Back to resultsß-SPECIFIC 4 Patients: Study of Pediatric EffiCacy and Safety wIth FIrst-line Use of Canakinumab (ß-SPECIFIC 4)
Primary Purpose
Systemic Juvenile Idiopathic Arthritis (SJIA)
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
ACZ885 150 mg (Canakinumab)
Sponsored by
About this trial
This is an interventional treatment trial for Systemic Juvenile Idiopathic Arthritis (SJIA) focused on measuring 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)
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.
Sites / Locations
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Canakinumab Dose Reduction
Canakinumab Dose Interval Prolongation
Arm Description
All patients received canakinumab 4mg/kg (300 mg max) every 4 weeks in Part I of the study. Patients eligible for Part II of the study were randomized to one of two treatment arms. This is Treatment Arm 1 in Part II of the study: Canakinumab was administered at a reduced dose (2 mg/kg every 4 weeks). If the patient continued to maintain inactive disease for 24 additional weeks, canakinumab was administered at 1mg/kg every 4 weeks. If the patient continued to maintain inactive disease for another 24 additional weeks, canakinumab treatment was discontinued.
All participants received canakinumab 4mg/kg (300 mg max) every 4 weeks in Part I of the study. Patients eligible for Part II of the study were randomized to one of two treatment arms. This is Treatment Arm 2 in Part II of the study: Canakinumab dose interval was prolonged to a regimen of 4mg/kg every 8 weeks. If the patient continued to be stable with inactive disease for 24 additional weeks, canakinumab dose interval was prolonged to a regimen of 4mg/kg every 12 weeks. If the patient was clinically stable with inactive disease for another 24 additional weeks, canakinumab treatment was discontinued.
Outcomes
Primary Outcome Measures
Number of Participants in Clinical Remission on Canakinumab Who Are Able to Remain at an Initial Reduced Canakinumab Dose or Prolonged Canakinumab Dose Interval.
The primary efficacy variable for Part II was the proportion of patients in clinical remission on canakinumab 4 mg/kg (+/- concomitant NSAID only) who were able to remain on a reduced dose or on prolonged dose interval for at least 24 consecutive weeks. As the primary objective was to show statistically significance in at least one of canakinumab treatment arms (reduced dose and prolonged dose interval arms) in Part II then the Type I error rate 5% was controlled and split to 2.5%. Clinical remission per protocol is defined as the maintenance of inactive disease for at least 6 months (24consecutive weeks) while on therapy. The primary analysis considered both inactive disease status and the patient dose step duration.
In the event the inactive disease status was missing, yet the patient remained at the same dose level through the next visit with the same disease status, it was concluded that inactive disease was maintained during this time period and was carried forward.
Secondary Outcome Measures
Number and Percentage of Patients With Adverse Events as a Measure of Long-term Safety and Tolerability of Canakinumab - PART 1
AEs, Deaths, other serious adverse events or discontinuations due to AE, Part I (Safety set)
Number and Percentage of Patients With Adverse Events as a Measure of Long-term Safety and Tolerability of Canakinumab - PART 2
AEs, Deaths, other serious adverse events or discontinuations due to AE, Part II (Safety set)
Full Information
NCT ID
NCT02296424
First Posted
October 10, 2014
Last Updated
June 17, 2019
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT02296424
Brief Title
ß-SPECIFIC 4 Patients: Study of Pediatric EffiCacy and Safety wIth FIrst-line Use of Canakinumab
Acronym
ß-SPECIFIC 4
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
2. Study Status
Record Verification Date
June 2019
Overall Recruitment Status
Completed
Study Start Date
November 17, 2014 (Actual)
Primary Completion Date
October 14, 2016 (Actual)
Study Completion Date
September 25, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
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)
Masking
None (Open Label)
Masking Description
No blinding was required in this open-label study
Allocation
Non-Randomized
Enrollment
182 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Canakinumab Dose Reduction
Arm Type
Experimental
Arm Description
All patients received canakinumab 4mg/kg (300 mg max) every 4 weeks in Part I of the study. Patients eligible for Part II of the study were randomized to one of two treatment arms. This is Treatment Arm 1 in Part II of the study: Canakinumab was administered at a reduced dose (2 mg/kg every 4 weeks). If the patient continued to maintain inactive disease for 24 additional weeks, canakinumab was administered at 1mg/kg every 4 weeks. If the patient continued to maintain inactive disease for another 24 additional weeks, canakinumab treatment was discontinued.
