- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05814159
A Study of Anakinra in Japanese Patients With Still's Disease (SJIA and AOSD)
A Randomized, Double-blind, Placebo-controlled, Multicenter, Phase 3 Efficacy and Safety Study of Subcutaneous Anakinra in Japanese Patients With Still's Disease (SJIA and AOSD)
Study Overview
Status
Intervention / Treatment
Detailed Description
The study consists of a 2-Week, randomized, double-blind, placebo-controlled period, followed by a 52-Week open-label phase treatment with anakinra. After the last dose of anakinra at Week 54, the safety will be evaluated at a Safety Follow-up visit i.e., at Week 58.
The primary endpoint will be evaluated at Week 2 visit. Patients will be randomly assigned to either anakinra or placebo for a period of 2 weeks.
Study Type
Enrollment (Estimated)
Phase
- Phase 3
Contacts and Locations
Study Contact
- Name: Yuichiro Nakayama
- Email: yuichiro.nakayama@sobi.com
Study Contact Backup
- Name: Ioannis Kottakis, MD
- Phone Number: +41-615087213
- Email: ioannis.kottakis@sobi.com
Study Locations
-
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Chiba
-
Chiba-shi, Chiba, Japan
- Recruiting
- Chiba Children's Hospital
-
Contact:
- Minako Tomiita, MD
-
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Fukuoka
-
Kurume-shi, Fukuoka, Japan
- Recruiting
- Kurume University Hospital
-
Contact:
- Ryuta Nishikomri, MD
-
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Fukushima
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Fukushima-shi, Fukushima, Japan
- Recruiting
- Fukushima Medical University Hospital
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Contact:
- Kiyoshi Migita, MD
-
-
Hokkaido
-
Sapporo, Hokkaido, Japan
- Recruiting
- Sapporo Medical University Hospital
-
Contact:
- Hiroki Takahashi, MD
-
-
Hyogo
-
Kobe, Hyogo, Japan
- Recruiting
- Hyogo prefectural Kobe Children's Hospital
-
Contact:
- Yasuo Nakagishi, MD
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Kobe city, Hyogo, Japan
- Recruiting
- Kobe University Hospital
-
Contact:
- Jun Saegusa, MD
-
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Kanagawa
-
Kawasaki, Kanagawa, Japan
- Recruiting
- St. Marianna University Hospital
-
Contact:
- Kazuko Yamazaki, MD
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Yokohama, Kanagawa, Japan
- Recruiting
- Yokohama City University Hospital (Hematology and Clinical Immunology)
-
Contact:
- Yohei Kirino, MD
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Yokohama, Kanagawa, Japan
- Recruiting
- Yokohama City University Hospital (pediatrics)
-
Contact:
- Shuichi Ito, MD
-
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Nagano
-
Matsumoto, Nagano, Japan
- Recruiting
- Shinshu University
-
Contact:
- Yasuhiro shimoijma, MD
-
-
Nagasaki
-
Nagasaki-shi, Nagasaki, Japan
- Recruiting
- Nagasaki University Hospital
-
Contact:
- Atsushi Kawakami, MD
-
-
Osaka
-
Takatsuki, Osaka, Japan
- Recruiting
- Osaka Medical and Pharmaceutical University Hospital
-
Contact:
- Yuka Ozeki, MD
-
-
Saitama
-
Iruma-gun, Saitama, Japan
- Recruiting
- Saitama Medical University Hospital
-
Contact:
- Toshihide Mimura, MD
-
Saitama-shi, Saitama, Japan
- Recruiting
- Saitama Prefectural Children's Medical Center
-
Contact:
- Satoshi Sato, MD
-
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Shimane
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Izumo-shi, Shimane, Japan
- Recruiting
- Shimane University Hospital
-
Contact:
- Masahiro Kondo, MD
-
-
Shizuoka
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Hamamatsu city, Shizuoka, Japan
- Recruiting
- Hamamatsu University Hospital
-
Contact:
- Noriyoshi Ogawa, MD
-
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Tokyo
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Bunkyō-Ku, Tokyo, Japan
- Recruiting
- Tokyo Medical and Dental University Hospital
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Contact:
- Masaki Shimizu, MD
-
Ota-ku, Tokyo, Japan
- Recruiting
- Toho University Omori Medical Center
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Contact:
- Toshihiro Nanki, MD
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Shinjuku-Ku, Tokyo, Japan
- Recruiting
- Tokyo Women's Medical University Hospital
-
Contact:
- Takako Miyamae, MD
-
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Male and female patients, 8 months of age or older with a body weight ≥ 10 kg
- Diagnosis of Still's disease
- If < 16 years of age at disease onset, the diagnosis is madeaccording to adapted ILAR criteria i.e., CARRA criteria for SJIA. If ≥ 16 years of age at disease onset, the diagnosis is made according to Yamaguchi criteria for AOSD.
