Single-dose Study to Assess Efficacy of Canakinumab (ACZ885) in Patients With Active Juvenile Idiopathic Arthritis (SJIA) (β-SPECIFIC 1)
2017年2月28日 更新者：Novartis Pharmaceuticals
A Randomized, Double-blind, Placebo Controlled, Single-dose Study to Assess the Initial Efficacy of Canakinumab (ACZ885) With Respect to the Adapted ACR Pediatric 30 Criteria in Patients With Systemic Juvenile Idiopathic Arthritis (SJIA) and Active Systemic Manifestations
This study assessed the initial efficacy and safety of canakinumab over a 4 week period in patients with systemic juvenile idiopathic arthritis (SJIA) having a flare.
Response to treatment will be according to the adapted American College of Rheumatology(ACR)Pediatric 30 criteria at Day 15.
調査の概要
研究の種類
介入
入学 (実際)
84
段階
- フェーズ 3
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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Alabama
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Birmingham、Alabama、アメリカ、35233
- University of Alabama at Birmingham
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Arkansas
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Little Rock、Arkansas、アメリカ、72202
- Arkansas Children's Hospital Research Inst
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California
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Los Angeles、California、アメリカ、90027
- Children's Hospital Los Angeles
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District of Columbia
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Washington、District of Columbia、アメリカ、20010
- Children's National Medical Center
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Illinois
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Chicago、Illinois、アメリカ、60637
- University of Chicago Medical Center
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Kentucky
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Louisville、Kentucky、アメリカ、40202
- University of Louisville
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Massachusetts
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Boston、Massachusetts、アメリカ、02111
- Tufts Medical Center
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Boston、Massachusetts、アメリカ、02111
- Tufts New England Medical Center-Dept. of Allergy
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New Jersey
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Livingston、New Jersey、アメリカ、07039
- St. Barnabas Ambulatory Care Center
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Ohio
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Cincinnati、Ohio、アメリカ、45229
- Children's Hospital Medical Center
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Cinncinati、Ohio、アメリカ、45229
- Children's Hospital/Neurology
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Columbus、Ohio、アメリカ、43205
- Nationwide Children's Hospital
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Oregon
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Portland、Oregon、アメリカ、97227
- Legacy Emanuel Hospital
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Portland、Oregon、アメリカ、97232
- Legacy Emanual Research
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Texas
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Austin、Texas、アメリカ、78723
- Specially For Children
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Buenos Aires、アルゼンチン
- Novartis Investigative Site
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Capital Federal、アルゼンチン
- Novartis Investigative Site
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La Plata、アルゼンチン
- Novartis Investigative Site
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Birmingham、イギリス
- Novartis Investigative Site
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Liverpool、イギリス
- Novartis Investigative Site
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London、イギリス
- Novartis Investigative Site
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Manchester、イギリス
- Novartis Investigative Site
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New Castle Upon Tyne、イギリス
- Novartis Investigative Site
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Norwich、イギリス
- Novartis Investigative Site
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Oxford、イギリス
- Novartis Investigative Site
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Haifa、イスラエル
- Novartis Investigative Site
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Kfar Saba、イスラエル
- Novartis Investigative Site
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Petach-Tikva、イスラエル
- Novartis Investigative Site
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Ramat Gan、イスラエル
- Novartis Investigative Site
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Rehovot、イスラエル
- Novartis Investigative Site
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Bologna、イタリア
- Novartis Investigative Site
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Firenze、イタリア
- Novartis Investigative Site
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Genova、イタリア
- Novartis Investigative Site
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Milano、イタリア
- Novartis Investigative Site
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Napoli、イタリア
- Novartis Investigative Site
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Padova、イタリア
- Novartis Investigative Site
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Rome、イタリア
- Novartis Investigative Site
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Scafati、イタリア
- Novartis Investigative Site
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Torino、イタリア
- Novartis Investigative Site
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Utrecht、オランダ
- Novartis Investigative Site
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Calgary、カナダ
- Novartis Investigative Site
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British Columbia
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Vancouver、British Columbia、カナダ
- Novartis Investigative Site
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Nova Scotia
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Halifax、Nova Scotia、カナダ
- Novartis Investigative Site
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Ontario
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Toronto、Ontario、カナダ
- Novartis Investigative Site
