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

NCT02296424 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: CACZ885G23062013-004867-29
• Study Type: interventional
• Target: 182
• Locations: 16 countries
• Sites: 50

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.

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)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Number and Percentage of Patients With Adverse Events as a Measure of Long-term Safety and Tolerability of Canakinumab - PART 1

  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

  During study parts I and II, estimated study duration was not more than 216 weeks (with an average duration of 108 weeks).

Study Arms (2)

Canakinumab Dose Reduction

EXPERIMENTAL

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)

Canakinumab Dose Interval Prolongation

EXPERIMENTAL

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)

Interventions

ACZ885 150 mg (Canakinumab) DRUG

Active canakinumab in individual 2 mL glass vials, each containing 150 mg canakinumab liquid in vial.

Also known as: ACZ885 150 mg

Canakinumab Dose Interval Prolongation; Canakinumab Dose Reduction

Eligibility Criteria

• Age: 2 Years - 20 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (50)

Novartis Investigative Site

Los Angeles, California, 90027, United States

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Novartis Investigative Site

Columbus, Ohio, 43205, United States

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Novartis Investigative Site

Vienna, A-1090, Austria

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Novartis Investigative Site

Brussels, 1200, Belgium

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Novartis Investigative Site

Laken, 1020, Belgium

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Novartis Investigative Site

Leuven, 3000, Belgium

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Novartis Investigative Site

Curitiba, Paraná, 80250-030, Brazil

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Novartis Investigative Site

Rio de Janeiro, Rio de Janeiro, 21941-912, Brazil

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Novartis Investigative Site

São Paulo, São Paulo, 05403-000, Brazil

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Novartis Investigative Site

Vancouver, British Colombia, V6H 3V4, Canada

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Novartis Investigative Site

Toronto, Ontario, M5G 1X8, Canada

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Novartis Investigative Site

Bron, 69677, France

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Novartis Investigative Site

Le Kremlin-Bicêtre, 94275, France

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Novartis Investigative Site

Paris, 75015, France

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Novartis Investigative Site

Sankt Augustin, North Rhine-Westphalia, 53757, Germany

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Novartis Investigative Site

Berlin, 13125, Germany

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Novartis Investigative Site

Berlin, 13353, Germany

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Novartis Investigative Site

Freiburg im Breisgau, 79106, Germany

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Novartis Investigative Site

Giessen, 35392, Germany

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Novartis Investigative Site

Hamburg, 20246, Germany

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Novartis Investigative Site

Hamburg, 22081, Germany

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Novartis Investigative Site

Heidelberg, 69120, Germany

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Novartis Investigative Site

Tübingen, 72076, Germany

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Novartis Investigative Site

Budapest, 1023, Hungary

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Novartis Investigative Site

Budapest, 1094, Hungary

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Novartis Investigative Site

Haifa, 3525408, Israel

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Novartis Investigative Site

Jerusalem, 91031, Israel

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Novartis Investigative Site

Kfar Saba, 4428164, Israel

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Novartis Investigative Site

Petah Tikva, 49202, Israel

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Novartis Investigative Site

Ramat Gan, 5265601, Israel

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Novartis Investigative Site

Bologna, BO, 40138, Italy

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Novartis Investigative Site

Genova, GE, 16147, Italy

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Novartis Investigative Site

Milan, MI, 20100, Italy

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Novartis Investigative Site

Roma, RM, 00165, Italy

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Novartis Investigative Site

Napoli, 80131, Italy

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Novartis Investigative Site

Utrecht, 3584 EA, Netherlands

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Novartis Investigative Site

Warsaw, 02637, Poland

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Novartis Investigative Site

Moscow, 119991, Russia

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Novartis Investigative Site

Saint Petersburg, 194100, Russia

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Novartis Investigative Site

Málaga, Andalusia, 29011, Spain

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Novartis Investigative Site

Esplugues de Llobregat, Barcelona, 08950, Spain

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Novartis Investigative Site

Valencia, Valencia, 46026, Spain

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Novartis Investigative Site

Madrid, 28009, Spain

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Novartis Investigative Site

Madrid, 28034, Spain

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Novartis Investigative Site

Madrid, 28046, Spain

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Novartis Investigative Site

Stockholm, 17176, Sweden

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Novartis Investigative Site

Istanbul, TUR, 34098, Turkey (Türkiye)

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Novartis Investigative Site

Ankara, 06100, Turkey (Türkiye)

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Novartis Investigative Site

Istanbul, 34722, Turkey (Türkiye)

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Novartis Investigative Site

Izmir, 35340, Turkey (Türkiye)

Location

Related Publications (1)

• 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.

  PMID: 32783351 DERIVED

MeSH Terms

Conditions

Arthritis, Juvenile; Bronchiolitis Obliterans Syndrome; Arthralgia; Rheumatoid Arthritis, Systemic Juvenile

Interventions

canakinumab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Clinical Disclosure Office
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

+1 (862) 778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: No blinding was required in this open-label study
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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)

Study Record Dates

• First Submitted: October 10, 2014
• First Posted: November 20, 2014
• Study Start: November 17, 2014
• Primary Completion: October 14, 2016
• Study Completion: September 25, 2017
• Last Updated: July 9, 2019
• Results First Posted: July 9, 2019

Record last verified: 2019-06

Locations

NL (1); IL (5); IT (5); TU (4); BE (3); RU (2); DE (9); US (2); CA (2); BR (3); ES (6); FR (3); PL (1); HU (2); AU (1); SE (1)