Single-dose Study to Assess Efficacy of Canakinumab (ACZ885) in Patients With Active Juvenile Idiopathic Arthritis (SJIA) (β-SPECIFIC 1)
28. februar 2017 opdateret af: 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.
Studieoversigt
Status
Afsluttet
Betingelser
Intervention / Behandling
Undersøgelsestype
Interventionel
Tilmelding (Faktiske)
84
Fase
- Fase 3
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
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Buenos Aires, Argentina
- Novartis Investigative Site
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Capital Federal, Argentina
- Novartis Investigative Site
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La Plata, Argentina
- Novartis Investigative Site
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Bruxelles, Belgien
- Novartis Investigative Site
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Gent, Belgien
- Novartis Investigative Site
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Laeken, Belgien
- Novartis Investigative Site
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Leuven, Belgien
- Novartis Investigative Site
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Curitiba, Brasilien
- Novartis Investigative Site
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Porto Alegre, Brasilien
- Novartis Investigative Site
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Rio de Janeiro, Brasilien
- Novartis Investigative Site
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Sao Paulo, Brasilien
- Novartis Investigative Site
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Calgary, Canada
- Novartis Investigative Site
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British Columbia
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Vancouver, British Columbia, Canada
- Novartis Investigative Site
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Nova Scotia
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Halifax, Nova Scotia, Canada
- Novartis Investigative Site
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Ontario
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Toronto, Ontario, Canada
- Novartis Investigative Site
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Quebec
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Montreal, Quebec, Canada
- Novartis Investigative Site
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Arhus N, Danmark
- Novartis Investigative Site
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Birmingham, Det Forenede Kongerige
- Novartis Investigative Site
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Liverpool, Det Forenede Kongerige
- Novartis Investigative Site
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London, Det Forenede Kongerige
- Novartis Investigative Site
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Manchester, Det Forenede Kongerige
- Novartis Investigative Site
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New Castle Upon Tyne, Det Forenede Kongerige
- Novartis Investigative Site
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Norwich, Det Forenede Kongerige
- Novartis Investigative Site
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Oxford, Det Forenede Kongerige
- Novartis Investigative Site
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Alabama
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Birmingham, Alabama, Forenede Stater, 35233
- University of Alabama at Birmingham
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Arkansas
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Little Rock, Arkansas, Forenede Stater, 72202
- Arkansas Children's Hospital Research Inst
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California
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Los Angeles, California, Forenede Stater, 90027
- Children's Hospital Los Angeles
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District of Columbia
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Washington, District of Columbia, Forenede Stater, 20010
- Children's National Medical Center
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Illinois
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Chicago, Illinois, Forenede Stater, 60637
- University Of Chicago Medical Center
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Kentucky
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Louisville, Kentucky, Forenede Stater, 40202
- University of Louisville
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Massachusetts
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Boston, Massachusetts, Forenede Stater, 02111
- Tufts Medical Center
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Boston, Massachusetts, Forenede Stater, 02111
- Tufts New England Medical Center-Dept. of Allergy
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New Jersey
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Livingston, New Jersey, Forenede Stater, 07039
- St. Barnabas Ambulatory Care Center
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Ohio
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Cincinnati, Ohio, Forenede Stater, 45229
- Children's Hospital Medical Center
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Cinncinati, Ohio, Forenede Stater, 45229
- Children's Hospital/Neurology
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Columbus, Ohio, Forenede Stater, 43205
- Nationwide Children's Hospital
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Oregon
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Portland, Oregon, Forenede Stater, 97227
- Legacy Emanuel Hospital
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Portland, Oregon, Forenede Stater, 97232
- Legacy Emanual Research
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Texas
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Austin, Texas, Forenede Stater, 78723
- Specially For Children
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Le Kremlin Bicetre, Frankrig
- Novartis Investigative Site
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Lyon, Frankrig
- Novartis Investigative Site
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Paris, Frankrig
- Novartis Investigative Site
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Strassbourg, Frankrig
- Novartis Investigative Site
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Thessaloniki, Grækenland
- Novartis Investigative Site
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Utrecht, Holland
- Novartis Investigative Site
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Haifa, Israel
- Novartis Investigative Site
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Kfar Saba, Israel
- Novartis Investigative Site
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Petach-Tikva, Israel
- Novartis Investigative Site
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Ramat Gan, Israel