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Quebec
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Montreal、Quebec、カナダ
- Novartis Investigative Site
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Thessaloniki、ギリシャ
- Novartis Investigative Site
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Bern、スイス
- Novartis Investigative Site
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Lausanne、スイス
- Novartis Investigative Site
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Zurich、スイス
- Novartis Investigative Site
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Stockholm、スウェーデン
- Novartis Investigative Site
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Barcelona、スペイン
- Novartis Investigative Site
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Madrid、スペイン
- Novartis Investigative Site
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Valencia、スペイン
- Novartis Investigative Site
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Arhus N、デンマーク
- Novartis Investigative Site
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Bad Bamstedt、ドイツ
- Novartis Investigative Site
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Berlin、ドイツ
- Novartis Investigative Site
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Bremen、ドイツ
- Novartis Investigative Site
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Dresden、ドイツ
- Novartis Investigative Site
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Freiburg、ドイツ
- Novartis Investigative Site
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Garmisch-Partenkirch、ドイツ
- Novartis Investigative Site
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Geissen、ドイツ
- Novartis Investigative Site
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Hamburg、ドイツ
- Novartis Investigative Site
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Hannover、ドイツ
- Novartis Investigative Site
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Krefeld、ドイツ
- Novartis Investigative Site
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Mainz、ドイツ
- Novartis Investigative Site
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Muenster、ドイツ
- Novartis Investigative Site
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Saint Augustin、ドイツ
- Novartis Investigative Site
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Stuttgart、ドイツ
- Novartis Investigative Site
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Tubingen、ドイツ
- Novartis Investigative Site
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Oslo、ノルウェー
- Novartis Investigative Site
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Budapest、ハンガリー
- Novartis Investigative Site
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Le Kremlin Bicetre、フランス
- Novartis Investigative Site
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Lyon、フランス
- Novartis Investigative Site
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Paris、フランス
- Novartis Investigative Site
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Strassbourg、フランス
- Novartis Investigative Site
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Curitiba、ブラジル
- Novartis Investigative Site
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Porto Alegre、ブラジル
- Novartis Investigative Site
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Rio de Janeiro、ブラジル
- Novartis Investigative Site
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Sao Paulo、ブラジル
- Novartis Investigative Site
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Bruxelles、ベルギー
- Novartis Investigative Site
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Gent、ベルギー
- Novartis Investigative Site
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Laeken、ベルギー
- Novartis Investigative Site
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Leuven、ベルギー
- Novartis Investigative Site
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Lima、ペルー
- Novartis Investigative Site
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Warszawa、ポーランド
- Novartis Investigative Site
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Ankara、七面鳥
- Novartis Investigative Site
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Istanbul、七面鳥
- Novartis Investigative Site
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Izmir、七面鳥
- Novartis Investigative Site
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Pretoria、南アフリカ
- Novartis Investigative Site
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Durban
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Berea、Durban、南アフリカ
- Novartis Investigative Site
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Mayville、Durban、南アフリカ
- Novartis Investigative Site
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
2年～19年 (子、大人)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
Inclusion Criteria:
Confirmed diagnosis of systemic juvenile idiopathic arthritis as per ILAR definition that must have occurred at least 2 months prior to enrollment with onset of disease < 16 years of age:
- Arthritis in one or more joints with or preceded by fever of at least 2 weeks duration that is documented to be daily/quotidian for at least 3 days and accompanied by one or more of the following:
- evanescent nonfixed erythematous rash,
- generalized lymph node enlargement,
- hepatomegaly and/ or splenomegaly,
- serositis
- Parent's or legal guardian's written informed consent and child's assent, if appropriate, or patient's informed consent for ≥ 18 years of age
- Male and female patients aged ≥ 2 to < 20 years of age
Active disease at the time of enrollment defined as follows:
- At least 2 joints with active arthritis
- Documented spiking, intermittent fever (body temperature > 38°C) for at least 1 day during the screening period within 1 week before first canakinumab/placebo dose
- C-reactive protein (CRP) > 30 mg/L (normal range < 10 mg/L)
- Naïve to canakinumab
- Other protocol defined inclusion criteria may apply
Exclusion Criteria:
Patients who fulfilled one or more of the following criteria were not eligible for inclusion in this study:
- Pregnant or nursing (lactating) female patients
- Female patients having reached sexual maturity unless their career, lifestyle, or sexual orientation precluded intercourse with a male partner and/or they were using an acceptable method of contraception
- History of hypersensitivity to study drug or to biologics.
