Safety, Tolerability, and Distribution of Laquinimod Eye Drops : The LION Study (LION)

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

The LION Study is a prospective, 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.

Study Overview

• Status: Recruiting
• Conditions: Inflammation; Uveitis
• Intervention / Treatment: Drug: Laquinimod eye drops

Detailed Description

Participants who fulfill the study eligibility criteria and who are planned to undergo a pars plana vitrectomy will be enrolled in the study. Eligible participants scheduled for a diagnostic vitrectomy may also be enrolled.

The study will consist of two stages:

Stage One - Open label dose escalation:

Up to three subsequent dose-escalation groups will receive Laquinimod eye drops for 2 weeks and samples will be assayed for Laquinimod concentration in aqueous humor, vitreous and plasma.

Stage Two- Randomized, Controlled Comparison of 2 Laquinimod doses:

After the dose escalation cohorts are analysed, 2 Laquinimod doses will be selected for a randomized comparison. The doses in stage 2 will not exceed those studied in stage 1.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94303
      • Recruiting
      • Spencer Center for Vision Research at the Byers Eye Institute
      • Contact: LION Study Team; Phone Number: 650-723-6995; Email: nguyenlabtrials@stanford.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18 years or older
2. Participants who are capable and willing to provide informed consent and follow study instructions.
3. Participants who are scheduled to undergo pars plana vitrectomy (PPV).
4. Participants with intraocular pressure (IOP) ≥ 5 mmHg and ≤22 mmHg in study eye
5. Women who are not pregnant or lactating, are post-menopausal or have undergone a sterilization procedure.

Exclusion Criteria:

1. Participants with active periocular or ocular infectious disease (e.g., blepharitis, scleritis, or conjunctivitis, keratitis or endophthalmitis).
2. Participants with active infectious uveitis
3. Participants with a history of prior intraocular or extraocular surgery within 90 days of study enrollment
4. Participant with a history of intravitreal steroids administered to the study eye within 90 days of enrollment.
5. Participants with a history of intravitreal injection of VEGF inhibitors within 30 days of enrollment
6. 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
7. Use of medication consisting of a strong or moderate inhibitor of CYP3A4 within 2 weeks of Baseline visit (and during the study).
8. Use of medication consisting of a strong inducer of CYP3A4 within 2 weeks of Baseline visit (and during the study)
9. Mild, moderate, or severe hepatic impairment (any of Child-Pugh Score A, B, and C)
10. Moderate or severe renal impairment (GFR ≤60 mL/min)
11. History of HIV disease or other immunodeficiency disorder
12. History of acute hepatitis A (IgM positive), hepatitis B, or hepatitis C
13. History of organ or bone marrow transplant
14. Presence of malignancy under active treatment
15. Any other acute or chronic medical condition that would, in the judgment of the study investigators, reasonably preclude participation in the clinical study
16. Already enrolled in a clinical trial.
17. Any condition that would prevent the investigator from acquiring images of the eye as required per protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; (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; n Laquinimod eye drops 10 mg/ml Dose: Dosing frequency will depend on the groups assigned; Other Names: LAQ eye drops
Experimental: Group 2; (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; n Laquinimod eye drops 10 mg/ml Dose: Dosing frequency will depend on the groups assigned; Other Names: LAQ eye drops
Experimental: Group 3; (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; n Laquinimod eye drops 10 mg/ml Dose: Dosing frequency will depend on the groups assigned; Other Names: LAQ eye drops
Experimental: Stage 2 Comparison Group A; (3 to 6 participants): Participants will receive a dose of Laquinimod eye drops in the study eye for 14 days before the surgery. Frequency to be decided at the end of stage 1.	Drug: Laquinimod eye drops; n Laquinimod eye drops 10 mg/ml Dose: Dosing frequency will depend on the groups assigned; Other Names: LAQ eye drops
Experimental: Stage 2 Comparison Group B; (3 to 6 participants): Participants will receive a dose of Laquinimod as 2 drops in the study eye for 14 days before the surgery. Frequency to be decided at the end of stage 1.	Drug: Laquinimod eye drops; n Laquinimod eye drops 10 mg/ml Dose: Dosing frequency will depend on the groups assigned; Other Names: LAQ eye drops

What is the study measuring?

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 Post operative Day 1 and Post operative Day 8 compared to baseline.	Baseline to end of Study at 22-30days

Collaborators and Investigators

• Sponsor: Quan Dong Nguyen
• Collaborators: Global Ophthalmic Research Center (GORC)

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): August 1, 2024
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: November 29, 2023
• First Submitted That Met QC Criteria: November 29, 2023
• First Posted (Actual): December 7, 2023

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Inflammation; Uveitis; Immunomodulation; Topical; Laquinimod eye drops
• Additional Relevant MeSH Terms: Pathologic Processes; Eye Diseases; Uveal Diseases; Inflammation; Uveitis; Pharmaceutical Solutions; Ophthalmic Solutions
• Other Study ID Numbers: 71341

Drug and device information, study documents

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