06-02-2026

Processing Time Days

114

Number Of Sites

5

Number Of Participants

20

Spain

Earliest CTIS Part Ii Submission Date

01-08-2025

Latest Decision Or Authorization Date

05-02-2026

Processing Time Days

189

Number Of Sites

3

Number Of Participants

12

Primary sponsor

Full Name

Laboratoires Thea

Organisation Type

Pharmaceutical company

Country Of Registered Address

France

Contract research organisations

Name

Syneos Health Hellas Single Member S.A.

Responsibilities

Study startup and related study operational support (sponsor duties codes include 1 and 15)

Name

Syneos Health France S.A.R.L.

Responsibilities

Study startup, EC and RA applications and patient reimbursement, regulatory and operational support (multiple sponsor duties listed)

Third parties

• {"country":"United States","full_name":"Veeva Systems Inc.","duties_or_roles":"RTSM – Randomization and Trial Supply Management; sponsor duties codes include code 15 and code 3 (RTSM vendor)","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Greece","full_name":"Syneos Health Hellas Single Member S.A.","duties_or_roles":"Study startup and other startup activities (sponsor duties codes include 1 and 15; contact SM_SSU_GREECE@syneoshealth.com)","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Syneos Health France S.A.R.L.","duties_or_roles":"Study startup, EC and RA applications and patient reimbursement, and other operational tasks (multiple sponsor duties: study startup, EC and RA applications and patient reimbursement, regulatory and operational roles; contact Kathrin.vogel@syneoshealth.com)","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Acm Global Central Laboratory Limited","duties_or_roles":"Central laboratory services (kits, safety testing, project management, data management, courier management, specimen storage) and Bioanalytical (PK) testing; sponsor duties codes include 15 and 4","organisation_type":"Laboratory/Research/Testing facility"}