- Active disease confirmed by the following three signs and symptoms. a. Active arthritis in ≥ 1 joint. b. CRP > 30 mg/L. c. At least one fever episode (≥ 38.0 degree Celsius) attributable to the disease within one week before enrollment.
- The result of tuberculosis test within 8 weeks prior to enrollment is negative.
Exclusion Criteria:
- Previous or current treatment with anakinra, or any other Interleukin-1 (IL-1) inhibitor except for canakinumab. Previous treatment with canakinumab is allowed if canakinumab was discontinued for reasons other than lack of efficacy and after a washout period of minimum 130 days. Patients who have discontinued canakinumab because of insufficient effect or refractory disease are not allowed to be enrolled in the study.
Use of the following therapies prior to enrollment.
- Narcotic analgesics within 24 hours prior to enrollment.
- Diaminodiphenyl sulfone within 1 week prior to enrollment or etanercept within 2 weeks prior to enrollment.
- Intraarticular, intramuscular, or intravenous administration of glucocorticoids within 72h(3 days) prior to enrollment, or intravenous immunoglobulin within 4 weeks prior to enrollment.
- Intravenous immunoglobulins with proven Still's disease modifying effect, leflunomide, infliximab, or adalimumab within 8 weeks prior to enrollment.
- Thalidomide within 72h(3 days) prior to enrollment, cyclosporine within 5 weeks prior to enrollment, mycophenolate mofetil within 1 week prior to enrollment, 6-mercaptopurine within 48h(2 days) prior to enrollment, azathioprine within 72h(3 days) prior to enrollment, cyclophosphamide within 96h(4 days) prior to enrollment, chlorambucil (not approved inJapan) within 48h(2 days) prior to enrollment, or any other immunosuppressants within 12 weeks prior to enrollment.
- Tocilizumab within 4 weeks prior to enrollment or any other immunomodulatory medications within 4 half-lives prior to enrollment.
- Rituximab within 13 weeks prior to enrollment.
- Canakinumab within 130 days prior to enrollment
- Live vaccines within 4 weeks prior to enrollment.
- Known presence or suspicion of active, chronic, or recurrent bacterial, fungal, or viral infections, including but not limited to tuberculosis, HIV infection, Covid-19 infection, or hepatitis B or C infection at baseline. Patients with acute or chronic HBV.
- Clinical evidence of liver disease or liver injury as indicated by presence of abnormal liver tests.
- Presence of severe chronic kidney disease (CKD) grades 4 and 5.
- Presence of neutropenia (absolute neutrophil count [ANC] < 1.5 x 10^9/L).
- Presence of thrombocytopenia (platelets count < 100 x 10^9/L).
- Presence or suspicion of MAS at baseline.
- History or diagnosis of MAS within the last 4 weeks prior to enrollment.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Anakinra
100 mg/day or 2 mg/kg/day of subcutaneous anakinra for those with a body weight ≥50 kg or <50 kg, respectively.
|
sub cutaneous daily injection
Other Names:
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Placebo Comparator: Placebo
Corresponding volume to 100 mg/day or 2 mg/kg/day
|
sub cutaneous daily injection
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
An improvement of ≥ 30% from baseline in physician global assessment of disease activity (visual analogue scale [VAS]).
Time Frame: Week 2
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ACR30 response with absence of fever attributable to the disease during the 7 days
|
Week 2
|
An improvement of ≥ 30% from baseline in patient/parent global assessment of overall well-being (VAS).
Time Frame: Week 2
|
ACR30 response with absence of fever attributable to the disease during the 7 days
|
Week 2
|
An improvement of ≥ 30% from baseline in number of joints with active arthritis.
