Clinical trial NCT04717635: Study of Efficacy and Safety of Canakinumab in Japanese Patients With AOSD
Official title: An Open-label, Single-arm, Active-treatment Study to Evaluate Efficacy and Safety of Canakinumab (ACZ885) Administered for at Least 48 Weeks in Japanese Patients With Adult Onset Still's Disease (AOSD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Adult Onset Still's Disease
Keywords: Canakinumab
AOSD
IL-1β
Japanese participants
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2021-01-22
Enrollment: 14
Sex: ALL
Minimum age (years): 16
Maximum age (years): 100
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a phase III study designed to provide efficacy and safety data for canakinumab administered for at least 48 weeks as subcutaneous (s.c.) injection every 4 weeks (q4wk) in Japanese patients with Adult Onset Still's Disease (AOSD). Interim analysis (IA) data at Week 28 and 48 from this study supports a registration submission of canakinumab in the indication of Adult still's disease (ASD) in Japan.


Eligibility criteria: Inclusion Criteria:

* Signed informed consent must be obtained prior to participation in the study. Parent's or legal guardian's written informed consent and child's assent, if appropriate, are required before any assessment is performed for participants \< 20 years of age
* Japanese male and female participants aged ≥ 16 years
* Confirmed diagnosis of AOSD as per Yamaguchi criteria (Yamaguchi M, 1992) with an onset of disease ≥ 16 years of age. Yamaguchi criteria requires at least five criteria, including two major criteria and no exclusion criteria
* Active disease at the time of baseline defined as follows
* Fever (body temperature \> 38°C) due to AOSD for at least 1 day within 1 week before baseline
* At least 2 active joints (tender or swollen)
* CRP ≥ 10 mg/L

Exclusion Criteria:

* Pregnant or nursing (lactating) female participants, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (\> 5 mIU/ mL) at screening visit.
* History of significant hypersensitivity to study drug or to biologics.
* History/evidence of active macrophage activation syndrome or disseminated intravascular coagulation prior to 6 months of enrollment.
* With underlying metabolic, renal, hepatic, infectious or gastrointestinal conditions which in the opinion of the investigator compromises the articipant and/ or places the participant at unacceptable risk for participation in an immunomodulatory therapy.
* With active or recurrent bacterial, fungal or viral infection at the time of enrollment, including participants with evidence of Human Immunodeficiency Virus (HIV) infection, Hepatitis B and Hepatitis C infection.
* Participants with absolute neutrophil count \< 1500/mm3 at screening.

Primary outcomes:
measure: Proportion of participants who achieve adapted American College of Rheumatology (ACR) 30 response at Week 8
timeFrame: Week 8
Secondary outcomes:
measure: Proportion of participants who are able to taper corticosteroids based on success criteria at Week 28.
timeFrame: Week 28
measure: Proportion of participants who achieved adapted ACR 30/50/70/90/100 response criteria at Day 15 and all subsequent visits.
timeFrame: Day 15, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72, 84, 96, 108, 120, 132, 144, End of Study(EOS)(up to Week 152)
measure: Change from baseline in Systemic Feature Score (total score and each components) at Day 15 and all subsequent visits.
timeFrame: Baseline, Day 15, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72, 84, 96, 108, 120, 132, 144, EOS(up to Week 152)
measure: Absolute change from baseline in the component of adapted ACR at Day 15 and all subsequent visits: Physician's global assessment of disease activity
timeFrame: Baseline, Day 15, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72, 84, 96, 108, 120, 132, 144, EOS(up to Week 152)
measure: Absolute change from baseline in the component of adapted ACR at Day 15 and all subsequent visits: Patient's global assessment of disease activity
timeFrame: Baseline, Day 15, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72, 84, 96, 108, 120, 132, 144, EOS(up to Week 152)
measure: Absolute change from baseline in the component of adapted ACR at Day 15 and all subsequent visits: Health Assessment Questionnaire
timeFrame: Baseline, Day 15, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72, 84, 96, 108, 120, 132, 144, EOS(up to Week 152)
measure: Absolute change from baseline in the component of adapted ACR at Day 15 and all subsequent visits: Tender and swollen joint counts
timeFrame: Baseline, Day 15, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72, 84, 96, 108, 120, 132, 144, EOS(up to Week 152)
measure: Absolute change from baseline in the component of adapted ACR at all visits: C-Reactive Protein(CRP)
timeFrame: Baseline, Days 3, 15, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104, 108, 112, 116, 120, 124, 128, 132, 136, 140, 144, 148, EOS(up to Week 152)
measure: Absolute change from baseline in the component of adapted ACR at all visits: Fever assessment
timeFrame: Baseline, Days 3, 15, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104, 108, 112, 116, 120, 124, 128, 132, 136, 140, 144, 148, EOS(up to Week 152)
measure: Change from baseline of corticosteroid dose at all visits after Week 8.
timeFrame: Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104, 108, 112, 116, 120, 124, 128, 132, 136, 140, 144, 148, EOS(up to Week 152)
measure: Presence of rash (typical/atypical) at all visits during study.
timeFrame: Baseline, Day 15, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104, 108, 112, 116, 120, 124, 128, 132, 136, 140, 144, 148, EOS(up to Week 152)
measure: Change from baseline in DAS28-CRP at Day 15 and all subsequent visits.
timeFrame: Baseline, Day 15, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72, 84, 96, 108, 120, 132, 144, EOS(up to Week 152)
measure: Canakinumab concentrations over time
timeFrame: Baseline, Days 3, 15, Weeks 4, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144
measure: Total IL-1β (sum of IL-1β free and bound to canakinumab) level s over time
timeFrame: Baseline, Days 3, 15, Weeks 4, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144
measure: Anti-canakinumab antibody identification and titer
timeFrame: Baseline, Weeks 24, 48, 72, 96, 120
Other outcomes:
Locations:
city: Sapporo city
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Kanazawa
country: Japan
facility: Novartis Investigative Site
state: Ishikawa
city: Yokohama-city
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Iruma-gun
country: Japan
facility: Novartis Investigative Site
state: Saitama
city: Bunkyo ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Chuo ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Mitaka-city
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Chiba
country: Japan
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: