ONO-4059 Study in Patients With Steroid-resistant Pemphigus

ONO-4059-10:Multicenter, Placebo-controlled, Randomized, Double-blind, Phase 3 Study in Patients With Steroid-resistant Pemphigus (BRILLIANT Study)

ONO-4059-10:Multicenter, placebo-controlled, randomized, double-blind, Phase 3 study in patients with steroid-resistant pemphigus

Study Overview

• Status: Recruiting
• Conditions: Pemphigus; Steroid-resistant Pemphigus
• Intervention / Treatment: Drug: ONO-4059; Drug: ONO-4059 placebo

• Study Type: Interventional
• Enrollment (Estimated): 34
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: North America Clinical Trial Support Desk; Phone Number: +18665877745(Toll-Free); Email: clinical_trial@ono-pharma.com
• Study Contact Backup: Name: International Clinical Trial Support Desk; Phone Number: +17162141777(Standard); Email: clinical_trial@ono-pharma.com

Study Locations

• Japan
  • Aichi, Japan
    • Recruiting
    • Nagoya City University Hospital
  • Aichi, Japan
    • Recruiting
    • Ichinomiya Municipal Hospital
  • Ehime, Japan
    • Recruiting
    • Ehime University Hospital
  • Fukuoka, Japan
    • Recruiting
    • Kurume University Hospital
  • Fukushima, Japan
    • Recruiting
    • Fukushima Medical University Hospital
  • Gunma, Japan
    • Recruiting
    • Gunma University Hospital
  • Hokkaido, Japan
    • Recruiting
    • Hokkaido University Hospital
  • Kagoshima, Japan
    • Recruiting
    • Kagoshima University Hospital
  • Kanagawa, Japan
    • Recruiting
    • Tokai University Hospital
  • Kanagawa, Japan
    • Recruiting
    • Yokohama City University Hospital
  • Kanagawa, Japan
    • Recruiting
    • St.Marianna University School of Medicine hospital
  • Kumamoto, Japan
    • Recruiting
    • Kumamoto University Hospital
  • Kyoto, Japan
    • Recruiting
    • University Hospital Kyoto Prefectural University of Medicine
  • Niigata, Japan
    • Recruiting
    • Niigata University Medical & Dental Hospital
  • Okayama, Japan
    • Recruiting
    • Kawasaki Medical School Hospital
  • Okinawa, Japan
    • Recruiting
    • University of the Ryukyus Hospital
  • Osaka, Japan
    • Recruiting
    • Kindai University Hospital
  • Osaka, Japan
    • Recruiting
    • Osaka Metropolitan University Hospital
  • Saitama, Japan
    • Recruiting
    • Saitama Medical Center
  • Shiga, Japan
    • Recruiting
    • Shiga University of Medical Science Hospital
  • Tochigi, Japan
    • Recruiting
    • Jichi Medical University Hospital
  • Tokyo, Japan
    • Recruiting
    • Keio University Hospital
  • Tokyo, Japan
    • Recruiting
    • Tokyo Medical and Dental University Hospital
  • Tokyo, Japan
    • Recruiting
    • Tokyo Women's Medical University Hospital
  • Yamagata, Japan
    • Not yet recruiting
    • Yamagata University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with a diagnosis of pemphigus
• Patients with a re-increase in the pemphigus disease area index (PDAI) score before oral corticosteroid tapering to 10mg/day of prednisolone (PSL) equivalent

Exclusion Criteria:

• Patients with an active infection
• Patients with malignancy
• Patients with past history of serious allergy or anaphylaxis

