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A Study to Evaluate Efficacy and Safety of Anakinra in the Treatment of Still's Disease (SJIA and AOSD) (anaSTILLs)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03265132
Recruitment Status : Terminated (Meeting enrolment target (81 pat) will not be feasible within reasonable time.)
First Posted : August 29, 2017
Results First Posted : February 28, 2020
Last Update Posted : April 28, 2020
Sponsor:
Information provided by (Responsible Party):
Swedish Orphan Biovitrum

Tracking Information
First Submitted Date  ICMJE August 25, 2017
First Posted Date  ICMJE August 29, 2017
Results First Submitted Date  ICMJE February 12, 2020
Results First Posted Date  ICMJE February 28, 2020
Last Update Posted Date April 28, 2020
Actual Study Start Date  ICMJE September 26, 2017
Actual Primary Completion Date February 13, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 10, 2019)
Proportion of ACR30 Responders With Absence of Fever Attributable to the Disease During the 7 Days Preceding Week 2. [ Time Frame: Week 2 ]
ACR30 response is defined as an improvement of ≥ 30% from baseline in at least 3 of any 6 variables listed below. Also no more than 1 of the 6 variables may worsen by >30% from baseline. (ACR: American College of Rheumatology)
  1. Physician global assessment of disease activity - Assessed on a Visual Analogue Scale (VAS) from no disease activity (0 mm) to very severe disease activity (100 mm).
  2. Patient/parent global assessment of overall well-being - Assessed on a VAS from very well (0 mm) to very poor (100 mm).
  3. Number of joints with active arthritis.
  4. Number of joints with limitation of motion.
  5. Assessment of physical function - Patient Reported Outcome instruments : Childhood Health Assessment Questionnaire (CHAQ) /Stanford Health Assessment Questionnaire (SHAQ).
  6. C-Reactive Protein (CRP) (mg/L).
Original Primary Outcome Measures  ICMJE
 (submitted: August 25, 2017)
Proportion of ACR30 Responders With Absence of Fever Attributable to the Disease During the 7 Days Preceding Week 2. [ Time Frame: Week 2 ]
ACR30 response is defined as an improvement of ≥ 30% from baseline in at least 3 of any 6 variables listed below. Also no more than 1 of the 6 variables may worsen by >30% from baseline. (ACR: American College of Rheumatology)
  1. Physician global assessment of disease activity - Assessed on a Visual Analogue Scale (VAS) from no disease activity (0 mm) to very severe disease activity (100 mm).
  2. Patient/parent global assessment of overall well-being - Assessed on a VAS from very well (0 mm) to very poor (100 mm).
  3. Number of joints with active arthritis.
  4. Number of joints with limitation of movement.
  5. Assessment of physical function - Patient Reported Outcome instruments : Childhood Health Assessment Questionnaire (CHAQ) /Stanford Health Assessment Questionnaire (SHAQ).
  6. C-Reactive Protein (CRP) (mg/L).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 17, 2020)
  • Proportion of ACR30 Responders With Absence of Fever During 24 Hours Preceding Week 1. [ Time Frame: Week 1 ]
    ACR30 response is defined as an improvement of ≥ 30% from baseline in at least 3 of any 6 variables listed in the description of the primary outcome measure. Also no more than 1 of the 6 variables may worsen by >30% from baseline.
  • Proportion of ACR50 Responders With Absence of Fever During 24 Hours Preceding Week 1. [ Time Frame: Week 1 ]
    ACR50 response is defined as an improvement of ≥ 50% from baseline in at least 3 of any 6 variables listed in the description of the primary outcome measure. Also no more than 1 of the 6 variables may worsen by >30% from baseline.
  • Proportion of ACR70 Responders With Absence of Fever During 24 Hours Preceding Week 1. [ Time Frame: Week 1 ]
    ACR70 response is defined as an improvement of ≥ 70% from baseline in at least 3 of any 6 variables listed in the description of the primary outcome measure. Also no more than 1 of the 6 variables may worsen by >30% from baseline.
  • Proportion of ACR90 Responders With Absence of Fever During 24 Hours Preceding Week 1. [ Time Frame: Week 1 ]
    ACR90 response is defined as an improvement of ≥ 90% from baseline in at least 3 of any 6 variables listed in the description of the primary outcome measure. Also no more than 1 of the 6 variables may worsen by >30% from baseline.
  • Proportion of ACR50 Responders With Absence of Fever During 7 Days Preceding Week 2. [ Time Frame: Week 2 ]
    ACR50 response is defined as an improvement of ≥ 50% from baseline in at least 3 of any 6 variables listed in the description of the primary outcome measure. Also no more than 1 of the 6 variables may worsen by >30% from baseline.
  • Proportion of ACR70 Responders With Absence of Fever During 7 Days Preceding Week 2. [ Time Frame: Week 2 ]
    ACR70 response is defined as an improvement of ≥ 70% from baseline in at least 3 of any 6 variables listed in the description of the primary outcome. Also no more than 1 of the 6 variables may worsen by >30% from baseline.
