<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01676948</url>
  </required_header>
  <id_info>
    <org_study_id>CACZ885G2402</org_study_id>
    <secondary_id>2012-003054-92</secondary_id>
    <nct_id>NCT01676948</nct_id>
  </id_info>
  <brief_title>An Open-label, Multi-arm, Non-comparative Safety and Tolerability Study of Canakinumab (ACZ885) in Patients With Active Systemic Juvenile Idiopathic Arthritis (SJIA)</brief_title>
  <acronym>β-SPECIFIC 4Pa</acronym>
  <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)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>PRINTO / PRCSG</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Novartis</source>
  <brief_summary>
    <textblock>
      This two-part open-label, multi-arm, non-comparative study will collect long-term safety,&#xD;
      efficacy and tolerability data from patients who were responsive to canakinumab from study&#xD;
      CACZ885G2301E1 (Cohort 1), and from patients who are treatment naïve to canakinumab (Cohort&#xD;
      2). In addition, the effect of inactivated vaccines in an SJIA patient population will be&#xD;
      assessed for the development of adequate (protective) antibody levels following immunization&#xD;
      according to respective local vaccination guidelines.&#xD;
&#xD;
      Study Part I:&#xD;
&#xD;
      All patients will be treated with canakinumab 4 mg/kg every 4 weeks (or 2 mg/kg every 4 weeks&#xD;
      for Cohort 1 patients who are receiving that dose in CACZ885G2301E1) until study end unless&#xD;
      discontinuation occurs, or until they qualify for Part II of the study.&#xD;
&#xD;
      Study Part II:&#xD;
&#xD;
      Patients who are eligible will be randomized to receive canakinumab at a reduced dose or&#xD;
      prolonged dose interval (see requirements for dose reduction/dose interval prolongation&#xD;
      below).&#xD;
&#xD;
      Patients in Cohort 1 receiving 2 mg/kg q4wk in CACZ885G2301E1 will not be randomized but will&#xD;
      be part of the treatment arm canakinumab dose reduction if they are eligible.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <start_date>January 2013</start_date>
  <completion_date type="Actual">January 2015</completion_date>
  <primary_completion_date type="Actual">January 2015</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Long-term safety and tolerability of canakinumab and the retention rate of canakinumab-treated patients</measure>
    <time_frame>Days 1 to 533</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The percentage of patients who meet the adapted pediatric ACR, its individual components, and the Juvenile Arthritis Disease Activity Score [JADAS] over time</measure>
    <time_frame>Days 1 to 533</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The level of systemic corticosteroid tapering achieved in Part I</measure>
    <time_frame>Day 1 to start of Part II</time_frame>
    <description>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 &gt;0-&lt;0.2 mg/kg and those who reach corticosteroid free regimen.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The level of canakinumab tapering achieved after randomization to the dose reduction arm or dose interval prolongation treatment arm in Part II</measure>
    <time_frame>from start of Part II to Day 533</time_frame>
    <description>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.&#xD;
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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The time to treatment failure in Part II</measure>
    <time_frame>from start of Part II to Day 533</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Systemic Juvenile Idiopathic Arthritis</condition>
  <arm_group>
    <arm_group_label>Canakinumab - Cohort 1, 2mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>2 mg/kg q4wk (followed by taper to 1 mg/kg q4wk and drug discontinuation if appropriate)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Canakinumab - Cohort 1, 4mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>4 mg/kg q8wk (followed by taper to 4 mg/kg q12wk and drug discontinuation if appropriate)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Canakinumab - Cohort 2, 2mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>2 mg/kg q4wk (followed by taper to 1 mg/kg q4wk and drug discontinuation if appropriate)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Canakinumab - Cohort 2, 4mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>4 mg/kg q8wk (followed by taper to 4 mg/kg q12wk and drug discontinuation if appropriate)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2 - canakinumab dose reduction</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 1 - canakinumab dose reduction</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ACZ885</intervention_name>
    <arm_group_label>Cohort 1 - canakinumab dose reduction</arm_group_label>
    <arm_group_label>Cohort 2 - canakinumab dose reduction</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Canakinumab</intervention_name>
