Trial record 16 of 132 for:    "juvenile idiopathic arthritis" OR "Arthritis, Juvenile Rheumatoid"

An Open-label, Multi-arm, Non-comparative Safety and Tolerability Study of Canakinumab (ACZ885) in Patients With Active Systemic Juvenile Idiopathic Arthritis (SJIA) (β-SPECIFIC 4Pa)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified March 2014 by Novartis
Sponsor:
Collaborator:
PRINTO/PRCSG
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01676948
First received: August 29, 2012
Last updated: March 6, 2014
Last verified: March 2014
  Purpose

This two-part open-label, multi-arm, non-comparative study will collect long-term safety, efficacy and tolerability data from patients who were responsive to canakinumab from study CACZ885G2301E1 (Cohort 1), and from patients who are treatment naïve to canakinumab (Cohort 2). In addition, the effect of inactivated vaccines in an SJIA patient population will be assessed for the development of adequate (protective) antibody levels following immunization according to respective local vaccination guidelines.

Study Part I:

All patients will be treated with canakinumab 4 mg/kg every 4 weeks (or 2 mg/kg every 4 weeks for Cohort 1 patients who are receiving that dose in CACZ885G2301E1) until study end unless discontinuation occurs, or until they qualify for Part II of the study.

Study Part II:

Patients who are eligible will be randomized to receive canakinumab at a reduced dose or prolonged dose interval (see requirements for dose reduction/dose interval prolongation below).

Patients in Cohort 1 receiving 2 mg/kg q4wk in CACZ885G2301E1 will not be randomized but will be part of the treatment arm canakinumab dose reduction if they are eligible.


Condition Intervention Phase
Systemic Juvenile Idiopathic Arthritis
Drug: Canakinumab - Cohort 1
Drug: Canakinumab - Cohort 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Multi-arm, Non-comparative Safety and Tolerability Study of Canakinumab (ACZ885) in Patients With Active Systemic Juvenile Idiopathic Arthritis (SJIA)

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Long-term safety and tolerability of canakinumab and the retention rate of canakinumab-treated patients [ Time Frame: Days 1 to 533 ] [ Designated as safety issue: Yes ]
    Outcome Measure Description: The long-term safety and tolerability of canakinumab and the retention rate of canakinumab-treated patients will be evaluated by monitoring of serious adverse events and adverse events leading to discontinuation of study drug.


Secondary Outcome Measures:
  • The percentage of patients who meet the adapted pediatric ACR, its individual components, and the Juvenile Arthritis Disease Activity Score [JADAS] over time [ Time Frame: Days 1 to 533 ] [ Designated as safety issue: No ]
    Outcome Measure Description: Patients will be classified into the adapted pediatric ACR categories to characterize their magnitude of efficacy response. JADAS will be derived from physician global assessment, parent/patient global assessment, active joint count and CRP.

  • The level of systemic corticosteroid tapering achieved in Part I [ Time Frame: Day 1 to start of Part II ] [ Designated as safety issue: No ]
    Patients will be classified into the following 3 categories: ≥ 0.2 mg/kg at end of Part I, those who reach a corticosteroid dose between >0-<0.2 mg/kg and those who reach corticosteroid free regimen.

  • The level of canakinumab tapering achieved after randomization to the dose reduction arm or dose interval prolongation treatment arm in Part II [ Time Frame: from start of Part II to Day 533 ] [ Designated as safety issue: No ]

    In the canakinumab dose reduction arm, patients will be classified into the following 3 categories: Number of patients who are able to reach 1mg/kg q4wk at the end of Part II, canakinumab free regimen by the end of Part II and those who come back to 2mg/kg q4wk at the end of Part II.

    In the canakinumab dose interval arm, patients will be classified into the following 3 categories: Number of patients who are able to reach 4mg/kg q12wk at the end of Part II, canakinumab-free regimen by the end of Part II and those who come back to 4mg/kg q8wk at the end of Part II.


  • The time to treatment failure in Part II [ Time Frame: from start of Part II to Day 533 ] [ Designated as safety issue: No ]
    Time to treatment failure (TTF) is defined as time from randomization to the date when the patient's worsened SJIA disease activity requires increasing the doze or shortening the treatment interval of canakinumab or the date the patient is withdrawn from the study due to a safety concern.


Estimated Enrollment: 220
Study Start Date: November 2012
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Canakinumab - Cohort 1, 2mg
2 mg/kg q4wk (followed by taper to 1 mg/kg q4wk and drug discontinuation if appropriate)
Drug: Canakinumab - Cohort 1

Patients rolling over into this study from CACZ885G2301E1 (Cohort 1) will continue on their established canakinumab dose of either 4 mg/kg SC given every 4 weeks or 2mg/kg SC given every 4 weeks, until eligible for dose reduction.

Canakinumab-naïve patients

Other Name: Canakinumab
Experimental: Canakinumab - Cohort 1, 4mg
4 mg/kg q8wk (followed by taper to 4 mg/kg q12wk and drug discontinuation if appropriate)
Drug: Canakinumab - Cohort 1

Patients rolling over into this study from CACZ885G2301E1 (Cohort 1) will continue on their established canakinumab dose of either 4 mg/kg SC given every 4 weeks or 2mg/kg SC given every 4 weeks, until eligible for dose reduction.

