A Study of Laquinimod Eye-drops in Healthy Participants

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Eye Diseases
• Intervention / Treatment: Drug: Laquinimod; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 56
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Eva Bondesson, PhD; Phone Number: +46 46 192000; Email: eva.bondesson@activebiotech.com

Study Locations

• Austria
  • Vienna, Austria
    • Clinical trial center at Medical University Vienna

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Laquinimod - Single Ascending Doses; One single dose of laquinimod eye-drops. There are up to four planned dose levels.	Drug: Laquinimod; Eye-drops; Other Names: TV-5600; ABR-215062
Placebo Comparator: Placebo - Single Ascending Doses; One single dose of placebo eye-drops.	Drug: Placebo; Eye-drops
Experimental: Laquinimod - Multiple Ascending Doses; 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; Eye-drops; Other Names: TV-5600; ABR-215062
Placebo Comparator: Placebo - Multiple Ascending Doses; Eye-drops administered once daily for 14-21 days.	Drug: Placebo; Eye-drops

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Active Biotech AB
• Investigators: Principal Investigator: Gerhard Garhöfer, MD PhD, Clinical trial center at Medical University Vienna

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2021
• Primary Completion (Anticipated): January 1, 2023
• Study Completion (Anticipated): March 1, 2023

Study Registration Dates

• First Submitted: December 6, 2021
• First Submitted That Met QC Criteria: January 10, 2022
• First Posted (Actual): January 11, 2022

Study Record Updates

• Last Update Posted (Actual): January 18, 2023
• Last Update Submitted That Met QC Criteria: January 17, 2023
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases
• Other Study ID Numbers: 21LAQ01; 2021-004029-60 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No