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

Sponsor

ACELYRIN Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05384249

Collaborator

(none)

120

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Izokibep is a small protein molecule that acts as a selective, potent inhibitor of interleukin-17A, to which it binds with high affinity. Izokibep has been investigated in non-clinical and clinical studies including healthy subjects and patients with psoriasis and psoriatic arthritis and is currently being studied in uveitis, axial spondyloarthritis and hidradenitis suppurativa. This study investigates izokibep in subjects with active non-infectious, intermediate-, posterior- or pan-uveitis requiring high-dose steroids.

Condition or Disease	Intervention/Treatment	Phase
Uveitis	Drug: Izokibep Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Aug 1, 2022

Anticipated Primary Completion Date :

Aug 1, 2024

Anticipated Study Completion Date :

Aug 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Group 1: Placebo subcutaneous once weekly Participants will receive placebo every week to week 51.	Drug: Placebo Form: Solution for injection Route of administration: Subcutaneous (SC)
Placebo Comparator: Group 2: Placebo subcutaneous every 2 weeks Participants will receive placebo every 2 weeks up to week 50.	Drug: Placebo Form: Solution for injection Route of administration: Subcutaneous (SC)
Experimental: Group 3: Izokibep subcutaneous once weekly Participants will receive izokibep every week to week 51.	Drug: Izokibep Biologic: IL-17A inhibitor Form: Solution for injection Route of administration: Subcutaneous (SC)
Experimental: Group 4: Izokibep subcutaneous every two weeks Participants will receive izokibep every 2 weeks to week 50.	Drug: Izokibep Biologic: IL-17A inhibitor Form: Solution for injection Route of administration: Subcutaneous (SC)

Outcome Measures

Primary Outcome Measures

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

Proportion of subjects that achieve quiescence [Week 10]
Change in best corrected visual acuity (BCVA) from best state achieved [Week 10 to Week 24]
Change in the National Eye Institute (NEI) Visual Function Questionnarie-25 (VFQ-25) score from best state achieved [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)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

General

Subject or legally authorized representative 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 intervention
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 intervention
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 intervention

Other protocol defined Inclusion/Exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Research Site	Lakewood	Colorado	United States	80228
2	Clinical Research Site	Marietta	Georgia	United States	30060-8935
3	Clinical Research Site	Palisades Park	New Jersey	United States	07650-2322
4	Clinical Research Site	Erie	Pennsylvania	United States	16507-1429
5	Clinical Research Site	Bellaire	Texas	United States	77401-3218
6	Clinical Research Site	Houston	Texas	United States	77025-1756
7	Clinical Research Site	Plano	Texas	United States	75075-5025
8	Clinical Research Site	Madison	Wisconsin	United States	53705-3644