A Study to Compare the Effectiveness and Safety of T1695 (0.1% Tacrolimus) Versus Ciclosporin in Participants With Moderate to Severe Vernal Keratoconjunctivitis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Laboratoires Thea

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Decision date (initial)

2025-11-10

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Laboratoires THEA

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To compare the efficacy of T1695 0.1% ophthalmic suspension twice a day (BID) versus Ciclosporin 0.1% ophthalmic emulsion four times a day (QID) at D29 on the evolution of keratitis in participants with moderate to severe VKC.

Secondary objectives 6

1. 1. To compare the efficacy of T1695 0.1% ophthalmic suspension BID versus Ciclosporin 0.1% ophthalmic emulsion QID at D29 on the evolution of symptoms in participants with moderate to severe VKC.
2. 2. To evaluate the efficacy of T1695 0.1% ophthalmic suspension BID versus Ciclosporin 0.1% ophthalmic emulsion QID on the evolution of all assessments over the 3-month treatment period (Period 1) in participants with moderate to severe VKC.
3. 3. To evaluate the efficacy of T1695 0.1% ophthalmic suspension BID versus Ciclosporin 0.1% ophthalmic emulsion QID in the follow-up period (Period 2) on the evolution of all assessments in responder participants at D85.
4. 4. To evaluate the recurrence of active VKC in T1695 0.1% ophthalmic suspension BID versus Ciclosporin 0.1% ophthalmic emulsion QID in the follow-up period (Period 2) in responder participants at D85.
5. 5. To evaluate the safety and tolerability of T1695 0.1% ophthalmic suspension BID versus Ciclosporin 0.1% ophthalmic emulsion QID in moderate to severe VKC per period (for Period 2, only in responder participants at D85).
6. 6. To evaluate the safety and tolerability of T1695 0.1% ophthalmic suspension BID versus Ciclosporin 0.1% ophthalmic emulsion QID in moderate to severe VKC in the follow-up period (Period 2) in non-responder participants at D85.

Conditions and MedDRA coding

Vernal Keratoconjunctivitis (VKC)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-003625-PIP01-24

Plan to share IPD

No

IPD plan description

NA

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. 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
2. At the Screening visit: 2. Male or female participant from 4 years to less than 18 years old.
3. 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
4. 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.
5. 5. Participant requiring therapy for moderate to severe VKC and for whom there is no contraindication to treatment with ciclosporin and tacrolimus.
6. 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.
7. 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.
8. At the Randomisation visit: 8. Grading score of 3 or 4 on the Bonini scale for clinical grading of VKC in each eye.
9. 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.
10. 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.
11. At the Randomisation visit: 11. Participant with a Quality of Life in children with VKC (16-48 QUICK) questionnaire score from 32 to 48.

Exclusion criteria 21

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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).
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. 4. Exclusion criteria related to general conditions 4.1. History of drug or psychotropic substances consumption; drug or psychotropic substances abuse or any addiction.
15. 4. Exclusion criteria related to general conditions 4.2. History of drug addiction or alcohol abuse according to the Investigator’s judgement.
16. 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.
17. 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).
18. 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).
19. 4. Exclusion criteria related to general conditions 4.6. Participation in this study at the same time as another clinical study.
20. 4. Exclusion criteria related to general conditions 4.7. Participant previously randomised in this study.
21. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 24

1. 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
2. 2. Change from baseline (D1) at D29 (W4) in CFS grade assessed by the (0-5) modified Oxford scale in the contralateral eye.
3. 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.
4. 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.
5. 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).
6. 6. Presence of corneal ulcer at each post-baseline visit in the study eye and contralateral eye.
7. 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)).
8. 8. IMP Responder status (as defined in section Study design) (Y/N) at each post-baseline visit.
9. 9. First post-baseline visit (day) with IMP response.
10. 10. Efficacy assessed by the investigator at each post-baseline visit.
11. 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.
12. 12. Presence of corneal ulcer at each visit in the study eye and contralateral eye.
13. 13. Use of rescue medication (Y/N) at each visit in the study eye and contralateral eye.
14. 14. Presence of recurrence (Y/N) (as defined in section Study design) of active VKC at any time post-D85.
15. 15. Time to recurrence (in days).
16. 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.
17. 17. Change from baseline (D1) and from D85 at each post-baseline visit separately for study eye and contralateral eye in: • The Far Best Corrected Visual Acuity expressed in LogMAR. • Each ocular sign scores."
18. 18. Ocular tolerance of the eye drop assessed by the investigator at each post-baseline visit.
19. 19. Ocular tolerance of the eye drop assessed by the participant (or relatives) at each post-baseline visit.
20. 20. Change from baseline (D1) and from D85 in Intraocular Pressure (IOP) separately for study eye and contralateral eye at each post-baseline visit.
21. 21. Change from baseline (D1) and from D85 in Vital signs at each post-baseline visit.
22. 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).
23. 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).
24. 24. AE and SAE (Serious Adverse Event) by SOC and PT.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Laboratoires Thea

Sponsor organisation

Laboratoires Thea

Address

Zone Industrielle Du Brezet, 12 Rue Louis Bleriot 12 Rue Louis Bleriot

City

Clermont Ferrand

Postcode

63100

Country

France

Scientific contact point

Organisation

Laboratoires Thea

Contact name

Corentin Le Camus

Public contact point

Organisation

Laboratoires Thea

Contact name

Corentin Le Camus

Third parties 4

Locations

5 EU/EEA countries · 18 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 130 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications