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

• Izokibep (Drug): Biologic: IL-17A inhibitor Form: Solution for injection Route of administration: Subcutaneous (SC)
• Placebo (Drug): Form: Solution for injection Route of administration: Subcutaneous (SC)

Primary outcomes

• 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. [Up to Week 52]

Secondary outcomes

• 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]
• Proportion of subjects that achieve quiescence [Week 10]
• 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)]

Sex: All, ages: 18 Years to 75 Years

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

• Donald Betah, Study director, ACELYRIN Inc.