A study to evaluate safety and efficacy of two different doses of Isocyclosporin A eye drop solution in patients with Atopic Keratoconjunctivitis (AKC).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Dompe' Farmaceutici S.p.A.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Trial duration

10 May 2024 → 29 Nov 2024

Decision date (initial)

2024-03-27

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Dompé farmaceutici S.p.a.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Dose response, Efficacy, Safety

To evaluate the efficacy of IsoCsA BID and QID versus vehicle to demonstrate superiority of at least one of the two different dosages over the vehicle in the improvement of ocular itching in adult patients with AKC.

Secondary objectives 10

1. To evaluate the efficacy of each of the two dosages of IsoCsA ophthalmic solution in improving symptoms of atopic keratoconjunctivitis including itching, tearing, discomfort, mucous discharge, and photophobia as compared to vehicle.
2. To evaluate the efficacy of each of the two dosages of IsoCsA ophthalmic solution in improving signs of atopic keratoconjunctivitis including bulbar conjunctival hyperemia, upper and/or lower tarsal conjunctival papillae, punctate keratitis, corneal neovascularization, cicatrizing conjunctivitis, and blepharitis as compared to vehicle.
3. To evaluate the efficacy of each of the two dosages of IsoCsA ophthalmic solution in improving Quality of Life (QoL) as compared to vehicle.
4. To evaluate the efficacy of each of the two dosages of IsoCsA ophthalmic solution in improving signs and symptoms of atopic keratoconjunctivitis
5. To evaluate post-instillation tolerability of each of the two dosages of IsoCsA ophthalmic solution.
6. To evaluate the efficacy of each of the two dosages of IsoCsA ophthalmic solution in improving bulbar conjunctival redness as compared to vehicle.
7. To evaluate the efficacy of each of the two dosages of IsoCsA ophthalmic solution in improving corneal epithelial staining as compared to vehicle.
8. To evaluate the safety of each of the two dosages of Isocyclosporin A ophthalmic solution
9. To evaluate the tolerability of each of the two dosages of Isocyclosporin A ophthalmic solution
10. To assess blood concentration of CsA and IsoCsA after topical instillation of the two dosages of Isocyclosporin A ophthalmic solution

Conditions and MedDRA coding

Atopic keratoconjunctivitis (AKC)

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 1. Male or female patients aged ≥18 years.
2. 2. Diagnosis of AKC in both eyes, with an ocular itching VAS score≥ 50 AND at least one of the following clinical characteristics in at least one eye: a. Presence of upper and/or lower tarsal conjunctival papillary reaction and/or limbal papillary reaction. b. A composite symptom score (CSyS) ≥4 (sum of the severity scores graded 0 to 3 for each of the following: itching, tearing, ocular discomfort, photophobia, and mucous discharge scored (composite symptom score range 0 to 15). c. Grade≥ 2 of superficial punctate keratitis as evaluated by corneal fluorescein staining modified Oxford scale (a seven-point ordinal scale [0, 0.5, 1, 2, 3, 4 and 5] with zero corresponding to complete clearing of the cornea). d. Bulbar conjunctival hyperemia score ≥ 1 on a 4-points scale (0-3)
3. 3. Best corrected distance visual acuity score of +1.0 logMAR or better in both eyes at the time of study enrollment
4. 4. If a female of childbearing potential, has a negative pregnancy test at both screening and baseline visit.
5. 5. Only patients who satisfied all informed consent requirements will be included in the study; the patient and/or his/her legal representative must have read, signed, and dated the informed consent document before any study-related procedures were performed; the informed consent form signed by patients and/or legal representatives must have been approved by the IEC for the current study.
6. 6. Has the ability and willingness to comply with study procedures.
7. 7. For patients with concomitant dermatologic allergic manifestations, stable doses of topical calcineurin inhibitors (e.g., topical tacrolimus or topical pimecrolimus) for dermatological use, including periocular and eyelid skin, are allowed if on stable doses for 30 days prior to Baseline (Day 1) and anticipated to stay on pre-study stable doses for the entire study period. However, they are not allowed on the ocular surface.
8. 8. Systemic immunomodulatory treatments for atopic dermatitis are allowed only if on stable doses for 30 days prior to Baseline (Day 1) and anticipated to stay on pre-study stable doses for the entire study period.
9. 9. For patients with concomitant ocular conditions other than AKC that require topical ophthalmic medications, they may be included if the medications are not topical ophthalmic antiallergic, corticosteroids or calcineurin inhibitors and the patients have been on a stable dose for at least the past 3 months, which is anticipated to remain the same for the entire duration for the entire study period.

