Single-dose Study to Assess Efficacy of Canakinumab (ACZ885) in Patients With Active Juvenile Idiopathic Arthritis (SJIA) (β-SPECIFIC 1)
28 lutego 2017 zaktualizowane przez: 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.
Przegląd badań
Status
Zakończony
Interwencja / Leczenie
Typ studiów
Interwencyjne
Zapisy (Rzeczywisty)
84
Faza
- Faza 3
Kontakty i lokalizacje
Ta sekcja zawiera dane kontaktowe osób prowadzących badanie oraz informacje o tym, gdzie badanie jest przeprowadzane.
Lokalizacje studiów
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Pretoria, Afryka Południowa
- Novartis Investigative Site
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Durban
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Berea, Durban, Afryka Południowa
- Novartis Investigative Site
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Mayville, Durban, Afryka Południowa
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Buenos Aires, Argentyna
- Novartis Investigative Site
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Capital Federal, Argentyna
- Novartis Investigative Site
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La Plata, Argentyna
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Bruxelles, Belgia
- Novartis Investigative Site
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Gent, Belgia
- Novartis Investigative Site
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Laeken, Belgia
- Novartis Investigative Site
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Leuven, Belgia
- Novartis Investigative Site
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Curitiba, Brazylia
- Novartis Investigative Site
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Porto Alegre, Brazylia
- Novartis Investigative Site
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Rio de Janeiro, Brazylia
- Novartis Investigative Site
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Sao Paulo, Brazylia
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Arhus N, Dania
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Le Kremlin Bicetre, Francja
- Novartis Investigative Site
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Lyon, Francja
- Novartis Investigative Site
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Paris, Francja
- Novartis Investigative Site
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Strassbourg, Francja
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Thessaloniki, Grecja
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Barcelona, Hiszpania
- Novartis Investigative Site
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Madrid, Hiszpania
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Valencia, Hiszpania
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Utrecht, Holandia
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Ankara, Indyk
- Novartis Investigative Site
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Istanbul, Indyk
- Novartis Investigative Site
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Izmir, Indyk
- Novartis Investigative Site
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Haifa, Izrael
- Novartis Investigative Site
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Kfar Saba, Izrael
- Novartis Investigative Site
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Petach-Tikva, Izrael
- Novartis Investigative Site
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Ramat Gan, Izrael
- Novartis Investigative Site
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Rehovot, Izrael
- Novartis Investigative Site
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Calgary, Kanada
- Novartis Investigative Site
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British Columbia
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Vancouver, British Columbia, Kanada
- Novartis Investigative Site
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Nova Scotia
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Halifax, Nova Scotia, Kanada
- Novartis Investigative Site
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Ontario
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Toronto, Ontario, Kanada
- Novartis Investigative Site
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Quebec
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Montreal, Quebec, Kanada
- Novartis Investigative Site
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Bad Bamstedt, Niemcy
- Novartis Investigative Site
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Berlin, Niemcy
- Novartis Investigative Site
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Bremen, Niemcy
- Novartis Investigative Site
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Dresden, Niemcy
- Novartis Investigative Site
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Freiburg, Niemcy
- Novartis Investigative Site
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Garmisch-Partenkirch, Niemcy
- Novartis Investigative Site
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Geissen, Niemcy
- Novartis Investigative Site
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Hamburg, Niemcy
- Novartis Investigative Site
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Hannover, Niemcy
- Novartis Investigative Site
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Krefeld, Niemcy
- Novartis Investigative Site
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Mainz, Niemcy
- Novartis Investigative Site
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Muenster, Niemcy
- Novartis Investigative Site
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Saint Augustin, Niemcy
- Novartis Investigative Site
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Stuttgart, Niemcy
- Novartis Investigative Site
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Tubingen, Niemcy
- Novartis Investigative Site
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Oslo, Norwegia
- Novartis Investigative Site
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Lima, Peru
- Novartis Investigative Site
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Warszawa, Polska
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Alabama
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Birmingham, Alabama, Stany Zjednoczone, 35233
- University of Alabama at Birmingham
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Arkansas
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Little Rock, Arkansas, Stany Zjednoczone, 72202
- Arkansas Children's Hospital Research Inst
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California
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Los Angeles, California, Stany Zjednoczone, 90027
- Children's Hospital Los Angeles
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District of Columbia
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Washington, District of Columbia, Stany Zjednoczone, 20010
- Children's National Medical Center
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Illinois
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Chicago, Illinois, Stany Zjednoczone, 60637
- University of Chicago Medical Center
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Kentucky
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Louisville, Kentucky, Stany Zjednoczone, 40202
- University of Louisville
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Massachusetts
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Boston, Massachusetts, Stany Zjednoczone, 02111
- Tufts Medical Center