- Diagnosis of active macrophage-activation syndrome (MAS) (Ravelli, Magni-Manzoni and Pistorio 2005) within the last 6 months
- With active or recurrent bacterial, fungal or viral infection, including patients with evidence of human immunodeficiency virus (HIV) infection, hepatitis B or hepatitis C infection
- Other protocol defined exclusion criteria may apply
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：Canakinumab
Patients received a single dose of subcutaneous(sc) injection of canakinumab (4 mg/kg) on Day 1. Maximal total single dose of canakinumab allowed was 300 mg.
Any patient who required a dose greater than 150 mg (patients>37.5
kg) received two sc injections.
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Canakinumab was supplied in individual 6 mL glass vials each containing 150 mg canakinumab powder as a lyophilized cake.
Each reconstituted vial provided 150mg of canakinumab per 1 mL.
他の名前：
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プラセボコンパレーター：Placebo
Patients received a single dose matching placebo of canakinumab on day 1.
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Placebo was provided in individual 6 mL glass vials each containing 150 mg placebo powder matching canakinumab as a lyophilized cake.
Each reconstitued vial provided 150mg of placebo per 1 mL.
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Percentage of Patients Who Meet the Adapted American College of Rheumatology (ACR) Pediatric 30 Criteria
時間枠：Baseline, Day 15, Day 29
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Adapted ACR Pediatric 30 criteria determined responders (improved from baseline of at least 30% in at least 3 response variables 1-6 and no intermittent fever in preceding week [variable 7], with no more than one variable 1-6 worsening > 30% ) 1. Physician's Global Assessment of disease activity: 0-100 mm VAS 2.Parent/Patient's Global Assessment of Patient's overall wellbeing: 0-100mmVAS in Child Health Assessment Questionnaire (CHAQ) 3. Functional ability: CHAQ 4.Number of joints with active arthritis 5. Number of joints with limited of motion 6. Laboratory measure of inflammation CRP (mg/L)
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Baseline, Day 15, Day 29
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Percentage of Patients Achieving the Adapted ACR Pediatric 50 Criteria
時間枠：Baseline, Day 15, Day 29
|
Adapted ACR Pediatric 50 criteria determined responders (improved from baseline of at least 50% in at least 3 response variables 1-6 and no intermittent fever in preceding week [variable 7], with no more than one variable 1-6 worsening > 30%) 1. Physician's Global Assessment of disease activity: 0-100 mm VAS 2. Parent/Patient's Global Assessment of Patient's overall wellbeing: 0-100mmVAS in Child Health Assessment Questionnaire (CHAQ) 3. Functional ability: CHAQ 4. Number of joints with active arthritis 5. Number of joints with limited of motion 6. Laboratory measure of inflammation CRP (mg/L)
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Baseline, Day 15, Day 29
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Percentage of Patients Achieving the Adapted ACR Pediatric 70
時間枠：Baseline, Day 15, Day 29
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Adapted ACR Pediatric 70 criteria determined responders (improved from baseline of at least 70% in at least 3 response variables 1-6 and no intermittent fever in preceding week [variable 7], with no more than one variable 1-6 worsening > 30% ) 1. Physician's Global Assessment of disease activity: 0-100 mm VAS 2. Parent/Patient's Global Assessment of Patient's overall wellbeing: 0-100mmVAS in Child Health Assessment Questionnaire (CHAQ) 3. Functional ability: CHAQ 4. Number of joints with active arthritis 5. Number of joints with limited of motion 6. Laboratory measure of inflammation CRP(mg/L)
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Baseline, Day 15, Day 29
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Percentage of Patients Achieving the Adapted ACR Pediatric 90
時間枠：Baseline, Day 15, Day 29
