Pemphigus, Steroid-resistant Pemphigus
Conditions
Brief summary
ONO-4059-10:Multicenter, placebo-controlled, randomized, double-blind, Phase 3 study in patients with steroid-resistant pemphigus
Interventions
DRUGONO-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).
DRUGONO-4059 placebo
Placebo will be administered orally once daily after a meal (breakfast, lunch, or dinner).
Sponsors
Ono Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 52 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Remission rate | 52 weeks | remission rate \[proportion of subjects who achieve complete or partial remission\], complete remission rate, partial remission rate |
| Pemphigus Disease Area Index (PDAI) score | 52 weeks | 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. |
| Efficacy 1 rate (proportion of subjects for whom the definition of efficacy 1 is applicable) | 52 weeks | Definition of efficacy 1: Decreases in PDAI score and oral corticosteroid dose from baseline |
| Efficacy 2 rate (proportion of subjects for whom the definition of efficacy 2 is applicable) | 52 weeks | Definition of efficacy 2: PDAI score is 0 and oral corticosteroid dose \<= 10 mg/day |
| Disease control rate (proportion of subjects for whom the definition of disease control is applicable) | 52 weeks | Definition of disease control: Formation of nascent lesions stops and existing lesions begin to resolve |
| Rescue therapy rate | 52 weeks | Proportion of subjects who received rescue therapy |
| Pemphigus autoantibody titer | 52 weeks | Anti-desmoglein 1 antibodies, anti-desmoglein 3 antibodies |
| Oral corticosteroid dose | 52 weeks | At the equivalent dose of prednisolone |
| QOL evaluation | 52 weeks | The Dermatology Life Quality Index (DLQI) score is measured by questionnaire. |
| Adverse events and adverse drug reactions | 52 weeks | — |
| Clinical laboratory tests | 52 weeks | Number of participants with clinical laboratory abnormalities (including haematology, clinical chemistry and urinalysis). |
| 12-lead ECG | 52 weeks | Heart rate, RR interval, PR interval, QRS duration, QT interval and QTcF |
| Vital signs | 52 weeks | Systolic/diastolic blood pressure |
| Immunological tests | 52 weeks | 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 |
| Plasma ONO-4059 concentration | 52 weeks | — |
| Immunophenotyping | 52 weeks | Level of naive-B cell, memory-B cell, plasmablast etc. |
| Cytokines and chemokines | 52 weeks | Level of tumor necrosis factor-α, interleukin (IL)-8, IL-13, IL-17, C-X-C motif chemokine ligand 13 etc. |
| RNA sequencing | 52 weeks | — |
| Anti-virus antibody | 52 weeks | — |
| Recurrence rate (the proportion of subjects meeting the definition of recurrence) and time to recurrence | 52 weeks | 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 |
Countries
Japan
Contacts
STUDY_DIRECTORProject Leader
Ono Pharmaceutical Co., Ltd.
Outcome results
None listed