    <arm_group_label>Canakinumab - Cohort 1, 2mg</arm_group_label>
    <arm_group_label>Canakinumab - Cohort 1, 4mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Canakinumab</intervention_name>
    <description>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.&#xD;
Canakinumab-naïve patients</description>
    <arm_group_label>Canakinumab - Cohort 1, 2mg</arm_group_label>
    <arm_group_label>Canakinumab - Cohort 2, 2mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Canakinumab</intervention_name>
    <description>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</description>
    <arm_group_label>Canakinumab - Cohort 1, 2mg</arm_group_label>
    <arm_group_label>Canakinumab - Cohort 1, 4mg</arm_group_label>
    <arm_group_label>Canakinumab - Cohort 2, 2mg</arm_group_label>
    <arm_group_label>Canakinumab - Cohort 2, 4mg</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key inclusion criteria:&#xD;
&#xD;
        Cohort 1:&#xD;
&#xD;
        1. All patients currently enrolled in study CACZ885G2301E1, including patients who&#xD;
        discontinued canakinumab therapy for inactive disease in CACZ885G2301E1 as per physician&#xD;
        discretion and who are now currently in a flare and require canakinumab therapy again&#xD;
&#xD;
        Cohort 2:&#xD;
&#xD;
          1. Male and female patients aged ≥ 2 to &lt; 20 years at the time of the screening visit&#xD;
&#xD;
          2. Confirmed diagnosis of SJIA as per ILAR definition that must have occurred at least 2&#xD;
             months prior to enrollment with an onset of disease &lt; 16 years of age:&#xD;
&#xD;
             • Arthritis in one or more joints, with or preceded by fever of at least 2 weeks&#xD;
             duration that is documented to be daily/quotidian for at least 3 days and accompanied&#xD;
             by one or more of the following:&#xD;
&#xD;
               -  Evanescent non-fixed erythematous rash,&#xD;
&#xD;
               -  Generalized lymph node enlargement,&#xD;
&#xD;
               -  Hepatomegaly and/ or splenomegaly,&#xD;
&#xD;
               -  Serositis&#xD;
&#xD;
          3. Active systemic disease at the time of baseline visit defined as having 2 or more of&#xD;
             the following:&#xD;
&#xD;
               -  Documented spiking, intermittent fever (body temperature &gt; 38°C) for at least 1&#xD;
                  day during the screening period and within 1 week before first canakinumab dose,&#xD;
&#xD;
               -  At least 2 joints with active arthritis (using ACR definition of active joint),&#xD;
&#xD;
               -  C-reactive protein (CRP) &gt; 30 mg/L (normal range &lt; 10 mg/L),&#xD;
&#xD;
               -  Rash,&#xD;
&#xD;
               -  Serositis,&#xD;
&#xD;
               -  Lymphadenopathy,&#xD;
&#xD;
               -  Hepatosplenomegaly&#xD;
&#xD;
          4. Patient's willingness to discontinue anakinra, rilonacept, tocilizumab or other&#xD;
             experimental drug under close monitoring&#xD;
&#xD;
          5. Patients who are scheduled to receive an immunization, according to their local&#xD;
             vaccination guidelines, with an inactivated vaccine and willing to participate in the&#xD;
             assessment schedule for vaccinated patients&#xD;
&#xD;
        Key exclusion criteria:&#xD;
&#xD;
        Cohort 1 and Cohort 2:&#xD;
&#xD;
          1. Active or recurrent bacterial, fungal or viral infection at the time of enrollment&#xD;
&#xD;
          2. Underlying metabolic, renal, hepatic, infectious or gastrointestinal conditions which&#xD;
             in the opinion of the investigator immunocompromises the patient and/ or places the&#xD;
             patient at unacceptable risk for participation in an immunomodulatory therapy.&#xD;
&#xD;
          3. History of malignancy of any organ system (other than localized basal cell carcinoma&#xD;
             of the skin), treated or untreated, within the past 5 years, regardless of whether&#xD;
             there is evidence of local recurrence or metastases.&#xD;
&#xD;
          4. Live vaccinations within 3 months prior to the start of the study.&#xD;
&#xD;
        Cohort 2:&#xD;
&#xD;
        The following additional key exclusion criteria apply for Cohort 2.&#xD;
&#xD;
          1. Presence of moderate to severe impaired renal function&#xD;
&#xD;
          2. Clinical evidence of liver disease or liver injury as indicated by abnormal liver&#xD;
             function tests at screening&#xD;
&#xD;
          3. History/evidence of macrophage activation syndrome within the previous 6 months&#xD;
&#xD;
        Other protocol-defined inclusion/exclusion criteria may apply.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Years</minimum_age>
    <maximum_age>20 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Novartis Pharmaceuticals</last_name>
    <role>Study Director</role>
    <affiliation>Novartis Pharmaceuticals</affiliation>
  </overall_official>
