POC Study to Evaluate the Efficacy and Safety of ESK-001 in Patients With Active Intermediate, Posterior, or Pan NIU

Study Overview
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Brief Summary
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This is a multi-center, randomized, double-masked, proof-of-concept study in patients with Active Noninfectious Intermediate, Posterior, or Panuveitis.

Detailed Description
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This study will consist of a 2-week screening period (+7 days), 24-week treatment period, followed by a 24-week extension period, and a 4-week follow up period for a total of up to 55 weeks. Each participant will be randomized to receive one of two doses of ESK-001 daily for 24 weeks. Participants that do not meet the treatment failure criteria at Week 24 will continue into the extension period.

Official Title
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A Proof-of-Concept, Randomized, Double-Masked Study to Evaluate the Efficacy and Safety of ESK-001 in Patients With Active Noninfectious Intermediate, Posterior, or Panuveitis (OPTYK-1)

Conditions
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Uveitis Posterior Non-Infectious, Uveitis, Intermediate, Noninfectious Panuveitis

Intervention / Treatment
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* Drug: ESK-001


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Able and willing to provide consent Male and females, age 18 to 70 years Diagnosis of active noninfectious intermediate, posterior or panuveitis Must have active uveitis at Screening in at least one eye as defined by: Active inflammatory chorioretinal and/or inflammatory retinal vascular lesion or lesions, or ≥ 2+ VH in accordance with the NEI/SUN criteria Males and females must use highly effective methods of contraception for the entirety of the study Key Exclusion Criteria: Diagnosis of infectious uveitis Has elevated intraocular pressures or severe glaucoma Positive for HIV, Hepatitis B or C or active or inadequately latent tuberculosis at screening Positive for syphilis at screening Patients with QTcF >450 msec (both males and females) at screening Known active malignancy or history of malignancy within the past 5 years History of chronic drug or alcohol abuse Live vaccines No planned ocular or any other surgery during the course of the study Other protocol-defined inclusion/exclusion criteria apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ESK-001 Dose Level 1<br>ESK-001 administered as an oral tablet | Drug: ESK-001<br>* Oral tablet<br>|
| Experimental: ESK-001 Dose Level 2<br>ESK-001 administered as an oral tablet | Drug: ESK-001<br>* Oral tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare the efficacy between 2 ESK-001 treatment groups for the treatment of active NIU as measured by the proportion of patients failing treatment by Week 24 | The proportion of patients failing treatment for active NIU by Week 24 between 2 ESK-001 treatment groups. Treatment failure is defined as a patient meeting at least 1 of the treatment failure criteria in at least 1 eye at Week 24. | 24 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare the efficacy between 2 ESK-001 treatment groups for the treatment of active NIU as measured by the time to treatment failure on or after Week 24 | Time to treatment failure on or after Week 24 between 2 ESK-001 treatment groups. Time to treatment failure is defined as time to the visit of the first treatment failure as defined per protocol. Median time to treatment failure in each treatment group will be reported and compared. | 24 Weeks | 
| To assess the safety and tolerability of ESK-001 in patients with active NIU by comparing the incidence and proportion of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). | Clinical and laboratory assessments including blood tests, ECGs, hematological measures and physical examinations throughout the study. The number and proportion of TEAEs, SAEs, AEs leading to study discontinuation, and AEs of greater than grade 3 severity will recorded per treatment group and across all groups. | Through study completion, up to 52 weeks | 
| To characterize the pharmacokinetics (PK) of ESK-001 (Cmax) | Plasma concentrations and PK parameters including steady-state maximum observed concentration (Cmax) for ESK-001 at Day 1, Week 24, and Week 48. | Through study completion, up to 48 weeks | 
| To characterize the pharmacokinetics (PK) of ESK-001 (Ctrough) | Plasma concentrations and PK parameters including steady-state trough observed plasma concentration (Ctrough) for ESK-001 at Week 24, and Week 48. | Through study completion, up to 48 weeks |