Canakinumab-naïve patients

Other Name: Canakinumab
Experimental: Canakinumab - Cohort 2, 2mg
2 mg/kg q4wk (followed by taper to 1 mg/kg q4wk and drug discontinuation if appropriate)
Drug: Canakinumab - Cohort 2
Patients rolling over into this study from CACZ885G2301E1(Cohort 2) will receive a standard canakinumab dose of 4mg/kg SC given every 4 weeks, until eligible for dose reduction
Other Name: canakinumab
Experimental: Canakinumab - Cohort 2, 4mg
4 mg/kg q8wk (followed by taper to 4 mg/kg q12wk and drug discontinuation if appropriate)
Drug: Canakinumab - Cohort 2
Patients rolling over into this study from CACZ885G2301E1(Cohort 2) will receive a standard canakinumab dose of 4mg/kg SC given every 4 weeks, until eligible for dose reduction
Other Name: canakinumab
Experimental: Cohort 2 - canakinumab dose reduction Drug: Canakinumab - Cohort 2
Patients rolling over into this study from CACZ885G2301E1(Cohort 2) will receive a standard canakinumab dose of 4mg/kg SC given every 4 weeks, until eligible for dose reduction
Other Name: canakinumab
Experimental: Cohort 1 - canakinumab dose reduction Drug: Canakinumab - Cohort 1

Patients rolling over into this study from CACZ885G2301E1 (Cohort 1) will continue on their established canakinumab dose of either 4 mg/kg SC given every 4 weeks or 2mg/kg SC given every 4 weeks, until eligible for dose reduction.

Canakinumab-naïve patients

Other Name: Canakinumab

  Eligibility

Ages Eligible for Study:   2 Years to 20 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Key inclusion criteria:

Cohort 1:

1. All patients currently enrolled in study CACZ885G2301E1, including patients who discontinued canakinumab therapy for inactive disease in CACZ885G2301E1 as per physician discretion and who are now currently in a flare and require canakinumab therapy again

Cohort 2:

  1. Male and female patients aged ≥ 2 to < 20 years at the time of the screening visit
  2. Confirmed diagnosis of SJIA as per ILAR definition that must have occurred at least 2 months prior to enrollment with an 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 non-fixed erythematous rash,
    • Generalized lymph node enlargement,
    • Hepatomegaly and/ or splenomegaly,
    • Serositis
  3. Active systemic disease at the time of baseline visit defined as having 2 or more of the following:

    • Documented spiking, intermittent fever (body temperature > 38°C) for at least 1 day during the screening period and within 1 week before first canakinumab dose,
    • At least 2 joints with active arthritis (using ACR definition of active joint),
    • C-reactive protein (CRP) > 30 mg/L (normal range < 10 mg/L),
    • Rash,
    • Serositis,
    • Lymphadenopathy,
    • Hepatosplenomegaly
  4. Patient's willingness to discontinue anakinra, rilonacept, tocilizumab or other experimental drug under close monitoring
  5. Patients who are scheduled to receive an immunization, according to their local vaccination guidelines, with an inactivated vaccine and willing to participate in the assessment schedule for vaccinated patients

Key exclusion criteria:

Cohort 1 and Cohort 2:

  1. Active or recurrent bacterial, fungal or viral infection at the time of enrollment
  2. 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 in an immunomodulatory therapy.
  3. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
  4. Live vaccinations within 3 months prior to the start of the study.

Cohort 2:

The following additional key exclusion criteria apply for Cohort 2.

  1. Presence of moderate to severe impaired renal function
  2. Clinical evidence of liver disease or liver injury as indicated by abnormal liver function tests at screening
  3. History/evidence of macrophage activation syndrome within the previous 6 months

Other protocol-defined inclusion/exclusion criteria may apply.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01676948

Contacts
Contact: Novartis Pharmaceuticals +1 862-778-8300

  Show 63 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
PRINTO/PRCSG
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01676948     History of Changes
Other Study ID Numbers: CACZ885G2402, 2012-003054-92
Study First Received: August 29, 2012
Last Updated: March 6, 2014
Health Authority: Argentina: Ministry of Health
Austria: Agency for Health and Food Safety
Belgium: Federal Agency for Medicinal and Health Products
Brazil: Ministry of Health
Canada: Health Canada
Czech Republic: State Institute for Drug Control
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Paul-Ehrlich-Institut (PEI)
Greece: National Organization for Medicines
Hungary: National Institute of Pharmacy
Israel: Ministry of Health
Italy: Ministry of Health
Netherlands: Central Committee on Research Involving Human Subjects (CCMO)
Peru: Ministry of Health
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Russia: Federal Service on Surveillance in Healthcare and Social Development
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Switzerland: Swissmedic
Turkey: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Keywords provided by Novartis:
SJIA
Systemic Juvenile Idiopathic Arthritis
children
systemic autoinflammatory disease, ACZ885, canakinumab
human monoclonal anti-interleukin-1β (IL-1 β) antibody
childhood immunizations vaccinations

Additional relevant MeSH terms:
Arthritis
Arthritis, Juvenile
Autoimmune Diseases
Connective Tissue Diseases
Immune System Diseases
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Antibodies, Monoclonal
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 23, 2014