Time Frame: Week 2
|
ACR30 response with absence of fever attributable to the disease during the 7 days
|
Week 2
|
An improvement of ≥ 30% from baseline in number of joints with limitation of motion.
Time Frame: Week 2
|
ACR30 response with absence of fever attributable to the disease during the 7 days
|
Week 2
|
An improvement of ≥ 30% from baseline in assessment of physical function: Child health assessment questionnaire (CHAQ)/Stanford health assessment questionnaire (SHAQ).
Time Frame: Week 2
|
ACR30 response with absence of fever attributable to the disease during the 7 days
|
Week 2
|
An improvement of ≥ 30% from baseline in C-reactive protein (CRP) (mg/L).
Time Frame: Week 2
|
ACR30 response with absence of fever attributable to the disease during the 7 days
|
Week 2
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in CRP.
Time Frame: Week 2
|
To demonstrate the efficacy of anakinra compared to placebo in reducing inflammation in Still's disease.
|
Week 2
|
Change in ferritin.
Time Frame: Week 2
|
To demonstrate the efficacy of anakinra compared to placebo in reducing inflammation in Still's disease.
|
Week 2
|
Change in haemoglobin.
Time Frame: Week 2
|
To demonstrate the efficacy of anakinra compared to placebo in reducing inflammation in Still's disease.
|
Week 2
|
Change in platelets count.
Time Frame: Week 2
|
To demonstrate the efficacy of anakinra compared to placebo in reducing inflammation in Still's disease.
|
Week 2
|
Change in white blood cells count.
Time Frame: Week 2
|
To demonstrate the efficacy of anakinra compared to placebo in reducing inflammation in Still's disease.
|
Week 2
|
Absence of fever during the 24 hours preceding the evaluation visit at Week 1.
Time Frame: Week 1
|
To demonstrate early onset of efficacy of anakinra compared to placebo in Still's disease.
|
Week 1
|
Absence of rash during the 24 hours preceding the evaluation visit at Week 1.
Time Frame: Week 1
|
To demonstrate early onset of efficacy of anakinra compared to placebo in Still's disease.
|
Week 1
|
ACR30 response with absence of fever during the 24 hours preceding the evaluation visit at Week 1.
Time Frame: Week 1
|
To demonstrate early onset of efficacy of anakinra compared to placebo in Still's disease.
|
Week 1
|
ACR50 response with absence of fever during the 24 hours preceding the evaluation visit at Week 1.
Time Frame: Week 1
|
To demonstrate early onset of efficacy of anakinra compared to placebo in Still's disease.
|
Week 1
|
ACR70 response with absence of fever during the 24 hours preceding the evaluation visit at Week 1.
Time Frame: Week 1
|
To demonstrate early onset of efficacy of anakinra compared to placebo in Still's disease.
|
Week 1
|
Change in physician global assessment of disease activity, measured on a VAS from no pain (0 mm) to very severe (100 mm).
Time Frame: Week 1
|
To demonstrate early onset of efficacy of anakinra compared to placebo in Still's disease.
|
Week 1
|
Change in patient/parent global assessment of overall well-being, measured on a VAS from no pain (0 mm) to very severe (100 mm).
Time Frame: Week 1
|
To demonstrate early onset of efficacy of anakinra compared to placebo in Still's disease.
|
Week 1
|
Change in patient/parent global assessment of disease related pain, measured on a VAS from no pain (0 mm) to very severe (100 mm).
Time Frame: Week 1
|
To demonstrate early onset of efficacy of anakinra compared to placebo in Still's disease.
|
Week 1
|
Change in swelling joints count.
Time Frame: Week 1
|
To demonstrate early onset of efficacy of anakinra compared to placebo in Still's disease.
|
Week 1
|
Change in tender joints count.
Time Frame: Week 1
|
To demonstrate early onset of efficacy of anakinra compared to placebo in Still's disease.
|
Week 1
|
Change in CRP.
Time Frame: Week 1
|
To demonstrate early onset of efficacy of anakinra compared to placebo in Still's disease.
|
Week 1
|
Change in ferritin.