Arm Title
Canakinumab Dose Interval Prolongation
Arm Type
Experimental
Arm Description
All participants received canakinumab 4mg/kg (300 mg max) every 4 weeks in Part I of the study. Patients eligible for Part II of the study were randomized to one of two treatment arms. This is Treatment Arm 2 in Part II of the study: Canakinumab dose interval was prolonged to a regimen of 4mg/kg every 8 weeks. If the patient continued to be stable with inactive disease for 24 additional weeks, canakinumab dose interval was prolonged to a regimen of 4mg/kg every 12 weeks. If the patient was clinically stable with inactive disease for another 24 additional weeks, canakinumab treatment was discontinued.
Intervention Type
Drug
Intervention Name(s)
ACZ885 150 mg (Canakinumab)
Other Intervention Name(s)
ACZ885 150 mg
Intervention Description
Active canakinumab in individual 2 mL glass vials, each containing 150 mg canakinumab liquid in vial.
Primary Outcome Measure Information:
Title
Number of Participants in Clinical Remission on Canakinumab Who Are Able to Remain at an Initial Reduced Canakinumab Dose or Prolonged Canakinumab Dose Interval.
Description
The primary efficacy variable for Part II was the proportion of patients in clinical remission on canakinumab 4 mg/kg (+/- concomitant NSAID only) who were able to remain on a reduced dose or on prolonged dose interval for at least 24 consecutive weeks. As the primary objective was to show statistically significance in at least one of canakinumab treatment arms (reduced dose and prolonged dose interval arms) in Part II then the Type I error rate 5% was controlled and split to 2.5%. Clinical remission per protocol is defined as the maintenance of inactive disease for at least 6 months (24consecutive weeks) while on therapy. The primary analysis considered both inactive disease status and the patient dose step duration.
In the event the inactive disease status was missing, yet the patient remained at the same dose level through the next visit with the same disease status, it was concluded that inactive disease was maintained during this time period and was carried forward.
Time Frame
baseline to 24 weeks
Secondary Outcome Measure Information:
Title
Number and Percentage of Patients With Adverse Events as a Measure of Long-term Safety and Tolerability of Canakinumab - PART 1
Description
AEs, Deaths, other serious adverse events or discontinuations due to AE, Part I (Safety set)
Time Frame
During study parts I and II. The estimated study duration is not more than 216 weeks (with an average expected duration of 108 weeks).
Title
Number and Percentage of Patients With Adverse Events as a Measure of Long-term Safety and Tolerability of Canakinumab - PART 2
Description
AEs, Deaths, other serious adverse events or discontinuations due to AE, Part II (Safety set)
Time Frame
During study parts I and II, estimated study duration was not more than 216 weeks (with an average duration of 108 weeks).
