Phase 1 Open-label Study to Evaluate Efficacy and Tolerability of TLC399 in Patients With Macular Edema Due to RVO

Study Overview
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Brief Summary
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To determine whether TLC399 (ProDex) provides an ideal, safe, long-acting, dexamethasone sodium phosphate (DSP) delivery system for the treatment of macular edema due to retinal vein occlusion (RVO).

Detailed Description
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<Part 1> An open-label, sequential dose escalation part to determine the DLT of TLC399 (ProDex) in patients with macular edema due to central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO). The safety results should be evaluated by Safety Monitor Committee regularly every 6 months and after last patient of each cohort completes DLT observation period. The SMC would advise or give permission for further dose escalation, de-escalation, or any study design adjustment. After the study drug administration, these patients will continue to be evaluated for efficacy and safety outcomes up to a period of 12 months unless the patient is withdrawn or discontinues the study. Group R1: 0.24 mg DSP with 100 mM PL (20 µL) Group 1: 0.36 mg DSP with 100 mM PL (30 µL) Group 2: 0.6 mg DSP with 100 mM PL (50 µL) Group 3: 0.6 mg DSP with 50 mM PL (50 µL) <Part 2> An open-label, single-arm design to investigate the use of TLC399 (ProDex) in patients with macular edema due to CRVO or BRVO in one dose level selected from Part 1. The enrollment of subjects for analysis will include approximately 20 patients in total, inclusive of Part 1 and Part 2 for the selected dose group. The safety and efficacy outcomes will be assessed for up to 12 months.

Official Title
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Phase I/II Trial of TLC399 (ProDex) in Patients With Macular Edema Due to Retinal Vein Occlusion (RVO)

Conditions
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Central Retinal Vein Occlusion With Macular Edema, Branch Retinal Vein Occlusion With Macular Edema

Intervention / Treatment
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* Drug: TLC399


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, > 20 years of age. Patients with macular edema due to CRVO or BRVO diagnosed within 36 months. BCVA score of 20/40 to 20/400 by chart ETDRS in the study eye. Mean central subfield thickness ≥350uM on Spectral/Fourier domain by OCT measurements in the study eye. Willing and able to comply with the study procedure and sign a written informed consent. Exclusion Criteria: Macular edema due to diabetic retinopathy or other etiologies. Brisk afferent pupillary defect. Stroke or myocardial infarction within 3 months. Uncontrolled systemic disease, or poorly controlled hypertension, or poorly controlled diabetes. Any ocular condition that in the opinion of the Investigator would prevent a 15-letter gain in visual acuity. Presence of an epiretinal membrane in the study eye which is the primary cause of macular edema, or is severe enough to prevent gain in visual acuity despite reduction in macular edema. History of clinically significant IOP elevation in response to steroid treatment. History of glaucoma or optic nerve head change consistent with glaucoma damage, and/or glaucomatous visual field loss in both eyes. Active ocular hypertension ≥21mmHg or history of treated ocular hypertension in the study eye. Aphakia or presence of anterior chamber intraocular lens in the study eye. Active retinal neovascularization in the study eye. Active or history of choroidal neovascularization in the study eye. History of central serous chorioretinopathy in either eye. Presence of rubeosis iridis in the study eye. Any active ocular infection in either eye. History of herpetic ocular infection in the study eye or adnexa. Presence of active or inactive toxoplasmosis in either eye. Presence of visible scleral thinning or ectasia in the study eye. Media opacity in the study eye that precludes clinical and photographic evaluation. Intraocular surgery in the stydy eye within 6 months. History of pars plana vitrectomy, radial optic neurotomy, or sheathotomy in the study eye. Anticipated need for ocular surgery in the study eye during the 12-months study period. Use of hemodilution for the treatment of RVO within 3 months. Use of any intraocular anti-VEGF therapy in the study eye. Use of laser of any type in the study eye within 3 months. Previous use of intravitreal steroids in the study eye within 6 months. Periocular depot of steroids to the study eye within 1 month. Use of systemic sterois, or warfarin/heparin within 1 month. Use of immunosuppressants, immunomodulators, antimetabolites, and/or alkylating agents within 6 months. BCVA score <34 letters in the non-study eye. Known allergy or hypersensitivity to the study medication or its components. Known allergy or contraindication to the use of fluorescein or povidone iodine or contraindication to pupil dilation in either eye. Female patients who are pregnant, nursing, or planning a pregnancy, or who are of childbearing potential and not using a reliable means of contraception. Current enrollment in an investigational drug or device study or participation in such a study within 90 days. Patient has a condition or is in a situation which will interfere with the patient's ability to comply with the dosig and visit schedules and the protocol evaluations or may not suitable for this study.

Ages Eligible for Study
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Minimum Age: 20 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: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TLC399 (Group 1)<br>TLC399 is manufactured with the proprietary lipid formulation in lyophilized form (BioSeizer) for the reconstitution with the aqueous DSP. | Drug: TLC399<br>* Dose-escalation Study from 100 mM PL (20 µL) with 0.24 mg DSP to 100 mM PL (20 µL) with0.36 mg DSP to 100 mM PL (20 µL) with 0.6 mg DSP to 50 mM PL (10 µL) with 0.6 mg DSP.<br>* Other names: TLC399 (BioSeizer);|
| Experimental: TLC399 (Group R1)<br>TLC399 is manufactured with the proprietary lipid formulation in lyophilized form (BioSeizer) for the reconstitution with the aqueous DSP. | Drug: TLC399<br>* Dose-escalation Study from 100 mM PL (20 µL) with 0.24 mg DSP to 100 mM PL (20 µL) with0.36 mg DSP to 100 mM PL (20 µL) with 0.6 mg DSP to 50 mM PL (10 µL) with 0.6 mg DSP.<br>* Other names: TLC399 (BioSeizer);|
| Experimental: TLC399 (Group 2)<br>TLC399 is manufactured with the proprietary lipid formulation in lyophilized form (BioSeizer) for the reconstitution with the aqueous DSP. | Drug: TLC399<br>* Dose-escalation Study from 100 mM PL (20 µL) with 0.24 mg DSP to 100 mM PL (20 µL) with0.36 mg DSP to 100 mM PL (20 µL) with 0.6 mg DSP to 50 mM PL (10 µL) with 0.6 mg DSP.<br>* Other names: TLC399 (BioSeizer);|
| Experimental: TLC399 (Group 3)<br>TLC399 is manufactured with the proprietary lipid formulation in lyophilized form (BioSeizer) for the reconstitution with the aqueous DSP. | Drug: TLC399<br>* Dose-escalation Study from 100 mM PL (20 µL) with 0.24 mg DSP to 100 mM PL (20 µL) with0.36 mg DSP to 100 mM PL (20 µL) with 0.6 mg DSP to 50 mM PL (10 µL) with 0.6 mg DSP.<br>* Other names: TLC399 (BioSeizer);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Dose-limiting Toxicity (DLT) | Ocular AEs | 4 weeks | 
| Part 2: Safety Assessment: Number of SAEs and Treatment-related Severe AEs | Number of SAEs and treatment-related severe AEs | Up to 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Macular Edema, RVO