Clinical trial NCT02296424: ß-SPECIFIC 4 Patients: Study of Pediatric EffiCacy and Safety wIth FIrst-line Use of Canakinumab
Official title: β-SPECIFIC 4 Patients: Study of Pediatric EffiCacy and Safety wIth FIrst-line Use of Canakinumab An Open-label Canakinumab (ACZ885) Dose Reduction or Dose Interval Prolongation Efficacy and Safety Study in Patients With Systemic Juvenile Idiopathic Arthritis (SJIA)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Systemic Juvenile Idiopathic Arthritis (SJIA)
Keywords: Juvenile Rheumatoid arthritis (JRA) chronic
systemic inflammatory disorder
painful joints
inflammation of the synovial membrane
auto-immune rheumatoid disease
reactive rheumatoid arthritis
Systemic Juvenile Rheumatoid arthritis (SJRA)
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2014-11-20
Enrollment: 182
Sex: ALL
Minimum age (years): 2
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A two-part open-label study that collected long-term efficacy, safety, and tolerability data from SJIA patients receiving canakinumab treatment who had inactive disease at the last visit in Study CACZ885G2301E1 (Cohort 1), and from SJIA patients who were canakinumab treatment-naïve and had active disease at the time of screening for this study (Cohort 2)
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to evaluate the efficacy observed with canakinumab dose reduction in a subgroup of patients in the extension study CACZ885G2301E1.

Detailed description: This two-part open-label study was to assess 2 different canakinumab taper regimens in patients with clinical remission (inactive disease for at least 24 continuous weeks) on canakinumab treatment without concomitant corticosteroids (CS) or methotrexate (MTX). The study was also to collect long term safety and tolerability data on SJIA patients treated with canakinumab.

Eligibility criteria: Inclusion Criteria:

Cohort 1:

• Patients who are receiving canakinumab treatment (4 mg/kg every 4 weeks) for Systemic Juvenile Idiopathic Arthritis (SJIA) and have inactive disease at the last visit in Study CACZ885G2301E1

Cohort 2:

* Confirmed diagnosis of SJIA as per International League Against Rheumatism (ILAR) definition that must have occurred at least 2 months prior to enrollment with an onset of disease \< 16 years of age.
* Active SJIA defined as having 2 or more of the following:
* Documented spiking, intermittent fever (body temperature \> 38°C) for at least 1 day within 1 week before first canakinumab dose;
* At least 2 joints with active arthritis
* C-reactive protein (CRP) \> 30 mg/L (normal range \< 10 mg/L)
* Rash due to SJIA
* Serositis
* Lymphadenopathy
* Hepatosplenomegaly
* Negative TB screen (QuantiFERON or, if required by local guidelines, Purified Protein Derivative).

Exclusion Criteria:

* With active or recurrent bacterial, fungal or viral infection at the time of enrollment, including patients with evidence of Human Immunodeficiency Virus (HIV) infection, Hepatitis B and Hepatitis C infection.
* With underlying metabolic, renal, hepatic, infectious or gastrointestinal conditions which in the opinion of the investigator immunocompromises the patient and /or places the patient at unacceptable risk for participation.
* With neutropenia (absolute neutrophil count \< 1500/mm3) at screening.

Primary outcomes:
measure: Number of Participants in Clinical Remission on Canakinumab Who Are Able to Remain at an Initial Reduced Canakinumab Dose or Prolonged Canakinumab Dose Interval.
timeFrame: baseline to 24 weeks
Secondary outcomes:
measure: Number and Percentage of Patients With Adverse Events as a Measure of Long-term Safety and Tolerability of Canakinumab - PART 1
timeFrame: During study parts I and II. The estimated study duration is not more than 216 weeks (with an average expected duration of 108 weeks).
measure: Number and Percentage of Patients With Adverse Events as a Measure of Long-term Safety and Tolerability of Canakinumab - PART 2
timeFrame: During study parts I and II, estimated study duration was not more than 216 weeks (with an average duration of 108 weeks).
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Novartis Investigative Site
state: California
city: Columbus
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Vienna
country: Austria
facility: Novartis Investigative Site
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Laeken
country: Belgium
facility: Novartis Investigative Site
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Curitiba
country: Brazil
facility: Novartis Investigative Site
state: PR
city: Rio de Janeiro
country: Brazil
facility: Novartis Investigative Site
state: RJ
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Vancouver
country: Canada
facility: Novartis Investigative Site
state: British Colombia
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Bron Cedex
country: France
facility: Novartis Investigative Site
city: Le Kremlin Bicetre
country: France
facility: Novartis Investigative Site
city: Paris cedex 15
country: France
facility: Novartis Investigative Site
city: Sankt Augustin
country: Germany
facility: Novartis Investigative Site
state: North Rhine-Westphalia
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Freiburg
country: Germany
facility: Novartis Investigative Site
city: Giessen
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Heidelberg
country: Germany
facility: Novartis Investigative Site
city: Tübingen
country: Germany
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Haifa
country: Israel
facility: Novartis Investigative Site
city: Jerusalem
country: Israel
facility: Novartis Investigative Site
city: Kfar Saba
country: Israel
facility: Novartis Investigative Site
city: Petach-Tikva
country: Israel
facility: Novartis Investigative Site
city: Ramat Gan
country: Israel
facility: Novartis Investigative Site
city: Bologna
country: Italy
facility: Novartis Investigative Site
state: BO
city: Genova
country: Italy
facility: Novartis Investigative Site
state: GE
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Napoli
country: Italy
facility: Novartis Investigative Site
city: Utrecht
country: Netherlands
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Saint-Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Malaga
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Esplugues de Llobregat
country: Spain
facility: Novartis Investigative Site
state: Barcelona
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Stockholm
country: Sweden
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
state: TUR
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Izmir
country: Turkey
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Quartier P, Alexeeva E, Constantin T, Chasnyk V, Wulffraat N, Palmblad K, Wouters C, I Brunner H, Marzan K, Schneider R, Horneff G, Martini A, Anton J, Wei X, Slade A, Ruperto N, Abrams K; Paediatric Rheumatology International Trials Organisation and the Pediatric Rheumatology Collaborative Study Group. Tapering Canakinumab Monotherapy in Patients With Systemic Juvenile Idiopathic Arthritis in Clinical Remission: Results From a Phase IIIb/IV Open-Label, Randomized Study. Arthritis Rheumatol. 2021 Feb;73(2):336-346. doi: 10.1002/art.41488. Epub 2020 Dec 11.