Time Frame: Week 1
|
To demonstrate early onset of efficacy of anakinra compared to placebo in Still's disease.
|
Week 1
|
Change in haemoglobin.
Time Frame: Week 1
|
To demonstrate early onset of efficacy of anakinra compared to placebo in Still's disease.
|
Week 1
|
Change in platelets count.
Time Frame: Week 1
|
To demonstrate early onset of efficacy of anakinra compared to placebo in Still's disease.
|
Week 1
|
Change in white blood cells count.
Time Frame: Week 1
|
To demonstrate early onset of efficacy of anakinra compared to placebo in Still's disease.
|
Week 1
|
Change in the number/proportion of patients reporting problems by dimension of EQ-5D-Y Proxy (4-7 years).
Time Frame: Week 2
|
To evaluate and compare the health status between anakinra treated patients and patients treated with placebo.
|
Week 2
|
Change in the number/proportion of patients reporting problems by dimension of EQ-5D-Y (8-15 years).
Time Frame: Week 2
|
To evaluate and compare the health status between anakinra treated patients and patients treated with placebo.
|
Week 2
|
Change in the number/proportion of patients reporting problems by dimension of EQ-5D-3L (≥ 16 years).
Time Frame: Week 2
|
To evaluate and compare the health status between anakinra treated patients and patients treated with placebo.
|
Week 2
|
Absence of fever during the 7 days preceding the visit.
Time Frame: Week 4 to Week 54
|
To evaluate efficacy of anakinra in Still's disease.
|
Week 4 to Week 54
|
Absence of rash during the 7 days preceding the visit.
Time Frame: Week 4 to Week 54
|
To evaluate efficacy of anakinra in Still's disease.
|
Week 4 to Week 54
|
ACR30 response with absence of fever during the 7 days preceding the visit.
Time Frame: Week 4 to Week 54
|
To evaluate efficacy of anakinra in Still's disease.
|
Week 4 to Week 54
|
ACR50 response with absence of fever during the 7 days preceding the visit.
Time Frame: Week 4 to Week 54
|
To evaluate efficacy of anakinra in Still's disease.
|
Week 4 to Week 54
|
ACR70 response with absence of fever during the 7 days preceding the visit.
Time Frame: Week 4 to Week 54
|
To evaluate efficacy of anakinra in Still's disease.
|
Week 4 to Week 54
|
ACR90 response with absence of fever during the 7 days preceding the visit.
Time Frame: Week 4 to Week 54
|
To evaluate efficacy of anakinra in Still's disease.
|
Week 4 to Week 54
|
Change in physician global assessment of disease activity (VAS).
Time Frame: Week 4 to Week 54
|
To evaluate efficacy of anakinra in Still's disease.
|
Week 4 to Week 54
|
Change in patient/parent global assessment of overall well-being (VAS).
Time Frame: Week 4 to Week 54
|
To evaluate efficacy of anakinra in Still's disease.
|
Week 4 to Week 54
|
Change in patient/parent global assessment of disease related pain (VAS).
Time Frame: Week 4 to Week 54
|
To evaluate efficacy of anakinra in Still's disease.
|
Week 4 to Week 54
|
Change in swelling joints count.
Time Frame: Week 4 to Week 54
|
To evaluate efficacy of anakinra in Still's disease.
|
Week 4 to Week 54
|
Change in tender joints count.
Time Frame: Week 4 to Week 54
|
To evaluate efficacy of anakinra in Still's disease.
|
Week 4 to Week 54
|
Change in CRP.
Time Frame: Week 4 to Week 54
|
To evaluate efficacy of anakinra in Still's disease.
|
Week 4 to Week 54
|
Change in ferritin.
Time Frame: Week 4 to Week 54
|
To evaluate efficacy of anakinra in Still's disease.
|
Week 4 to Week 54
|
Change in haemoglobin.
Time Frame: Week 4 to Week 54
|
To evaluate efficacy of anakinra in Still's disease.
|
Week 4 to Week 54
|
Change in platelets count.
Time Frame: Week 4 to Week 54
|
To evaluate efficacy of anakinra in Still's disease.
|
Week 4 to Week 54
|
Change in white blood cells count.
Time Frame: Week 4 to Week 54
|
To evaluate efficacy of anakinra in Still's disease.
|
Week 4 to Week 54
|
Occurrence of inactive disease.
