Single-dose Study to Assess Efficacy of Canakinumab (ACZ885) in Patients With Active Juvenile Idiopathic Arthritis (SJIA) (β-SPECIFIC 1)
28. února 2017 aktualizováno: 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.
Přehled studie
Postavení
Ukončeno
Intervence / Léčba
Typ studie
Intervenční
Zápis (Aktuální)
84
Fáze
- Fáze 3
Kontakty a umístění
Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.
Studijní místa
-
-
-
Buenos Aires, Argentina
- Novartis Investigative Site
-
Capital Federal, Argentina
- Novartis Investigative Site
-
La Plata, Argentina
- Novartis Investigative Site
-
-
-
-
-
Bruxelles, Belgie
- Novartis Investigative Site
-
Gent, Belgie
- Novartis Investigative Site
-
Laeken, Belgie
- Novartis Investigative Site
-
Leuven, Belgie
- Novartis Investigative Site
-
-
-
-
-
Curitiba, Brazílie
- Novartis Investigative Site
-
Porto Alegre, Brazílie
- Novartis Investigative Site
-
Rio de Janeiro, Brazílie
- Novartis Investigative Site
-
Sao Paulo, Brazílie
- Novartis Investigative Site
-
-
-
-
-
Arhus N, Dánsko
- Novartis Investigative Site
-
-
-
-
-
Le Kremlin Bicetre, Francie
- Novartis Investigative Site
-
Lyon, Francie
- Novartis Investigative Site
-
Paris, Francie
- Novartis Investigative Site
-
Strassbourg, Francie
- Novartis Investigative Site
-
-
-
-
-
Utrecht, Holandsko
- Novartis Investigative Site
-
-
-
-
-
Bologna, Itálie
- Novartis Investigative Site
-
Firenze, Itálie
- Novartis Investigative Site
-
Genova, Itálie
- Novartis Investigative Site
-
Milano, Itálie
- Novartis Investigative Site
-
Napoli, Itálie
- Novartis Investigative Site
-
Padova, Itálie
- Novartis Investigative Site
-
Rome, Itálie
- Novartis Investigative Site
-
Scafati, Itálie
- Novartis Investigative Site
-
Torino, Itálie
- Novartis Investigative Site
-
-
-
-
-
Haifa, Izrael
- Novartis Investigative Site
-
Kfar Saba, Izrael
- Novartis Investigative Site
-
Petach-Tikva, Izrael
- Novartis Investigative Site
-
Ramat Gan, Izrael
- Novartis Investigative Site
-
Rehovot, Izrael
- Novartis Investigative Site
-
-
-
-
-
Pretoria, Jižní Afrika
- Novartis Investigative Site
-
-
Durban
-
Berea, Durban, Jižní Afrika
- Novartis Investigative Site
-
Mayville, Durban, Jižní Afrika
- Novartis Investigative Site
-
-
-
-
-
Calgary, Kanada
- Novartis Investigative Site
-
-
British Columbia
-
Vancouver, British Columbia, Kanada
- Novartis Investigative Site
-
-
Nova Scotia
-
Halifax, Nova Scotia, Kanada
- Novartis Investigative Site
-
-
Ontario
-
Toronto, Ontario, Kanada
- Novartis Investigative Site
-
-
Quebec
-
Montreal, Quebec, Kanada
- Novartis Investigative Site
-
-
-
-
-
Ankara, Krocan
- Novartis Investigative Site
-
Istanbul, Krocan
- Novartis Investigative Site
-
Izmir, Krocan
- Novartis Investigative Site
-
-
-
-
-
Budapest, Maďarsko
- Novartis Investigative Site
-
-
-
-
-
Oslo, Norsko
- Novartis Investigative Site
-
-
-
-
-
Bad Bamstedt, Německo
- Novartis Investigative Site
-
Berlin, Německo
- Novartis Investigative Site
-
Bremen, Německo
- Novartis Investigative Site
-
Dresden, Německo
- Novartis Investigative Site
-
Freiburg, Německo
- Novartis Investigative Site
-
Garmisch-Partenkirch, Německo
- Novartis Investigative Site
-
Geissen, Německo
- Novartis Investigative Site
-
Hamburg, Německo
- Novartis Investigative Site
-
Hannover, Německo
- Novartis Investigative Site
-
Krefeld, Německo
- Novartis Investigative Site
-
Mainz, Německo
- Novartis Investigative Site
-
Muenster, Německo
- Novartis Investigative Site
-
Saint Augustin, Německo
- Novartis Investigative Site
-
Stuttgart, Německo
- Novartis Investigative Site
-
Tubingen, Německo
- Novartis Investigative Site
-
-
-
-
-
Lima, Peru
- Novartis Investigative Site
-
-
-
-
-
Warszawa, Polsko
- Novartis Investigative Site
-
-
-
-
-
Birmingham, Spojené království
- Novartis Investigative Site
-
Liverpool, Spojené království
- Novartis Investigative Site
-
London, Spojené království
- Novartis Investigative Site
-
Manchester, Spojené království
- Novartis Investigative Site
-
New Castle Upon Tyne, Spojené království
- Novartis Investigative Site
-
Norwich, Spojené království
- Novartis Investigative Site
-
Oxford, Spojené království
- Novartis Investigative Site
-
-
-
-
Alabama
-
Birmingham, Alabama, Spojené státy, 35233
- University of Alabama at Birmingham
-
-
Arkansas
-
Little Rock, Arkansas, Spojené státy, 72202
- Arkansas Children's Hospital Research Inst
-
-
California
-
Los Angeles, California, Spojené státy, 90027
- Children's Hospital Los Angeles
-
-
District of Columbia
-
Washington, District of Columbia, Spojené státy, 20010
- Children's National Medical Center
-
-
Illinois
-
Chicago, Illinois, Spojené státy, 60637
- University Of Chicago Medical Center
-
-
Kentucky
-
Louisville, Kentucky, Spojené státy, 40202
- University of Louisville
-
-
Massachusetts
-
Boston, Massachusetts, Spojené státy, 02111
- Tufts Medical Center
-
