Summary
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.
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.
Eligibility Criteria
Age Range: 18 years to No maximum
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