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Adapted ACR Pediatric 90 criteria determined responders (improved from baseline of at least 90% in at least 3 response variables 1-6 and no intermittent fever in preceding week [variable 7], with no more than one variable 1-6 worsening > 30% ) 1. Physician's Global Assessment of disease activity: 0-100 mm VAS 2. Parent/Patient's Global Assessment of Patient's overall wellbeing: 0-100mmVAS in Child Health Assessment Questionnaire (CHAQ) 3. Functional ability: CHAQ 4. Number of joints with active arthritis 5. Number of joints with limited of motion 6. Laboratory measure of inflammation CRP(mg/L)
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Baseline, Day 15, Day 29
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Percentage of Patients Achieving the Adapted ACR Pediatric 100
時間枠：baseline, Day 15, Day 29
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Adapted ACR Pediatric 100 criteria determined responders (ie improved from baseline of at least 100% in at least 3 response variables 1-6 and no intermittent fever in preceding week [variable 7], with no more than one variable 1-6 worsening > 30% ) 1. Physician's Global Assessment of disease activity: 0-100 mm VAS 2. Parent/Patient's Global Assessment of Patient's overall wellbeing: 0-100mmVAS in Child Health Assessment Questionnaire (CHAQ) 3. Functional ability: CHAQ 4. Number of joints with active arthritis 5. Number of joints with limited of motion 6. Laboratory measure of inflammation
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baseline, Day 15, Day 29
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Change in Patient's Pain Intensity as Assessed on a 100-mm Visual Analog Scale (VAS)as Part of the Childhood Health Assessment Questionnaire(CHAQ)
時間枠：Baseline, Day 15
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CHAQ assessed physical ability and functional status of patients as well as quality of life.
The disability dimension consisted of 20 multiple choice items about difficulty in doing eight common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities.
Four response categories range from 'without any difficulty' (0) to 'unable to do' (3).
The parent's or patient's pain assessment was on VAS that was part of CHAQ.
The VAS scale ranges from no pain (0 mm) to very severe pain (100 mm).
Negative change indicates improvement.
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Baseline, Day 15
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Change in Patient's Pain Intensity as Assessed on a 100-mm Visual Analog Scale (VAS) as Part of CHAQ
時間枠：Baseline, Day 29
|
CHAQ, assessed physical ability and functional status of patients as well as quality of life.
The disability dimension consisted of 20 multiple choice items about difficulty in doing eight common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities.
Four response categories range from 'without any difficulty'(0) to 'unable to do' (3).
The parent's or patient's pain assessment was on VAS that was part of CHAQ.
The VAS scale ranges from no pain (0 mm) to very severe pain (100 mm).
Negative change indicates improvement.
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Baseline, Day 29
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Percentage of Patients Who Had Body Temperature ≤ 38°C
時間枠：Day 3
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Body temperature was derived from vital signs evaluation.
No conversion of body temperature was performed, no matter how it was measured.
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Day 3
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Change in Health-related Quality of Life (HRQoL)Over Time by Use of the Child Health Questionnaire - Parent Form (CHQ-PF50)
時間枠：Over 4 week study period (Baseline, Day 15, Day 29)
|
CHQ-PF50 measures HRQoL in children 5-18 years old from parent's perspective.
Questionnaire completed by parent without input from patient.
Total score ranges from 0-100.
Increases in scores represent improved well-being in subjects as assessed by their parents.
Mixed linear model on change from baseline in CHQ-PF50 score with treatment group, stratification factors, day of assessment and interaction between group and day as covariates.
Covariance analysis used a repeated measures approach, so all timepoints over time were taken into account.