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
Novartis Investigative Site
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Facility Name
Novartis Investigative Site
City
Vienna
ZIP/Postal Code
A-1090
Country
Austria
Facility Name
Novartis Investigative Site
City
Bruxelles
ZIP/Postal Code
1200
Country
Belgium
Facility Name
Novartis Investigative Site
City
Laeken
ZIP/Postal Code
1020
Country
Belgium
Facility Name
Novartis Investigative Site
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Novartis Investigative Site
City
Curitiba
State/Province
PR
ZIP/Postal Code
80250-030
Country
Brazil
Facility Name
Novartis Investigative Site
City
Rio de Janeiro
State/Province
RJ
ZIP/Postal Code
21941-912
Country
Brazil
Facility Name
Novartis Investigative Site
City
Sao Paulo
State/Province
SP
ZIP/Postal Code
05403-000
Country
Brazil
Facility Name
Novartis Investigative Site
City
Vancouver
State/Province
British Colombia
ZIP/Postal Code
V6H 3V4
Country
Canada
Facility Name
Novartis Investigative Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1X8
Country
Canada
Facility Name
Novartis Investigative Site
City
Bron Cedex
ZIP/Postal Code
69677
Country
France
Facility Name
Novartis Investigative Site
City
Le Kremlin Bicetre
ZIP/Postal Code
94275
Country
France
Facility Name
Novartis Investigative Site
City
Paris cedex 15
ZIP/Postal Code
75015
Country
France
Facility Name
Novartis Investigative Site
City
Sankt Augustin
State/Province
North Rhine-Westphalia
ZIP/Postal Code
53757
Country
Germany
Facility Name
Novartis Investigative Site
City
Berlin
ZIP/Postal Code
13125
Country
Germany
Facility Name
Novartis Investigative Site
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Novartis Investigative Site
City
Freiburg
ZIP/Postal Code
79106
Country
Germany
Facility Name
Novartis Investigative Site
City
Giessen
ZIP/Postal Code
35392
Country
Germany
Facility Name
Novartis Investigative Site
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
Novartis Investigative Site
City
Hamburg
ZIP/Postal Code
22081
Country
Germany
Facility Name
Novartis Investigative Site
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Novartis Investigative Site
City
Tübingen
ZIP/Postal Code
72076
Country
Germany
Facility Name
Novartis Investigative Site
City
Budapest
ZIP/Postal Code
1023
Country
Hungary
Facility Name
Novartis Investigative Site
City
Budapest
ZIP/Postal Code
1094
Country
Hungary
Facility Name
Novartis Investigative Site
City
Haifa
ZIP/Postal Code
3525408
Country
Israel
Facility Name
Novartis Investigative Site
City
Jerusalem
ZIP/Postal Code
91031
Country
Israel
Facility Name
Novartis Investigative Site
City
Kfar Saba
ZIP/Postal Code
4428164
Country
Israel
Facility Name
Novartis Investigative Site
City
Petach-Tikva
ZIP/Postal Code
49202
Country
Israel
Facility Name
Novartis Investigative Site
City
Ramat Gan
ZIP/Postal Code
5265601
Country
Israel
Facility Name
Novartis Investigative Site
City
Bologna
State/Province
BO
ZIP/Postal Code
40138
Country
Italy
Facility Name
Novartis Investigative Site
City
Genova
State/Province
GE
ZIP/Postal Code
16147
Country
Italy
Facility Name
Novartis Investigative Site
City
Milano
State/Province
MI
ZIP/Postal Code
20100
Country
Italy
Facility Name
Novartis Investigative Site
City
Roma
State/Province
RM
ZIP/Postal Code
00165
Country
Italy
Facility Name
Novartis Investigative Site
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
Novartis Investigative Site
City
Utrecht
ZIP/Postal Code
3584 EA
Country
Netherlands
Facility Name
Novartis Investigative Site
City
Warszawa
ZIP/Postal Code
02637
Country
Poland
Facility Name
Novartis Investigative Site
City
Moscow
ZIP/Postal Code
119991
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Saint-Petersburg
ZIP/Postal Code
194100
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Malaga
State/Province
Andalucia
ZIP/Postal Code
29011
Country
Spain
Facility Name
Novartis Investigative Site
City
Esplugues de Llobregat
State/Province
Barcelona
ZIP/Postal Code
08950
Country
Spain
Facility Name
Novartis Investigative Site
City
Valencia
State/Province
Comunidad Valenciana
ZIP/Postal Code
46026
Country
Spain
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28009
Country
Spain
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Novartis Investigative Site
City
Stockholm
ZIP/Postal Code
17176
Country
Sweden
Facility Name
Novartis Investigative Site
City
Istanbul
State/Province
TUR
ZIP/Postal Code
34098
Country
Turkey
Facility Name
Novartis Investigative Site
City
Ankara
ZIP/Postal Code
06100
Country
Turkey
Facility Name
Novartis Investigative Site
City
Istanbul
ZIP/Postal Code
34722
Country
Turkey
Facility Name
Novartis Investigative Site
City
Izmir
ZIP/Postal Code
35340
Country
Turkey
12. IPD Sharing Statement
Plan to Share IPD
Undecided
IPD Sharing Plan Description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Citations:
PubMed Identifier
32783351
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.
Results Reference
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ß-SPECIFIC 4 Patients: Study of Pediatric EffiCacy and Safety wIth FIrst-line Use of Canakinumab
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