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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Uveitis
• Intervention / Treatment: Drug: Izokibep; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Donald Betah; Phone Number: 805-730-0327; Email: clinicaltrials@acelyrin.com

Study Locations

• Austria
  • Graz, Austria, 8036
    • Recruiting
    • Clinical Research Site
  • Salzburg, Austria, 5020
    • Recruiting
    • Clinical Research Site
  • Vienna, Austria, 1090
    • Recruiting
    • Clinical Research Site
• Czechia
  • Brno, Czechia, 625 00
    • Recruiting
    • Clinical Research Site
  • Pardubice, Czechia, 530 02
    • Recruiting
    • Clinical Research Site
  • Prague, Czechia, 140 52
    • Recruiting
    • Clinical Research Site
  • Praha, Czechia, 128 08
    • Recruiting
    • Clinical Research Site
• France
  • Lyon, France, 69004
    • Recruiting
    • Clinical Research Site
  • Marseille, France, 13008
    • Recruiting
    • Clinical Research Site
  • Paris, France, 75019
    • Recruiting
    • Clinical Research Site
  • Paris, France, 75013
    • Recruiting
    • Clinical Research Site
  • Paris, France, 75014
    • Recruiting
    • Clinical Research Site
• Germany
  • Berlin, Germany, 13355
    • Recruiting
    • Clinical Research Site
  • Bonn, Germany, 53127
    • Recruiting
    • Clinical Research Site
  • Hamburg, Germany, 20246
    • Recruiting
    • Clinical Research Site
  • Kiel, Germany, 24105
    • Recruiting
    • Clinical Research Site
  • Leipzig, Germany, 4103
    • Recruiting
    • Clinical Research Site
  • Munster, Germany, 48145
    • Recruiting
    • Clinical Research Site
  • Münster, Germany, 48149
    • Recruiting
    • Clinical Research Site
• Italy
  • Milan, Italy, 20122
    • Recruiting
    • Clinical Research Site
  • Milano, Italy, 20132
    • Recruiting
    • Clinical Research Site
  • Milano, Italy, 20157
    • Recruiting
    • Clinical Research Site
  • Reggio Emilia, Italy, 42123
    • Recruiting
    • Clinical Research Site
• Spain
  • Barcelona, Spain, 835
    • Recruiting
    • Clinical Research Site
  • Barcelona, Spain, 8017
    • Recruiting
    • Clinical Research Site
  • Barcelona, Spain, 8028
    • Recruiting
    • Clinical Research Site
  • Barcelona, Spain, 8907
    • Recruiting
    • Clinical Research Site
  • Madrid, Spain, 28040
    • Recruiting
    • Clinical Research Site
  • Santiago De Compostela, Spain, 15706
    • Recruiting
    • Clinical Research Site (4007)
  • Santiago De Compostela, Spain, 15706
    • Recruiting
    • Clinical Research Site (4008)
  • Valencia, Spain, 46015
    • Recruiting
    • Clinical Research Site
  • Zaragoza, Spain, 50009
    • Recruiting
    • Clinical Research Site
  • Zaragoza, Spain, 28040
    • Recruiting
    • Clinical Research Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85020-5505
      • Recruiting
      • Clinical Research Site
  • California
    • Bakersfield, California, United States, 93309
      • Recruiting
      • Clinical Research Site
    • Beverly Hills, California, United States, 90211-1841
      • Recruiting
      • Clinical Research Site
    • Los Angeles, California, United States, 90033-1036
      • Recruiting
      • Clinical Research Site
    • Los Angeles, California, United States, 90095-7065
      • Recruiting
      • Clinical Research Site
    • Palo Alto, California, United States, 94303
      • Recruiting
      • Clinical Research Site
    • Pasadena, California, United States, 91107-3747
      • Recruiting
      • Clinical Research Site
    • Redlands, California, United States, 92373
      • Recruiting
      • Clinical Research Site
    • Sacramento, California, United States, 95825
      • Recruiting
      • Clinical Research Site
    • San Francisco, California, United States, 94109
      • Recruiting
      • Clinical Research Site
  • Colorado
    • Lakewood, Colorado, United States, 80228
      • Recruiting
      • Clinical Research Site
  • Florida
    • Clearwater, Florida, United States, 33761
      • Recruiting
      • Clinical Research Site
  • Georgia
    • Marietta, Georgia, United States, 30060-8935
      • Recruiting
      • Clinical Research Site
  • Illinois
    • Oak Park, Illinois, United States, 60304-1096
      • Recruiting
      • Clinical Research Site
  • Indiana
    • Indianapolis, Indiana, United States, 46290
      • Recruiting
      • Clinical Research Site
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Withdrawn
      • Clinical Research Site
  • Maryland
    • Hagerstown, Maryland, United States, 21740-5940
      • Recruiting
      • Clinical Research Site
  • Massachusetts
    • Waltham, Massachusetts, United States, 02451
      • Recruiting
      • Clinical Research Site
  • Michigan
    • Detroit, Michigan, United States, 48201-1423
      • Recruiting
      • Clinical Research Site
  • New Jersey
    • Palisades Park, New Jersey, United States, 07650-2322
      • Recruiting
      • Clinical Research Site
  • New York
    • New York, New York, United States, 10003
      • Recruiting
      • Clinical Research Site
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Recruiting
      • Clinical Research Site
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Recruiting
      • Clinical Research Site
    • Cleveland, Ohio, United States, 44195-0001
      • Recruiting
      • Clinical Research Site
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Clinical Research Site
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16507-1429
      • Recruiting
      • Clinical Research Site
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • Clinical Research Site
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Recruiting
      • Clinical Research Site
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Clinical Research Site
  • Texas
    • Austin, Texas, United States, 78714
      • Recruiting
      • Clinical Research Site
    • Bellaire, Texas, United States, 77401-3218
      • Recruiting
      • Clinical Research Site
    • Houston, Texas, United States, 77025-1756
      • Recruiting
      • Clinical Research Site
    • Houston, Texas, United States, 77494-3286
      • Recruiting
      • Clinical Research Site
    • Houston, Texas, United States, 77030
      • Recruiting
      • Clinical Research Site
    • Plano, Texas, United States, 75075-5025
      • Recruiting
      • Clinical Research Site
  • Washington
    • Spokane, Washington, United States, 99204-2509
      • Recruiting
      • Clinical Research Site
  • Wisconsin
    • Madison, Wisconsin, United States, 53705-3644
      • Recruiting
      • Clinical Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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)
Experimental: Group 2: 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	Time Frame
Proportion of subjects that achieve quiescence	Week 10
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)
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

Collaborators and Investigators

• Sponsor: ACELYRIN Inc.
• Investigators: Study Director: Donald Betah, ACELYRIN Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 23, 2022
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: May 17, 2022
• First Submitted That Met QC Criteria: May 17, 2022
• First Posted (Actual): May 20, 2022

Study Record Updates

• Last Update Posted (Estimated): March 4, 2024
• Last Update Submitted That Met QC Criteria: February 29, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Non-infectious uveitis; Intermediate-uveitis; Posterior-uveitis; Pan-uveitis
• Additional Relevant MeSH Terms: Eye Diseases; Uveal Diseases; Uveitis; Panuveitis
• Other Study ID Numbers: 21103; 2021-006498-49 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No