Time Frame: Week 8 to Week 54
|
Proportion of patients who reach inactive disease.Inactive disease is defined as no joints with active arthritis, no fever, no rash, serositis, no hepatosplenomegaly, no generalized lymphadenopathy attributable to Still's disease, CRP level within normal limits, physician's global assessment of disease activity score below 10 mm on a 100 mm VAS, and a documented morning stiffness ≤15 min.
|
Week 8 to Week 54
|
Change in the number/proportion of patients reporting problems by dimension of EQ-5D-Y Proxy (4-7 years).
Time Frame: Week 4 to Week 54
|
To evaluate the health status in anakinra treated patients with Still's disease.
|
Week 4 to Week 54
|
Change in the number/proportion of patients reporting problems by dimension of EQ-5D-Y (8-15 years).
Time Frame: Week 4 to Week 54
|
To evaluate the health status in anakinra treated patients with Still's disease.
|
Week 4 to Week 54
|
Change in the number/proportion of patients reporting problems by dimension of EQ-5D-3L(≥ 16 years).
Time Frame: Week 4 to Week 54
|
To evaluate the health status in anakinra treated patients with Still's disease.
|
Week 4 to Week 54
|
ACR30 response with absence of fever during the 7 days preceding the study visits over time.
Time Frame: Week 2 to Week 54
|
To evaluate sustained efficacy of anakinra in patients responding to study drug.
|
Week 2 to Week 54
|
To evaluate the occurrence of study drug discontinuation in anakinra treated patients with Still's disease.
Time Frame: Day 1 to Week 54
|
|
Day 1 to Week 54
|
Time of initiation of glucocorticoids tapering.
Time Frame: Week 2 to Week 54
|
To evaluate glucocorticoids tapering in anakinra treated patients with Still's disease.
|
Week 2 to Week 54
|
Percentage decrease of glucocorticoids dose for patients tapering their glucocorticoids dose.
Time Frame: Week 2 to Week 54
|
To evaluate glucocorticoids tapering in anakinra treated patients with Still's disease.
|
Week 2 to Week 54
|
Discontinuation of glucocorticoids.
Time Frame: Week 2 to Week 54
|
To evaluate glucocorticoids tapering in anakinra treated patients with Still's disease.
|
Week 2 to Week 54
|
- Occurrence of adverse events (AEs) (serious adverse events [SAEs] and non-SAEs).
Time Frame: Baseline to Week 58
|
To evaluate the safety of anakinra in patients with Still ́s disease.
|
Baseline to Week 58
|
Occurrence of deaths
Time Frame: Baseline to Week 58
|
To evaluate the safety of anakinra in patients with Still ́s disease.
|
Baseline to Week 58
|
Occurrence of AEs leading to study drug discontinuation at all study visits.
Time Frame: Baseline to Week 58
|
To evaluate the safety of anakinra in patients with Still ́s disease.
|
Baseline to Week 58
|
Occurrence of vital signs changes from baseline, including blood pressure, heart rate, and body weight at all study visits up to Week 58 visit. Changes of height in patients younger than 19 years old.
Time Frame: Baseline to Week 58
|
To evaluate the safety of anakinra in patients with Still ́s disease.
|
Baseline to Week 58
|
Occurrence of laboratory safety assessments changes over time.
Time Frame: Baseline to Week 58
|
To evaluate the safety of anakinra in patients with Still ́s disease.
|
Baseline to Week 58
|
Occurrence of abnormal laboratory values.
Time Frame: Baseline to Week 58
|
To evaluate the safety of anakinra in patients with Still ́s disease.
|
Baseline to Week 58
|
To evaluate immunogenicity of anakinra in patients with Still's disease.
Time Frame: Baseline, Weeks 2, 4, 12, 34, 54 and 58
|
|
Baseline, Weeks 2, 4, 12, 34, 54 and 58
|
To evaluate the pharmacokinetic of anakinra in patients with Still's disease
Time Frame: Baseline, Weeks 1 and 2
|
Anakinra serum concentrations
|
Baseline, Weeks 1 and 2
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Masaaki Mori, MD, St. Marianna University Hospital
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- Sobi.ANAKIN-303
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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