  <removed_countries>
    <country>Argentina</country>
    <country>Austria</country>
    <country>Belgium</country>
    <country>Brazil</country>
    <country>Canada</country>
    <country>France</country>
    <country>Germany</country>
    <country>Greece</country>
    <country>Hungary</country>
    <country>Israel</country>
    <country>Italy</country>
    <country>Netherlands</country>
    <country>Poland</country>
    <country>Russian Federation</country>
    <country>Spain</country>
    <country>Sweden</country>
    <country>Switzerland</country>
    <country>Turkey</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </removed_countries>
  <verification_date>October 2015</verification_date>
  <study_first_submitted>August 29, 2012</study_first_submitted>
  <study_first_submitted_qc>August 29, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 31, 2012</study_first_posted>
  <last_update_submitted>October 13, 2015</last_update_submitted>
  <last_update_submitted_qc>October 13, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 15, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>SJIA</keyword>
  <keyword>Systemic Juvenile Idiopathic Arthritis</keyword>
  <keyword>children</keyword>
  <keyword>systemic autoinflammatory disease, ACZ885, canakinumab</keyword>
  <keyword>human monoclonal anti-interleukin-1β (IL-1 β) antibody</keyword>
  <keyword>hildhood immunizations vaccinations</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Arthritis</mesh_term>
    <mesh_term>Arthritis, Juvenile</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Antibodies, Monoclonal</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01676948
org study id: CACZ885G2402
secondary id: 2012-003054-92
nct id: NCT01676948
lead sponsor: 
collaborator: 
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.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Long-term safety and tolerability of canakinumab and the retention rate of canakinumab-treated patients
time frame: Days 1 to 533
description: 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.
measure: 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
description: 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.
measure: The level of systemic corticosteroid tapering achieved in Part I
time frame: Day 1 to start of Part II
description: 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.
measure: 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
description: 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.
measure: The time to treatment failure in Part II
time frame: from start of Part II to Day 533
description: 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.
arm group label: Canakinumab - Cohort 1, 2mg
arm group type: Experimental
description: 2 mg/kg q4wk (followed by taper to 1 mg/kg q4wk and drug discontinuation if appropriate)
arm group label: Canakinumab - Cohort 1, 4mg
arm group type: Experimental
description: 4 mg/kg q8wk (followed by taper to 4 mg/kg q12wk and drug discontinuation if appropriate)
arm group label: Canakinumab - Cohort 2, 2mg
arm group type: Experimental
description: 2 mg/kg q4wk (followed by taper to 1 mg/kg q4wk and drug discontinuation if appropriate)
arm group label: Canakinumab - Cohort 2, 4mg
arm group type: Experimental
description: 4 mg/kg q8wk (followed by taper to 4 mg/kg q12wk and drug discontinuation if appropriate)
arm group label: Cohort 2 - canakinumab dose reduction
arm group type: Experimental
arm group label: Cohort 1 - canakinumab dose reduction
arm group type: Experimental
intervention type: Drug
intervention name: ACZ885
arm group label: Cohort 1 - canakinumab dose reduction
arm group label: Cohort 2 - canakinumab dose reduction
intervention type: Drug
intervention name: Canakinumab
arm group label: Canakinumab - Cohort 1, 2mg
arm group label: Canakinumab - Cohort 1, 4mg
intervention type: Drug
intervention name: Canakinumab
description: 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
arm group label: Canakinumab - Cohort 1, 2mg
arm group label: Canakinumab - Cohort 2, 2mg
intervention type: Drug
intervention name: Canakinumab
description: 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
arm group label: Canakinumab - Cohort 1, 2mg
arm group label: Canakinumab - Cohort 1, 4mg
arm group label: Canakinumab - Cohort 2, 2mg
arm group label: Canakinumab - Cohort 2, 4mg
criteria: 
gender: All
minimum age: 2 Years
maximum age: 20 Years
healthy volunteers: No
last name: Novartis Pharmaceuticals
role: Study Director
affiliation: Novartis Pharmaceuticals
country: Argentina
country: Austria
country: Belgium
country: Brazil
country: Canada
country: France
country: Germany
country: Greece
country: Hungary
country: Israel
country: Italy
country: Netherlands
country: Poland
country: Russian Federation
country: Spain
country: Sweden
country: Switzerland
country: Turkey
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Arthritis
mesh term: Arthritis, Juvenile
mesh term: Antibodies, Monoclonal