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Over 4 week study period (Baseline, Day 15, Day 29)
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Change in Disability Score Over Time by Use of the CHAQ
時間枠：At 4 week study period
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The disability dimension of CHAQ consisted of 20 multiple choice items about difficulty in doing eight common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities.
Four response categories range from 'without any difficulty'(0) to 'unable to do' (3).
Mixed linear model on change from baseline in CHAQ score included treatment group, stratification factors, day of assessment and interaction between group and day as covariates.
Negative change indicates improvement.
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At 4 week study period
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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
一般刊行物
- Ruperto N, Brunner HI, Quartier P, Constantin T, Wulffraat NM, Horneff G, Kasapcopur O, Schneider R, Anton J, Barash J, Berner R, Corona F, Cuttica R, Fouillet-Desjonqueres M, Fischbach M, Foster HE, Foell D, Radominski SC, Ramanan AV, Trauzeddel R, Unsal E, Levy J, Vritzali E, Martini A, Lovell DJ; Paediatric Rheumatology International Trials Organisation (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG). Canakinumab in patients with systemic juvenile idiopathic arthritis and active systemic features: results from the 5-year long-term extension of the phase III pivotal trials. Ann Rheum Dis. 2018 Dec;77(12):1710-1719. doi: 10.1136/annrheumdis-2018-213150. Epub 2018 Sep 29.
- Brachat AH, Grom AA, Wulffraat N, Brunner HI, Quartier P, Brik R, McCann L, Ozdogan H, Rutkowska-Sak L, Schneider R, Gerloni V, Harel L, Terreri M, Houghton K, Joos R, Kingsbury D, Lopez-Benitez JM, Bek S, Schumacher M, Valentin MA, Gram H, Abrams K, Martini A, Lovell DJ, Nirmala NR, Ruperto N; Pediatric Rheumatology International Trials Organization (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG). Early changes in gene expression and inflammatory proteins in systemic juvenile idiopathic arthritis patients on canakinumab therapy. Arthritis Res Ther. 2017 Jan 23;19(1):13. doi: 10.1186/s13075-016-1212-x.
- Ruperto N, Brunner HI, Quartier P, Constantin T, Wulffraat N, Horneff G, Brik R, McCann L, Kasapcopur O, Rutkowska-Sak L, Schneider R, Berkun Y, Calvo I, Erguven M, Goffin L, Hofer M, Kallinich T, Oliveira SK, Uziel Y, Viola S, Nistala K, Wouters C, Cimaz R, Ferrandiz MA, Flato B, Gamir ML, Kone-Paut I, Grom A, Magnusson B, Ozen S, Sztajnbok F, Lheritier K, Abrams K, Kim D, Martini A, Lovell DJ; PRINTO; PRCSG. Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis. N Engl J Med. 2012 Dec 20;367(25):2396-406. doi: 10.1056/NEJMoa1205099.
- Grom AA, Ilowite NT, Pascual V, Brunner HI, Martini A, Lovell D, Ruperto N; Paediatric Rheumatology International Trials Organisation and the Pediatric Rheumatology Collaborative Study Group; Leon K, Lheritier K, Abrams K. Rate and Clinical Presentation of Macrophage Activation Syndrome in Patients With Systemic Juvenile Idiopathic Arthritis Treated With Canakinumab. Arthritis Rheumatol. 2016 Jan;68(1):218-28. doi: 10.1002/art.39407.
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始
2009年7月1日
一次修了 (実際)
2010年12月1日
研究の完了 (実際)
2011年1月1日
試験登録日
最初に提出
2009年4月22日
QC基準を満たした最初の提出物
2009年4月22日
最初の投稿 (見積もり)
2009年4月23日
学習記録の更新
投稿された最後の更新 (実際)
2017年3月29日
QC基準を満たした最後の更新が送信されました
2017年2月28日
最終確認日
2017年2月1日
詳しくは
本研究に関する用語
キーワード
その他の研究ID番号
- CACZ885G2305
- EudraCT: 2008-005476-27
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。