A Study of Laquinimod Eye-drops in Healthy Participants

Study Overview
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Brief Summary
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This is a Phase 1 randomized, double-masked, placebo-controlled study performed with healthy participants to assess the safety and tolerability of laquinimod eye-drops.

Detailed Description
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Laquinimod administered as an oral capsule formulation has previously been studied in neurodegenerative and autoimmune diseases. The clinical side effect profile of orally administered laquinimod is well-characterized based on this previous experience. This trial will establish a safe and tolerated dose of laquinimod when administered as an eye-drop formulation following single ascending dose (SAD) and multiple ascending dose (MAD) administrations. There are four planned groups in the SAD-part of the study which will enroll 28 participants, if all dose levels are explored. The subsequent MAD-part of the study will enroll another 28 participants.

Official Title
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A Placebo-Controlled, Double-masked Phase-1 Study in Healthy Subjects Investigating the Safety and Tolerability of Laquinimod Eye Drops

Conditions
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Eye Diseases

Intervention / Treatment
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* Drug: Laquinimod
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Main inclusion criteria: In good health according to medical history, physical examination, vital signs, ECG and clinical chemistry, urinary and hematological laboratory tests Main exclusion criteria: Unable or unwilling to use eye-drops Current usage of contact lenses History of eye surgery Sign or symptom of active eye disease History of an eye disease or other condition that could interfere with eye examinations in the study, or with ocular absorption of the investigational product History of inflammatory ocular disease History of cardiovascular or pulmonary disorder Family history of known or suspected hereditary cardiovascular disease Autoimmune disease or known family history of autoimmune disease Any other condition that would contraindicate subject's participation in the clinical study due to safety concerns or compliance with clinical study procedures

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Laquinimod - Single Ascending Doses<br>One single dose of laquinimod eye-drops. There are up to four planned dose levels. | Drug: Laquinimod<br>* Eye-drops<br>* Other names: ABR-215062;|
| Placebo Comparator: Placebo - Single Ascending Doses<br>One single dose of placebo eye-drops. | Drug: Placebo<br>* Eye-drops<br>|
| Experimental: Laquinimod - Multiple Ascending Doses<br>Eye-drops administered once daily for 14-21 days. There are up to two planned dose levels. The first dose level will be defined in the SAD-part of the study. | Drug: Laquinimod<br>* Eye-drops<br>* Other names: ABR-215062;|
| Placebo Comparator: Placebo - Multiple Ascending Doses<br>Eye-drops administered once daily for 14-21 days. | Drug: Placebo<br>* Eye-drops<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | Type, frequency, seriousness, severity and relationship to treatment | For 7 days post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participant-reported eye-toxicities | Assessed from change from baseline in ocular symptoms score determined using a Visual Analogue Scale with 0-100 range, where 0= no symptom and 100= worst possible discomfort. | Pre-dose (baseline) and immediately after the intervention | 
| Investigator-reported eye-toxicities - BCVA | Assessed from change from baseline in Best Corrected Visual Acuity (BCVA) using the Early Treatment Diabetic Retinopathy Study research group (ETDRS) visual acuity chart with objective and subjective refraction. | Pre-dose (baseline) and immediately after the intervention | 
| Investigator-reported eye-toxicities - Slit lamp examination | Assessed from change from baseline in slit lamp examination parameters (eyelid swelling, eyelid redness, conjunctival redness, conjunctival chemosis, scleral redness, corneal opacity, iris alterations and anterior chamber flare) graded on a 4-point scale where 0= none, 1= mild, 2= moderate, and 3= severe. | Pre-dose (baseline) and immediately after the intervention | 
| Investigator-reported eye-toxicities - Corneal fluorescein staining | Assessed from change from baseline in corneal fluorescein staining determined using the NEI/Industry Workshop guidelines. The cornea is divided into five sectors (central, superior, inferior, nasal and temporal) and each sector scored on a 4-point scale, where 0= no staining and 3= maximum staining. | At screening visit (baseline) and immediately after the intervention | 
| Investigator-reported eye-toxicities - Intraocular pressure | Assessed from change from baseline in intraocular pressure (mmHg) determined using a Goldmann applanation tonometer. | At screening visit (baseline) and immediately after the intervention | 
| Investigator-reported eye-toxicities - Funduscopy in mydriasis | Assessed from change from baseline in clinical signs detected by indirect funduscopic inspection of the optic disc, macula, retinal vessels and retinal periphery. | At screening visit (baseline) and immediately after the intervention | 
| Peak plasma concentration of laquinimod | Maximal plasma concentration (Cmax) of laquinimod as assessed from samples collected pre-dose and at frequent intervals over 7 days after (last) dose | Over up to 21 days after (last) dose | 
| Time to peak plasma concentration of laquinimod | Time to maximal plasma concentration (tmax) of laquinimod as assessed from samples collected pre-dose and at frequent intervals over 7 days after (last) dose | Over up to 21 days) after (last) dose | 
| Trough plasma concentration of laquinimod at steady-state | Minimal plasma concentration (Cmin,ss) of laquinimod as assessed from samples collected pre-dose on Days 12, 13 and 14 within the multiple-dose arm | On the last three days of multiple dosing | 
| Systemic exposure of laquinimod | Area under the plasma concentration time curve (AUC) of laquinimod | Over up to 21 days after (last) dose |