- Novartis Investigative Site
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Rehovot, Israel
- Novartis Investigative Site
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Bologna, Italien
- Novartis Investigative Site
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Firenze, Italien
- Novartis Investigative Site
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Genova, Italien
- Novartis Investigative Site
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Milano, Italien
- Novartis Investigative Site
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Napoli, Italien
- Novartis Investigative Site
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Padova, Italien
- Novartis Investigative Site
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Rome, Italien
- Novartis Investigative Site
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Scafati, Italien
- Novartis Investigative Site
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Torino, Italien
- Novartis Investigative Site
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Ankara, Kalkun
- Novartis Investigative Site
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Istanbul, Kalkun
- Novartis Investigative Site
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Izmir, Kalkun
- Novartis Investigative Site
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Oslo, Norge
- Novartis Investigative Site
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Lima, Peru
- Novartis Investigative Site
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Warszawa, Polen
- Novartis Investigative Site
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Bern, Schweiz
- Novartis Investigative Site
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Lausanne, Schweiz
- Novartis Investigative Site
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Zurich, Schweiz
- Novartis Investigative Site
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Barcelona, Spanien
- Novartis Investigative Site
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Madrid, Spanien
- Novartis Investigative Site
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Valencia, Spanien
- Novartis Investigative Site
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Stockholm, Sverige
- Novartis Investigative Site
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Pretoria, Sydafrika
- Novartis Investigative Site
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Durban
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Berea, Durban, Sydafrika
- Novartis Investigative Site
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Mayville, Durban, Sydafrika
- Novartis Investigative Site
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Bad Bamstedt, Tyskland
- Novartis Investigative Site
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Berlin, Tyskland
- Novartis Investigative Site
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Bremen, Tyskland
- Novartis Investigative Site
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Dresden, Tyskland
- Novartis Investigative Site
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Freiburg, Tyskland
- Novartis Investigative Site
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Garmisch-Partenkirch, Tyskland
- Novartis Investigative Site
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Geissen, Tyskland
- Novartis Investigative Site
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Hamburg, Tyskland
- Novartis Investigative Site
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Hannover, Tyskland
- Novartis Investigative Site
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Krefeld, Tyskland
- Novartis Investigative Site
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Mainz, Tyskland
- Novartis Investigative Site
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Muenster, Tyskland
- Novartis Investigative Site
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Saint Augustin, Tyskland
- Novartis Investigative Site
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Stuttgart, Tyskland
- Novartis Investigative Site
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Tubingen, Tyskland
- Novartis Investigative Site
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Budapest, Ungarn
- Novartis Investigative Site
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Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
2 år til 19 år (Barn, Voksen)
Tager imod sunde frivillige
Ingen
Køn, der er berettiget til at studere
Alle
Beskrivelse
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
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Firedobbelt
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
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Eksperimentel: 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.
Andre navne:
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Placebo komparator: 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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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Percentage of Patients Who Meet the Adapted American College of Rheumatology (ACR) Pediatric 30 Criteria
Tidsramme: 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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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Percentage of Patients Achieving the Adapted ACR Pediatric 50 Criteria
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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)
Tidsramme: 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
Tidsramme: Baseline, Day 29
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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 29
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Percentage of Patients Who Had Body Temperature ≤ 38°C
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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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Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Publikationer og nyttige links
Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.
Generelle publikationer
- 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.
Hjælpsomme links
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart
1. juli 2009
Primær færdiggørelse (Faktiske)
1. december 2010
Studieafslutning (Faktiske)
1. januar 2011
Datoer for studieregistrering
Først indsendt
22. april 2009
Først indsendt, der opfyldte QC-kriterier
22. april 2009
Først opslået (Skøn)
23. april 2009
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
29. marts 2017
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
28. februar 2017
Sidst verificeret
1. februar 2017
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- CACZ885G2305
- EudraCT: 2008-005476-27
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .