Clinical trial NCT05384249: Phase 2b Pivotal Study of Izokibep in Non-infectious, Intermediate-, Posterior- or Pan-uveitis
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Uveitis
Keywords: Non-infectious uveitis
Intermediate-uveitis
Posterior-uveitis
Pan-uveitis
Lead sponsor: ACELYRIN Inc.
Sponsor class: INDUSTRY
First posted: 2022-05-20
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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. This study investigates izokibep in subjects with active non-infectious, intermediate-, posterior- or pan-uveitis requiring high-dose steroids.


Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: Up to Week 52
Secondary outcomes:
measure: Change in best corrected visual acuity (BCVA) from best state achieved
timeFrame: Before Week 10 to Week 24
measure: Change in the National Eye Institute (NEI) Visual Function Questionnarie-25 (VFQ-25) score from best state achieved
timeFrame: Before Week 10 to Week 24
measure: Change in central retinal thickness by Spectral-Domain Optical Coherence Tomography (SD-OCT)
timeFrame: Baseline to Week 10
measure: Change in central retinal thickness by Spectral-Domain Optical Coherence Tomography (SD-OCT) from best state achieved
timeFrame: Week 10 up to Week 52
measure: Proportion of subjects that achieve quiescence
timeFrame: Week 10
measure: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Baseline up to Follow-up (Week 65)
measure: Incidence of serious adverse events (SAEs)
timeFrame: Baseline up to Follow-up (Week 65)
measure: Incidence of clinically significant changes in laboratory values
timeFrame: Baseline up to Follow-up (Week 65)
measure: Incidence of clinically significant changes in vital signs
timeFrame: Baseline up to Follow-up (Week 65)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Clinical Research Site
state: Arizona
city: Bakersfield
country: United States
facility: Clinical Research Site
state: California
city: Beverly Hills
country: United States
facility: Clinical Research Site
state: California
city: Los Angeles
country: United States
facility: Clinical Research Site
state: California
city: Los Angeles
country: United States
facility: Clinical Research Site
state: California
city: Palo Alto
country: United States
facility: Clinical Research Site
state: California
city: Pasadena
country: United States
facility: Clinical Research Site
state: California
city: Redlands
country: United States
facility: Clinical Research Site
state: California
city: Sacramento
country: United States
facility: Clinical Research Site
state: California
city: San Francisco
country: United States
facility: Clinical Research Site
state: California
city: Denver
country: United States
facility: Clinical Research Site
state: Colorado
city: Clearwater
country: United States
facility: Clinical Research Site
state: Florida
city: Marietta
country: United States
facility: Clinical Research Site
state: Georgia
city: Oak Park
country: United States
facility: Clinical Research Site
state: Illinois
city: Indianapolis
country: United States
facility: Clinical Research Site
state: Indiana
city: Hagerstown
country: United States
facility: Clinical Research Site
state: Maryland
city: Waltham
country: United States
facility: Clinical Research Site
state: Massachusetts
city: Detroit
country: United States
facility: Clinical Research Site
state: Michigan
city: Palisades Park
country: United States
facility: Clinical Research Site
state: New Jersey
city: New York
country: United States
facility: Clinical Research Site
state: New York
city: Winston-Salem
country: United States
facility: Clinical Research Site
state: North Carolina
city: Cleveland
country: United States
facility: Clinical Research Site
state: Ohio
city: Cleveland
country: United States
facility: Clinical Research Site
state: Ohio
city: Portland
country: United States
facility: Clinical Research Site
state: Oregon
city: Erie
country: United States
facility: Clinical Research Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Clinical Research Site
state: Pennsylvania
city: Charleston
country: United States
facility: Clinical Research Site
state: South Carolina
city: Nashville
country: United States
facility: Clinical Research Site
state: Tennessee
city: Austin
country: United States
facility: Clinical Research Site
state: Texas
city: Bellaire
country: United States
facility: Clinical Research Site
state: Texas
city: Houston
country: United States
facility: Clinical Research Site
state: Texas
city: Houston
country: United States
facility: Clinical Research Site
state: Texas
city: Houston
country: United States
facility: Clinical Research Site
state: Texas
city: Plano
country: United States
facility: Clinical Research Site
state: Texas
city: Spokane
country: United States
facility: Clinical Research Site
state: Washington
city: Madison
country: United States
facility: Clinical Research Site
state: Wisconsin
city: Graz
country: Austria
facility: Clinical Research Site
city: Salzburg
country: Austria
facility: Clinical Research Site
city: Vienna
country: Austria
facility: Clinical Research Site
city: Brno
country: Czechia
facility: Clinical Research Site
city: Pardubice
country: Czechia
facility: Clinical Research Site
city: Prague
country: Czechia
facility: Clinical Research Site
city: Praha
country: Czechia
facility: Clinical Research Site
city: Lyon
country: France
facility: Clinical Research Site
city: Marseille
country: France
facility: Clinical Research Site
city: Paris
country: France
facility: Clinical Research Site
city: Paris
country: France
facility: Clinical Research Site
city: Paris
country: France
facility: Clinical Research Site
city: Berlin
country: Germany
facility: Clinical Research Site
city: Bonn
country: Germany
facility: Clinical Research Site
city: Hamburg
country: Germany
facility: Clinical Research Site
city: Kiel
country: Germany
facility: Clinical Research Site
city: Leipzig
country: Germany
facility: Clinical Research Site
city: Munster
country: Germany
facility: Clinical Research Site
city: Münster
country: Germany
facility: Clinical Research Site
city: Milano
country: Italy
facility: Clinical Research Site
city: Milano
country: Italy
facility: Clinical Research Site
city: Milan
country: Italy
facility: Clinical Research Site
city: Reggio Emilia
country: Italy
facility: Clinical Research Site
city: Barcelona
country: Spain
facility: Clinical Research Site
city: Barcelona
country: Spain
facility: Clinical Research Site
city: Barcelona
country: Spain
facility: Clinical Research Site
city: Barcelona
country: Spain
facility: Clinical Research Site
city: Madrid
country: Spain
facility: Clinical Research Site
city: Santiago De Compostela
country: Spain
facility: Clinical Research Site (4007)
city: Santiago De Compostela
country: Spain
facility: Clinical Research Site (4008)
city: Valencia
country: Spain
facility: Clinical Research Site
city: Zaragoza
country: Spain
facility: Clinical Research Site
city: Zaragoza
country: Spain
facility: Clinical Research Site
Study officials:
affiliation: ACELYRIN Inc.
name: Donald Betah
role: STUDY_DIRECTOR
References: