Safety, Tolerability, and Distribution of Topical Laquinimod Eye Drops : a Phase 1 Study

Study Overview
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Brief Summary
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The LION Study is a prospective, open-label, single-center phase 1 clinical trial to evaluate the safety, tolerability, and distribution of Laquinimod administered as topical eye drops for two weeks in human participants.

Detailed Description
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A total of up to 15 participants who fulfill the study eligibility criteria and who are planned to undergo a pars plana vitrectomy for selected indications i.e. macular hole or macular pucker/epiretinal membrane) will be enrolled in the study. Eligible participants scheduled for a diagnostic vitrectomy may also be enrolled. The study will consist of up to three subsequent dose-escalation groups and, following bioanalytical analyses, an optional expansion group at the maximum tolerated dose (MTD), at the highest dose under study, or in order to expand a previous dose group. Group 1 to 3 samples will be assayed for Laquinimod concentration in aqueous humor, vitreous and plasma.

Official Title
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Safety, Tolerability, and Distribution of Topical Laquinimod Eye Drops , an Innovative ImmunomodulatOr Targeting Aryl hydrocarboN Receptor (AhR): a Phase 1 Study - The LION Study

Conditions
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Uveitis

Intervention / Treatment
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* Drug: Laquinimod eye drops


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or older Participants who are capable and willing to provide informed consent and follow study instructions. Participants with epiretinal membrane or macular hole who are scheduled to undergo pars plana vitrectomy (PPV)OR Participants who are scheduled to undergo a diagnostic vitrectomy. Participants with intraocular pressure (IOP) ≥ 5 mmHg and ≤22 mmHg in study eye Women who are not pregnant or lactating, are post-menopausal or have undergone a sterilization procedure. Exclusion Criteria: Participants with active periocular or ocular infectious disease (e.g., blepharitis, scleritis, or conjunctivitis, keratitis or endophthalmitis). Participants with active infectious uveitis Participants with a history of prior intraocular or extraocular surgery within 90 days of study enrollment Participant with a history of intravitreal steroids administered to the study eye within 90 days of enrollment. Participants with a history of intravitreal injection of VEGF inhibitors within 30 days of enrollment Use of any topical cyclosporine or corticosteroid or other specified (i.e. calcineurin inhibitors) ophthalmic medication in the study eye for any reason within 14 days of enrollment and before the surgery Use of medication consisting of a strong or moderate inhibitor of CYP3A4 within 2 weeks of Baseline visit (and during the study). Use of medication consisting of a strong inducer of CYP3A4 within 2 weeks of Baseline visit (and during the study) Mild, moderate, or severe hepatic impairment (any of Child-Pugh Score A, B, and C) Moderate or severe renal impairment (GFR ≤60 mL/min) History of HIV disease or other immunodeficiency disorder History of acute hepatitis A (IgM positive), hepatitis B, or hepatitis C History of organ or bone marrow transplant Presence of malignancy under active treatment Any other acute or chronic medical condition that would, in the judgment of the study investigators, reasonably preclude participation in the clinical study Already enrolled in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: The study will consist of up to three subsequent dose-escalation groups and, following bioanalytical analyses, an optional group at the highest dose level under study or at the maximum tolerated dose (MTD).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>(3 to 6 participants): Participants will receive a dose of Laquinimod as 2 drops once a day (0.6mg per day) in the study eye for 14 days before the surgery. | Drug: Laquinimod eye drops<br>* n Laquinimod eye drops 10 mg/ml Dose: Dosing frequency will depend on the groups assigned<br>|
| Experimental: Group 2<br>(3 to 6 participants): Participants will receive a dose of Laquinimod as 2 drops twice a day (1.2mg per day) in the study eye for 14 days before the surgery | Drug: Laquinimod eye drops<br>* n Laquinimod eye drops 10 mg/ml Dose: Dosing frequency will depend on the groups assigned<br>|
| Experimental: Group 3<br>(3 to 6 participants): Participants will receive a dose of Laquinimod as 2 drops three times a day(1.8 mg per day) for 14 days before the surgery. | Drug: Laquinimod eye drops<br>* n Laquinimod eye drops 10 mg/ml Dose: Dosing frequency will depend on the groups assigned<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of Laquinimod in aqueous humor and vitreous samples of human participants | Assessment of concentration of Laquinimod in aqueous humor and vitreous samples of human by biolanalysis in specialized lab participants on Day 14 of Laquinimod eye-drop administration. | After 2 weeks of study drug administration | 
| Concentration of Laquinimod in plasma of human participants | Assessment of concentration of Laquinimod in plasma of human participants on Day 14 of Laquinimod in specialized lab eye-drop administration. participants on Day 14 of Laquinimod eye-drop administration. | After 2 weeks of study drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Assessment | Any Adverse events: ocular and non-ocular at POD 1 and POD 8 compared to baseline. | Baseline to end of Study at 22-30days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-anterior uveitis; Immunomodulation; Laquinimod; Topical