Phase 2b Pivotal Study of Izokibep in Non-infectious, Intermediate-, Posterior- or Pan-uveitis

Study Overview
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Brief Summary
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Izokibep is a small protein molecule that acts as a selective, potent inhibitor of interleukin-17A, to which it binds with high affinity. This study investigates izokibep in subjects with active non-infectious, intermediate-, posterior- or pan-uveitis requiring high-dose steroids.

Official Title
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A Phase 2b Pivotal Study to Evaluate the Efficacy and Safety of Izokibep in Subjects With Non-infectious, Intermediate-, Posterior- or Pan-uveitis

Conditions
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Uveitis

Intervention / Treatment
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* Drug: Izokibep
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: General Subject has provided signed informed consent including consenting to comply with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. 18 years to 75 years of age Type of Subject and Disease Characteristics Subject is diagnosed with non-infectious intermediate-, posterior- or pan-uveitis Active disease defined by the presence of at least 1 of the following criteria in at least 1 eye despite treatment with stable doses of corticosteroids for at least 2 weeks prior to day 1: Active, inflammatory, chorioretinal and/or inflammatory retinal vascular lesion by dilated indirect ophthalmoscopy, fundus photography, fluorescein angiography (FA), and Spectral-Domain Optical Coherence Tomography (SD-OCT) to determine whether a lesion is active or inactive (the central reading center assessment using FA, fundus photography and/or SD-OCT is required to confirm eligibility prior to day 1). ≥ 2+ vitreous haze (National Eye Institute [NEI]/Standardization of Uveitis Nomenclature [SUN] criteria) by digital indirect ophthalmoscope and fundus photography (the central reading center assessment using fundus photography is required to confirm eligibility prior to day 1). Currently receiving treatment with oral corticosteroids (≥ 7.5 mg/day to ≤ 40 mg/day oral prednisone/prednisolone or corticosteroid equivalent) at a stable dose for at least 2 weeks prior to day 1. Exclusion Criteria: Disease-related Medical Conditions Subject with isolated anterior uveitis Subject with serpiginous choroidopathy Subject with confirmed or suspected infectious uveitis Subject with corneal or lens opacity that precludes visualization of the fundus or that likely requires cataract surgery during the duration of the study Subject with intraocular pressure of ≥ 25 mmHg while on ≥ 2 glaucoma medications or evidence of glaucomatous optic nerve injury Subject with severe vitreous haze that precludes visualization of the fundus prior to first dose of study drug Subject has a contraindication for mydriatic eye drops OR subject cannot be dilated sufficiently well to permit good fundus visualization Subject with best corrected visual acuity (BCVA) < 20 letters (Early Treatment Diabetic Retinopathy Study [ETDRS]) in at least 1 eye prior to first dose of study drug Subject with proliferative or severe non-proliferative retinopathy or clinically significant macular edema due to diabetic retinopathy Subject with neovascular/wet age-related macular degeneration Subject with an abnormality of the vitreo-retinal interface with the potential for macular structural damage independent of the inflammatory process Subject with a history of active scleritis ≤ 12 months of first dose of study drug Other protocol defined Inclusion/Exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Group 1: Placebo subcutaneous once weekly<br>Participants will receive placebo every week to week 51. | Drug: Placebo<br>* Form: Solution for injection Route of administration: Subcutaneous (SC)<br>|
| Experimental: Group 2: Izokibep subcutaneous once weekly<br>Participants will receive izokibep every week to week 51. | Drug: Izokibep<br>* Biologic: IL-17A inhibitor Form: Solution for injection Route of administration: Subcutaneous (SC)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to treatment failure defined as reaching treatment failure by meeting ≥ 1 of the 4 criteria specified in the protocol in at least 1 eye. |  | Week 10 and up to Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects that achieve quiescence |  | Week 10 | 
| Change in best corrected visual acuity (BCVA) from best state achieved |  | Before Week 10 to Week 24 | 
| Change in the National Eye Institute (NEI) Visual Function Questionnarie-25 (VFQ-25) score from best state achieved |  | Before Week 10 to Week 24 | 
| Change in central retinal thickness by Spectral-Domain Optical Coherence Tomography (SD-OCT) |  | Baseline to Week 10 | 
| Change in central retinal thickness by Spectral-Domain Optical Coherence Tomography (SD-OCT) from best state achieved |  | Week 10 up to Week 52 | 
| Incidence of treatment-emergent adverse events (TEAEs) |  | Baseline up to Follow-up (Week 65) | 
| Incidence of serious adverse events (SAEs) |  | Baseline up to Follow-up (Week 65) | 
| Incidence of clinically significant changes in laboratory values |  | Baseline up to Follow-up (Week 65) | 
| Incidence of clinically significant changes in vital signs |  | Baseline up to Follow-up (Week 65) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-infectious uveitis, Intermediate-uveitis, Posterior-uveitis, Pan-uveitis