Boston, Massachusetts, Spojené státy, 02111
- Tufts New England Medical Center-Dept. of Allergy
-
-
New Jersey
-
Livingston, New Jersey, Spojené státy, 07039
- St. Barnabas Ambulatory Care Center
-
-
Ohio
-
Cincinnati, Ohio, Spojené státy, 45229
- Children's Hospital Medical Center
-
Cinncinati, Ohio, Spojené státy, 45229
- Children's Hospital/Neurology
-
Columbus, Ohio, Spojené státy, 43205
- Nationwide Children's Hospital
-
-
Oregon
-
Portland, Oregon, Spojené státy, 97227
- Legacy Emanuel Hospital
-
Portland, Oregon, Spojené státy, 97232
- Legacy Emanual Research
-
-
Texas
-
Austin, Texas, Spojené státy, 78723
- Specially For Children
-
-
-
-
-
Thessaloniki, Řecko
- Novartis Investigative Site
-
-
-
-
-
Barcelona, Španělsko
- Novartis Investigative Site
-
Madrid, Španělsko
- Novartis Investigative Site
-
Valencia, Španělsko
- Novartis Investigative Site
-
-
-
-
-
Stockholm, Švédsko
- Novartis Investigative Site
-
-
-
-
-
Bern, Švýcarsko
- Novartis Investigative Site
-
Lausanne, Švýcarsko
- Novartis Investigative Site
-
Zurich, Švýcarsko
- Novartis Investigative Site
-
-
Kritéria účasti
Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.
Kritéria způsobilosti
Věk způsobilý ke studiu
2 roky až 19 let (Dítě, Dospělý)
Přijímá zdravé dobrovolníky
Ne
Pohlaví způsobilá ke studiu
Všechno
Popis
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
Studijní plán
Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Čtyřnásobek
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
|
Experimentální: 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.
|
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.
Ostatní jména:
|
|
Komparátor placeba: Placebo
Patients received a single dose matching placebo of canakinumab on day 1.
|
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.
|
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Percentage of Patients Who Meet the Adapted American College of Rheumatology (ACR) Pediatric 30 Criteria
Časové okno: Baseline, Day 15, Day 29
|
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)
|
Baseline, Day 15, Day 29
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Percentage of Patients Achieving the Adapted ACR Pediatric 50 Criteria
Časové okno: 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)
|
Baseline, Day 15, Day 29
|
|
Percentage of Patients Achieving the Adapted ACR Pediatric 70
Časové okno: Baseline, Day 15, Day 29
|
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)
|
Baseline, Day 15, Day 29
|
|
Percentage of Patients Achieving the Adapted ACR Pediatric 90
Časové okno: Baseline, Day 15, Day 29
|
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)
|
Baseline, Day 15, Day 29
|
|
Percentage of Patients Achieving the Adapted ACR Pediatric 100
Časové okno: baseline, Day 15, Day 29
|
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
|
baseline, Day 15, Day 29
|
|
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)
Časové okno: Baseline, Day 15
|
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.
|
Baseline, Day 15
|
|
Change in Patient's Pain Intensity as Assessed on a 100-mm Visual Analog Scale (VAS) as Part of CHAQ
Časové okno: 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.
|
Baseline, Day 29
|
|
Percentage of Patients Who Had Body Temperature ≤ 38°C
Časové okno: Day 3
|
Body temperature was derived from vital signs evaluation.
No conversion of body temperature was performed, no matter how it was measured.
|
Day 3
|
|
Change in Health-related Quality of Life (HRQoL)Over Time by Use of the Child Health Questionnaire - Parent Form (CHQ-PF50)
Časové okno: 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.
|
Over 4 week study period (Baseline, Day 15, Day 29)
|
|
Change in Disability Score Over Time by Use of the CHAQ
Časové okno: At 4 week study period
|
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.
|
At 4 week study period
|
Spolupracovníci a vyšetřovatelé
Zde najdete lidi a organizace zapojené do této studie.
Publikace a užitečné odkazy
Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.
Obecné publikace
- 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.
Užitečné odkazy
Termíny studijních záznamů
Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.
Hlavní termíny studia
Začátek studia
1. července 2009
Primární dokončení (Aktuální)
1. prosince 2010
Dokončení studie (Aktuální)
1. ledna 2011
Termíny zápisu do studia
První předloženo
22. dubna 2009
První předloženo, které splnilo kritéria kontroly kvality
22. dubna 2009
První zveřejněno (Odhad)
23. dubna 2009
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
29. března 2017
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
28. února 2017
Naposledy ověřeno
1. února 2017
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
Další identifikační čísla studie
- CACZ885G2305
- EudraCT: 2008-005476-27
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .