ß-SPECIFIC 4 Patients: Study of Pediatric EffiCacy and Safety wIth FIrst-line Use of Canakinumab (ß-SPECIFIC 4)

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)

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.

Study Overview

• Status: Completed
• Conditions: Systemic Juvenile Idiopathic Arthritis (SJIA)
• Intervention / Treatment: Drug: ACZ885 150 mg (Canakinumab)

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.

• Study Type: Interventional
• Enrollment (Actual): 182
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, A-1090
    • Novartis Investigative Site
• Belgium
  • Bruxelles, Belgium, 1200
    • Novartis Investigative Site
  • Laeken, Belgium, 1020
    • Novartis Investigative Site
  • Leuven, Belgium, 3000
    • Novartis Investigative Site
• Brazil
  • PR
    • Curitiba, PR, Brazil, 80250-030
      • Novartis Investigative Site
  • RJ
    • Rio de Janeiro, RJ, Brazil, 21941-912
      • Novartis Investigative Site
  • SP
    • Sao Paulo, SP, Brazil, 05403-000
      • Novartis Investigative Site
• Canada
  • British Colombia
    • Vancouver, British Colombia, Canada, V6H 3V4
      • Novartis Investigative Site
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • Novartis Investigative Site
• France
  • Bron Cedex, France, 69677
    • Novartis Investigative Site
  • Le Kremlin Bicetre, France, 94275
    • Novartis Investigative Site
  • Paris cedex 15, France, 75015
    • Novartis Investigative Site
• Germany
  • Berlin, Germany, 13125
    • Novartis Investigative Site
  • Berlin, Germany, 13353
    • Novartis Investigative Site
  • Freiburg, Germany, 79106
    • Novartis Investigative Site
  • Giessen, Germany, 35392
    • Novartis Investigative Site
  • Hamburg, Germany, 20246
    • Novartis Investigative Site
  • Hamburg, Germany, 22081
    • Novartis Investigative Site
  • Heidelberg, Germany, 69120
    • Novartis Investigative Site
  • Tübingen, Germany, 72076
    • Novartis Investigative Site
  • North Rhine-Westphalia
    • Sankt Augustin, North Rhine-Westphalia, Germany, 53757
      • Novartis Investigative Site
• Hungary
  • Budapest, Hungary, 1023
    • Novartis Investigative Site
  • Budapest, Hungary, 1094
    • Novartis Investigative Site
• Israel
  • Haifa, Israel, 3525408
    • Novartis Investigative Site
  • Jerusalem, Israel, 91031
    • Novartis Investigative Site
  • Kfar Saba, Israel, 4428164
    • Novartis Investigative Site
  • Petach-Tikva, Israel, 49202
    • Novartis Investigative Site
  • Ramat Gan, Israel, 5265601
    • Novartis Investigative Site
• Italy
  • Napoli, Italy, 80131
    • Novartis Investigative Site
  • BO
    • Bologna, BO, Italy, 40138
      • Novartis Investigative Site
  • GE
    • Genova, GE, Italy, 16147
      • Novartis Investigative Site
  • MI
    • Milano, MI, Italy, 20100
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00165
      • Novartis Investigative Site
• Netherlands
  • Utrecht, Netherlands, 3584 EA
    • Novartis Investigative Site
• Poland
  • Warszawa, Poland, 02637
    • Novartis Investigative Site
• Russian Federation
  • Moscow, Russian Federation, 119991
    • Novartis Investigative Site
  • Saint-Petersburg, Russian Federation, 194100
    • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28034
    • Novartis Investigative Site
  • Madrid, Spain, 28046
    • Novartis Investigative Site
  • Madrid, Spain, 28009
    • Novartis Investigative Site
  • Andalucia
    • Malaga, Andalucia, Spain, 29011
      • Novartis Investigative Site
  • Barcelona
    • Esplugues de Llobregat, Barcelona, Spain, 08950
      • Novartis Investigative Site
  • Comunidad Valenciana
    • Valencia, Comunidad Valenciana, Spain, 46026
      • Novartis Investigative Site
• Sweden
  • Stockholm, Sweden, 17176
    • Novartis Investigative Site
• Turkey
  • Ankara, Turkey, 06100
    • Novartis Investigative Site
  • Istanbul, Turkey, 34722
    • Novartis Investigative Site
  • Izmir, Turkey, 35340
    • Novartis Investigative Site
  • TUR
    • Istanbul, TUR, Turkey, 34098
      • Novartis Investigative Site
• United States
  • California
    • Los Angeles, California, United States, 90027
      • Novartis Investigative Site
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 20 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Canakinumab Dose Reduction; 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.	Drug: ACZ885 150 mg (Canakinumab); Active canakinumab in individual 2 mL glass vials, each containing 150 mg canakinumab liquid in vial.; Other Names: ACZ885 150 mg
Experimental: Canakinumab Dose Interval Prolongation; 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.	Drug: ACZ885 150 mg (Canakinumab); Active canakinumab in individual 2 mL glass vials, each containing 150 mg canakinumab liquid in vial.; Other Names: ACZ885 150 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	baseline to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	During study parts I and II. The estimated study duration is not more than 216 weeks (with an average expected duration of 108 weeks).
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)	During study parts I and II, estimated study duration was not more than 216 weeks (with an average duration of 108 weeks).

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2014
• Primary Completion (Actual): October 14, 2016
• Study Completion (Actual): September 25, 2017

Study Registration Dates

• First Submitted: October 10, 2014
• First Submitted That Met QC Criteria: November 17, 2014
• First Posted (Estimate): November 20, 2014

Study Record Updates

• Last Update Posted (Actual): July 9, 2019
• Last Update Submitted That Met QC Criteria: June 17, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• 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)
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Juvenile; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: CACZ885G2306; 2013-004867-29 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

IPD 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No