Exclusion criteria 19

1. 1. Inability to speak and understand the local language sufficiently to understand the nature of the study, to provide written informed consent, and to allow the completion of all study assessments.
2. 2. Evidence of an active ocular infection in either eye
3. 3. Intraocular inflammation defined as Tyndall score >0 in either eye.
4. 4. Known or suspected ocular malignancy (ocular surface, intraocular, ocular adnexa)
5. 5. Presence of cancer or any other systemic disease that may affect the ability to participate in the clinical study in the opinion of the investigator including basal cell carcinoma.
6. 6. Patients that are anatomically monocular.
7. 7. Systemic disease not stabilized within 1 month before the screening visit (e.g., diabetes with glycemia out of range, thyroid malfunction) or judged by the investigator to be incompatible with the study (e.g., current systemic infections) or with a condition incompatible with the frequent assessment required by the study.
8. 8. Received systemic administration of corticosteroids or immunosuppressive in the past 30 days prior to Screening visit.
9. 9. History of a serious adverse reaction or significant hypersensitivity to any drug or chemically related compounds to the Study Product or a clinically significant allergy to drugs, foods, amide local anesthetics or other materials and drugs used in this study.
10. 10. Females of childbearing potential (i.e., not surgically sterilized or postmenopausal for at least 1 year) are excluded from participation in the study if they meet any one of the following conditions: a. Are pregnant, b. Have a positive result at the urine pregnancy test (screening/baseline Day 1) c. Intend to become pregnant during the study treatment period, d. Are breastfeeding, e. Unwilling to continue to use highly effective birth control measures such as hormonal contraceptives (oral, implanted, transdermal, or injected), sexual abstinence (defined as refraining from heterosexual intercourse as usual and customary lifestyle) during the entire course of and 30 days after the study treatment period.
11. 11. Male fertile patients (i.e. not surgically sterilized by vasectomy) unwilling to use an acceptable form of contraception (male condom with spermicidal cream or jelly).
12. 12. Any concurrent medical condition that, in the judgment of the principal investigator, might interfere with the conduct of the study, confound the interpretation of the study results, or endanger the patient’s well-being.
13. 13. Use of topical ophthalmic cyclosporin A or other calcineurin inhibitors such as tacrolimus, pimecrolimus and topical ophthalmic corticosteroids in either eye in the past 2 weeks.
14. 14. Contact lenses or punctum plug use during the study (previous use is not an exclusion criterion but must be discontinued at the Screening Visit/ Visit 1).
15. 15. Diagnosis of other systemic diseases that are associated with ocular inflammation such as Sjogren’s disease, rheumatological diseases such as rheumatoid arthritis
16. 16. History of drug addiction or alcohol abuse (>1 drink /day for women and >2 drinks /day for men following USDA dietary Guidelines 2020-2025).
17. 17. Any prior ocular surgery (including cryosurgery or surgical excision of giant papillae) within 60 days before the screening visit in either eye.
18. 18. Participation in a clinical trial with a new active substance, including medical devices in the past 60 days.
19. 19. Participation in another clinical trial study at the same time as the present study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Mean change from baseline to Week 4 in ocular itching score assessed by visual analogue scale (VAS) [Time Frame: week 4].

Secondary endpoints 11

1. Mean change from baseline in ocular symptoms (itching, tearing, discomfort, mucous discharge, photophobia) composite score (0-15) [Time Frame: week 4, 6].
2. Mean change from baseline in: - ocular itching evaluated on a 4-point scale(0-3)[Time Frame (TF): week 4, 6] - ocular tearing evaluated on a 4-point scale(0-3)[TF: week 4, 6] - ocular discomfort evaluated on a 4-point scale(0-3)[TF: week 4, 6] - ocular mucous discharge evaluated on a 4-point scale(0-3)[TF: week 4, 6] - photophobia evaluated on a 4-point scale(0-3)[TF: week 4, 6] - ocular itching score assessed by visual analog scale(VAS) [TF: week 2, 6]
3. Mean change from baseline in ocular signs (Bulbar conjunctival hyperemia, upper tarsal conjunctival papillae, punctate keratitis, corneal neovascularization, cicatrizing conjunctivitis, and blepharitis) composite score [Time Frame: week 4,6]. Mean change from baseline in blepharitis evaluated on a 4-point scale (0-3) [Time Frame: week 4, 6]
4. Mean change from baseline of the Quality of Life (QoL) scores assessed by the Standardized Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ-S) Time Frame: week 4].
5. Mean change from baseline in ocular symptoms and signs composite score (0-33) [Time Frame: week 4, 6].
6. Mean change of post-instillation comfort score (0-4) [Time Frame: at baseline and week 2].
7. Mean change from baseline in bulbar conjunctival hyperemia, evaluated on a 4-point scale (0-3) [Time Frame: week 2, 4, 6].
8. Mean change from baseline in corneal epithelial fluorescein staining (modified Oxford scale) [Time Frame: week 2, 4, 6].
9. Incidence and frequency of treatment-emergent adverse events (TEAEs) assessed throughout the study. Mean change from baseline in best corrected distance visual acuity (BCDVA) [Time Frame: at week 2, 4, 6]. Mean change from baseline in corneal endothelial cell density in both eyes (only at selected sites that have the required equipment) [Time Frame: at week 6] (for the other part please refer to protocol)
10. Treatment discontinuation rate due to tolerability [Time Frame: at week 4]
11. Descriptive pharmacokinetic (PK) assessment [Time Frame: baseline, at week 2, 4]

Investigational products

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

Test 1

Placebo 1

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Dompe' Farmaceutici S.p.A.

Sponsor organisation

Dompe' Farmaceutici S.p.A.

Address

Via Santa Lucia 6

City

Milan

Postcode

20122

Country

Italy

Scientific contact point

Organisation

Dompe' Farmaceutici S.p.A.

Contact name

Marta Sacchetti, Global Head of Clinical Development Ophthalmology & Neurotrophins

Public contact point

Organisation

Dompe' Farmaceutici S.p.A.

Contact name

Flavio Mantelli, MD, PhD Chief Medical Officer

Third parties 9

Locations

1 EU/EEA country · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 22 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