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

NCT ID: NCT01676948

Last Updated: 2015-10-15

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-01-31
• Study Completion Date: 2015-01-31

Brief Summary

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.

Conditions

Systemic Juvenile Idiopathic Arthritis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Canakinumab - Cohort 1, 2mg

2 mg/kg q4wk (followed by taper to 1 mg/kg q4wk and drug discontinuation if appropriate)

Group Type: EXPERIMENTAL

Canakinumab

Intervention Type: DRUG

Canakinumab

Intervention Type: DRUG

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

Canakinumab

Intervention Type: DRUG

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

Canakinumab - Cohort 1, 4mg

4 mg/kg q8wk (followed by taper to 4 mg/kg q12wk and drug discontinuation if appropriate)

Group Type: EXPERIMENTAL

Canakinumab

Intervention Type: DRUG

Canakinumab

Intervention Type: DRUG

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

Canakinumab - Cohort 2, 2mg

2 mg/kg q4wk (followed by taper to 1 mg/kg q4wk and drug discontinuation if appropriate)

Group Type: EXPERIMENTAL

Canakinumab

Intervention Type: DRUG

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

Canakinumab

Intervention Type: DRUG

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

Canakinumab - Cohort 2, 4mg

4 mg/kg q8wk (followed by taper to 4 mg/kg q12wk and drug discontinuation if appropriate)

Group Type: EXPERIMENTAL

Canakinumab

Intervention Type: DRUG

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

Cohort 2 - canakinumab dose reduction

Group Type: EXPERIMENTAL

ACZ885

Intervention Type: DRUG

Cohort 1 - canakinumab dose reduction

Group Type: EXPERIMENTAL

ACZ885

Intervention Type: DRUG

Interventions

ACZ885

Intervention Type: DRUG

Canakinumab

Intervention Type: DRUG

Canakinumab

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

Intervention Type: DRUG

Canakinumab

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

Intervention Type: DRUG

Eligibility Criteria

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

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:

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

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

PRINTO / PRCSG

UNKNOWN

Sponsor Role: collaborator

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Other Identifiers

2012-003054-92

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CACZ885G2402

Identifier Type: -

Identifier Source: org_study_id