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Boston, Massachusetts, Stany Zjednoczone, 02111
- Tufts New England Medical Center-Dept. of Allergy
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New Jersey
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Livingston, New Jersey, Stany Zjednoczone, 07039
- St. Barnabas Ambulatory Care Center
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Ohio
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Cincinnati, Ohio, Stany Zjednoczone, 45229
- Children's Hospital Medical Center
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Cinncinati, Ohio, Stany Zjednoczone, 45229
- Children's Hospital/Neurology
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Columbus, Ohio, Stany Zjednoczone, 43205
- Nationwide Children's Hospital
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Oregon
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Portland, Oregon, Stany Zjednoczone, 97227
- Legacy Emanuel Hospital
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Portland, Oregon, Stany Zjednoczone, 97232
- Legacy Emanual Research
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Texas
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Austin, Texas, Stany Zjednoczone, 78723
- Specially For Children
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Bern, Szwajcaria
- Novartis Investigative Site
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Lausanne, Szwajcaria
- Novartis Investigative Site
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Zurich, Szwajcaria
- Novartis Investigative Site
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Stockholm, Szwecja
- Novartis Investigative Site
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Budapest, Węgry
- Novartis Investigative Site
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Bologna, Włochy
- Novartis Investigative Site
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Firenze, Włochy
- Novartis Investigative Site
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Genova, Włochy
- Novartis Investigative Site
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Milano, Włochy
- Novartis Investigative Site
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Napoli, Włochy
- Novartis Investigative Site
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Padova, Włochy
- Novartis Investigative Site
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Rome, Włochy
- Novartis Investigative Site
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Scafati, Włochy
- Novartis Investigative Site
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Torino, Włochy
- Novartis Investigative Site
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Birmingham, Zjednoczone Królestwo
- Novartis Investigative Site
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Liverpool, Zjednoczone Królestwo
- Novartis Investigative Site
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London, Zjednoczone Królestwo
- Novartis Investigative Site
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Manchester, Zjednoczone Królestwo
- Novartis Investigative Site
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New Castle Upon Tyne, Zjednoczone Królestwo
- Novartis Investigative Site
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Norwich, Zjednoczone Królestwo
- Novartis Investigative Site
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Oxford, Zjednoczone Królestwo
- Novartis Investigative Site
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Kryteria uczestnictwa
Badacze szukają osób, które pasują do określonego opisu, zwanego kryteriami kwalifikacyjnymi. Niektóre przykłady tych kryteriów to ogólny stan zdrowia danej osoby lub wcześniejsze leczenie.
Kryteria kwalifikacji
Wiek uprawniający do nauki
2 lata do 19 lat (Dziecko, Dorosły)
Akceptuje zdrowych ochotników
Nie
Płeć kwalifikująca się do nauki
Wszystko
Opis
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
Plan studiów
Ta sekcja zawiera szczegółowe informacje na temat planu badania, w tym sposób zaprojektowania badania i jego pomiary.
Jak projektuje się badanie?
Szczegóły projektu
- Główny cel: Leczenie
- Przydział: Randomizowane
- Model interwencyjny: Przydział równoległy
- Maskowanie: Poczwórny
Broń i interwencje
Grupa uczestników / Arm |
Interwencja / Leczenie |
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Eksperymentalny: 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.
Inne nazwy:
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Komparator placebo: 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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Co mierzy badanie?
Podstawowe miary wyniku
Miara wyniku |
Opis środka |
Ramy czasowe |
|---|---|---|
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Percentage of Patients Who Meet the Adapted American College of Rheumatology (ACR) Pediatric 30 Criteria
Ramy czasowe: 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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Miary wyników drugorzędnych
Miara wyniku |
Opis środka |
Ramy czasowe |
|---|---|---|
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Percentage of Patients Achieving the Adapted ACR Pediatric 50 Criteria
Ramy czasowe: Baseline, Day 15, Day 29
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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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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)
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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)
Ramy czasowe: Over 4 week study period (Baseline, Day 15, Day 29)
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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
Ramy czasowe: 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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Współpracownicy i badacze
Tutaj znajdziesz osoby i organizacje zaangażowane w to badanie.
Publikacje i pomocne linki
Osoba odpowiedzialna za wprowadzenie informacji o badaniu dobrowolnie udostępnia te publikacje. Mogą one dotyczyć wszystkiego, co jest związane z badaniem.
Publikacje ogólne
- 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.
Przydatne linki
Daty zapisu na studia
Daty te śledzą postęp w przesyłaniu rekordów badań i podsumowań wyników do ClinicalTrials.gov. Zapisy badań i zgłoszone wyniki są przeglądane przez National Library of Medicine (NLM), aby upewnić się, że spełniają określone standardy kontroli jakości, zanim zostaną opublikowane na publicznej stronie internetowej.
Główne daty studiów
Rozpoczęcie studiów
1 lipca 2009
Zakończenie podstawowe (Rzeczywisty)
1 grudnia 2010
Ukończenie studiów (Rzeczywisty)
1 stycznia 2011
Daty rejestracji na studia
Pierwszy przesłany
22 kwietnia 2009
Pierwszy przesłany, który spełnia kryteria kontroli jakości
22 kwietnia 2009
Pierwszy wysłany (Oszacować)
23 kwietnia 2009
Aktualizacje rekordów badań
Ostatnia wysłana aktualizacja (Rzeczywisty)
29 marca 2017
Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości
28 lutego 2017
Ostatnia weryfikacja
1 lutego 2017
Więcej informacji
Terminy związane z tym badaniem
Słowa kluczowe
Dodatkowe istotne warunki MeSH
Inne numery identyfikacyjne badania
- CACZ885G2305
- EudraCT: 2008-005476-27
Te informacje zostały pobrane bezpośrednio ze strony internetowej clinicaltrials.gov bez żadnych zmian. Jeśli chcesz zmienić, usunąć lub zaktualizować dane swojego badania, skontaktuj się z register@clinicaltrials.gov. Gdy tylko zmiana zostanie wprowadzona na stronie clinicaltrials.gov, zostanie ona automatycznie zaktualizowana również na naszej stronie internetowej .