  • Proportion of ACR90 Responders With Absence of Fever During 7 Days Preceding Week 2. [ Time Frame: Week 2 ]
    ACR90 response is defined as an improvement of ≥ 90% from baseline in at least 3 of any 6 variables listed in the description of the primary outcome . Also no more than 1 of the 6 variables may worsen by >30% from baseline.
  • Proportion of Responders in Physician Global Assessment of Disease Activity. [ Time Frame: Week 2 ]
    Assessed on a VAS from no disease activity (0 mm) to very severe disease activity (100 mm). Response is defined as an improvement of ≥ 30%, 50%, 70% and 90% from baseline. Only improvement of ≥90% at Week 2 reported here.
  • Proportion of Responders in Patient/Parent Global Assessment of Overall Well-being. [ Time Frame: Week 2 ]
    Assessed on a VAS from very well (0 mm) to very poor. (100 mm). Response is defined as an improvement of ≥ 30%, 50%, 70% and 90% from baseline.Only improvement of ≥90% at Week 2 reported here.
  • Proportion of Responders in Number of Joints With Active Arthritis. [ Time Frame: Week 2 ]
    Response is defined as an improvement of ≥ 30%, 50%, 70% and 90% from baseline.Only improvement of ≥90% at Week 2 reported here.
  • Proportion of Responders in Number of Joints With Limitation of Motion. [ Time Frame: Week 2 ]
    Response is defined as an improvement of ≥ 30%, 50%, 70% and 90% from baseline.Only improvement of ≥90% at Week 2 reported here.
  • Proportion of Responders in Assessment of Physical Function (CHAQ/SHAQ). [ Time Frame: Week 2 ]
    Childhood Health Assessment Questionnaire (CHAQ) and Stanford Health Assessment Questionnaire (SHAQ) assess physical and functional status (see Clinical protocol section 6.5.4.1.5). Response is defined as an improvement of ≥ 30%, 50%, 70% and 90% from baseline. Only improvement of ≥90% at Week 2 reported here.
  • Proportion of Responders in CRP (mg/L). [ Time Frame: Week 2 ]
    Response is defined as an improvement of ≥ 30%, 50%, 70% and 90% from baseline. Only improvement of ≥90% at Week 2 reported here.
  • Proportion of Patients With Absence of Fever During the 7 Days Preceding Week 2. [ Time Frame: Week 2 ]
    Proportion of patients with absence of fever during the 7 days preceding Week 2.
  • Proportion of Patients With Absence of Fever During the 24 Hours Preceding Week 1. [ Time Frame: Week 1 ]
    Absence of fever during the 24 hours preceding week 1.
  • Change From Baseline in Physician Global Assessment of Disease Activity at Week 1. [ Time Frame: Day 1 and Week 1 ]
    Change from baseline in Physician global assessment of disease activity measured on a VAS 0 (very well)-100 (very poor) at Week 1.
  • Change From Baseline in Patient/Parent Global Assessment of Overall Well-being at Week 1. [ Time Frame: Day 1 and Week 1 ]
    Change from baseline in patient/parent global assessment of overall well-being measured on a VAS 0 (very well)-100 (very poor) at Week 1.
  • Change From Baseline in CRP. [ Time Frame: Day 1 and Week 1 ]
    Change from baseline in C-Reactive Protein (CRP). CRP is measured in mg/L.
  • Proportion of Patients With Sustained ACR30, ACR50, ACR70 and ACR90 Response. [ Time Frame: Week 12 ]
    Proportion of patients that still meet the corresponding week 2 response with absence of fever in the preceding 7 days. Only the strictest criteria, ACR90, is reported here.
  • Proportion of Patients With Sustained ACR30, ACR50, ACR70 and ACR90 Response in Relation to Glucocorticoid Tapering. [ Time Frame: Week 2, Week 4, Week 8 and Week 12 ]
    Please note no patients were treated with any systemic glucocorticoids at randomization. Hence no results available.
  • Proportion of Patients With Absence of Rash. [ Time Frame: Week 2 ]
    Absence of rash is evaluated 24 hours preceding Week 1 and 7 days preceding Week 2, Week 4, Week 8 and Week 12. Only data at Week 2 reported here.
  • Change From Baseline in CRP. [ Time Frame: Week 2 ]
    Change from baseline in CRP. Results at Week 2 reported here.
  • Change From Baseline in Hemoglobin (Hb). Results at Week 2 Reported Here. [ Time Frame: Week 2 ]
    Change from baseline in Hemoglobin (Hb). Results at Week 2 reported here.
  • Change From Baseline in Platelet Count. [ Time Frame: Week 2 ]
    Change from baseline in platelet count. Results at Week 2 reported here.
  • Change From Baseline in Ferritin. [ Time Frame: Week 2 ]
    Change from baseline in ferritin. Results at Week 2 reported here.
  • Change From Baseline in Patient/Parent Global Assessment of Disease Related Pain. [ Time Frame: Week 2 ]
    Assessed on a VAS from no pain (0 mm) to very severe pain (100 mm).