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: Placebo	Drug: ONO-4059 placebo; Placebo will be administered orally once daily after a meal (breakfast, lunch, or dinner).
Active Comparator: ONO-4059	Drug: ONO-4059; Tirabrutinib is a Bruton's Tyrosine Kinase Inhibitor. Tirabrutinib will be administered orally at a dose of 80 mg once daily after a meal (breakfast, lunch, or dinner).; Other Names: Tirabrutinib hydrochloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of patients with a Complete response (CR) or Partial response (PR) at 52 weeks, and maintaining complete/partial remission at 52 weeks from initial remission achievement.	CR: Absence of pemphigus-related blisters or new erythema that lasts for 8 weeks during treatment with ONO-4059 plus an oral corticosteroid (≤10 mg/day prednisolone-equivalent) or minimal adjunctive therapy. PR: Occurrence of only a transient lesion that resolves within 1 week without an increased dose of an oral corticosteroids, without treatment, or with a topical corticosteroid, etc., during treatment with ONO-4059 plus an oral corticosteroid (≤10 mg/day prednisolone-equivalent) or minimal adjunctive therapy for 8 weeks.	52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Remission rate	remission rate [proportion of subjects who achieve complete or partial remission], complete remission rate, partial remission rate	52 weeks
Pemphigus Disease Area Index (PDAI) score	Pemphigus Disease Area Index (PDAI). PDAI activity score cutoffs were defined as 0 to 8 for mild, 9 to 24 for moderate, and 25 or higher for severe disease.	52 weeks
Efficacy 1 rate (proportion of subjects for whom the definition of efficacy 1 is applicable)	Definition of efficacy 1: Decreases in PDAI score and oral corticosteroid dose from baseline	52 weeks
Efficacy 2 rate (proportion of subjects for whom the definition of efficacy 2 is applicable)	Definition of efficacy 2: PDAI score is 0 and oral corticosteroid dose <= 10 mg/day	52 weeks
Disease control rate (proportion of subjects for whom the definition of disease control is applicable)	Definition of disease control: Formation of nascent lesions stops and existing lesions begin to resolve	52 weeks
Rescue therapy rate	Proportion of subjects who received rescue therapy	52 weeks
Pemphigus autoantibody titer	Anti-desmoglein 1 antibodies, anti-desmoglein 3 antibodies	52 weeks
Oral corticosteroid dose	At the equivalent dose of prednisolone	52 weeks
QOL evaluation	The Dermatology Life Quality Index (DLQI) score is measured by questionnaire.	52 weeks
Adverse events and adverse drug reactions		52 weeks
Clinical laboratory tests	Number of participants with clinical laboratory abnormalities (including haematology, clinical chemistry and urinalysis).	52 weeks
12-lead ECG	Heart rate, RR interval, PR interval, QRS duration, QT interval and QTcF	52 weeks
Vital signs	Systolic/diastolic blood pressure	52 weeks
Vital signs	Body temperature	52 weeks
Immunological tests	Immunoglobulin G and its subclasses (IgG 1, 2, 3, and 4), immunoglobulin M, immunoglobulin A, peripheral blood B-cell count, and peripheral blood T-cell count	52 weeks
Plasma ONO-4059 concentration		52 weeks
Immunophenotyping	Level of naive-B cell, memory-B cell, plasmablast etc.	52 weeks
Cytokines and chemokines	Level of tumor necrosis factor-α, interleukin (IL)-8, IL-13, IL-17, C-X-C motif chemokine ligand 13 etc.	52 weeks
RNA sequencing		52 weeks
Anti-virus antibody		52 weeks
Recurrence rate (the proportion of subjects meeting the definition of recurrence) and time to recurrence	Definition of recurrence: In patients with controlled disease, the presence of three or more new lesions in a month that do not spontaneously resolve within a week, or the expansion of existing lesions Definition of time to recurrence: The period from achieving disease control to recurrence	52 weeks

Collaborators and Investigators

• Sponsor: Ono Pharmaceutical Co. Ltd
• Investigators: Study Director: Project Leader, Ono Pharmaceutical Co. Ltd

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2022
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): March 31, 2029

Study Registration Dates

• First Submitted: November 7, 2024
• First Submitted That Met QC Criteria: November 18, 2024
• First Posted (Actual): November 20, 2024

Study Record Updates

• Last Update Posted (Actual): January 7, 2026
• Last Update Submitted That Met QC Criteria: January 5, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Autoimmune Diseases; Immune System Diseases; Skin Diseases; Skin Diseases, Vesiculobullous; Skin and Connective Tissue Diseases; Pemphigus; tirabrutinib
• Other Study ID Numbers: ONO-4059-10; jRCT2031220043 (Registry Identifier: Japan Registry of Clinical Trials)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No