  • Time to Study Drug Discontinuation for Any Reason. [ Time Frame: From Day 1 to Week12 ]
    Time to study drug discontinuation was analyzed using Kaplan-Meier curves. Number of patients with premature study drug discontinuation for any reason is reported here.
  • Time to Study Drug Discontinuation Due to Lack of Efficacy or Progressive Disease. [ Time Frame: From Day 1 to Week12 ]
    Proportion of study drug discontinuation due to lack of efficacy or progressive disease was analyzed using Kaplan-Meier curves. Number of patients discontinuing study drug due to lack of efficacy or progressive disease is reported here.
  • Proportion of Patients Who Have Initiated Tapering of Glucocorticoids. [ Time Frame: From Week 2 to Week12 ]
    Please note no patients were treated with any systemic glucocorticoids at randomization. Hence no results available
  • Proportion of Patients That Have Decreased the Glucocorticoid Dose With at Least 50% From Baseline. [ Time Frame: From Week 2 to Week12 ]
    Please note no patients were treated with any systemic glucocorticoids at randomization. Hence no results available
  • Percentage Decrease of the Glucocorticoid Dose From Baseline. [ Time Frame: From Day 1 to Week12 ]
    Please note no patients were treated with any systemic glucocorticoids at randomization. Hence no results available
  • Proportion of Patients With at Least One Adverse Event. [ Time Frame: From Day 1 to Week 16 ]
    All adverse events collected from start of study treatment up to 28 days after stopping study treatment.
  • Proportion of Patients With at Least One Serious Adverse Event Including Death. [ Time Frame: From Informed consent to Week 16 ]
    Serious adverse events (SAEs) will be collected from informed consent up to 28 days after stopping study treatment.
  • Proportion of Patients With Macrophage Activation Syndrome (MAS). [ Time Frame: From Day 1 to Week 16 ]
    Proportion of patients with Macrophage Activation Syndrome (MAS).
  • Proportion of Patients With Antidrug Antibodies (ADA) Against Anakinra. [ Time Frame: Week 2 ]
    Proportion of patients with antidrug antibodies (ADA) against anakinra.
  • Proportion of Patients With Neutralizing Antibodies. [ Time Frame: Week 2 ]
    Confirmed ADA positive samples will be analyzed for the presence of neutralizing antibodies.
  • Anakinra Serum Pre-dose Concentrations. [ Time Frame: Week 2 ]
    Week 2 reported here.
  • Anakinra Serum Pharmacokinetic Parameters: Cmax, [ Time Frame: Week 12 ]
    PK parameters only available for 2 patients.
  • Anakinra Serum Pharmacokinetic Parameters, Tmax and T½ [ Time Frame: Week 12 ]
    PK parameters only available for 2 patients
  • Anakinra Serum Pharmacokinetic Parameter: AUC 0-24 h [ Time Frame: Week 12 ]
    PK parameters only available for 2 patients
  • Anakinra Serum Pharmacokinetic Parameter: CL/F [ Time Frame: Week 12 ]
    Pharmacokinetic parameters only available for 2 patients
  • Anakinra Serum Pharmacokinetic Parameter: Vd/F [ Time Frame: Week 12 ]
    PK parameters only available for 2 patients
  • Change From Baseline in JADAS27. [ Time Frame: Week 2 ]
    Juvenile Arthritis Disease Activity Score (JADAS) includes 4 measures: physician global assessment of disease activity, patient or parent global assessment of overall well-being, 27 active joint count, and CRP. The JADAS27 includes the 27 joints. JADAS27 is calculated as the sum of its four components, physician global assessment of disease activity converted to cm from the VAS (0=no activity, 10=maximum activity); patient global assessment of well-being converted to cm from the VAS (0=very well, 10=very poor); active joint count (0-27); and CRP. Prior to calculation CRP is truncated to a 0 - 10 scale according to the following formula: (CRP (mg/l) -10)/10. Before calculation, CRP values <10 mg/l are converted to 10 and CRP values >110 mg/l are converted to 110. The JADAS27 tool yields a global score of 0-57. Only results from Week 2 reported here.
  • Number of Days Off School or Work Due to Still's Disease. [ Time Frame: Week 2 ]
    Number of days off school or work due to Still's disease week 1-2.
  • Proportion of Patients With Inactive Disease. [ Time Frame: Week 12 ]
    Inactive disease is a composite of the following parameters: no joints with active arthritis, no fever, no rash, no serositis, no splenomegaly, no generalized lymphadenopathy attributable to Still's disease, CRP level within normal limits, physician's global assessment of disease activity score below 10 mm on a 100 mm VAS and a documented morning stiffness ≤15 minutes.
  • Change From Baseline in IL-6. [ Time Frame: Week 2 ]
    Only results from Week 2 reported here.
  • Change From Baseline in IL-18. [ Time Frame: Week 2 ]
    Only results from Week 2 reported here
  • Change From Baseline in Serum Calprotectin. [ Time Frame: Week 2 ]
    Change from baseline in serum calprotectin. Only results from Week 2 reported here
  • Change From Baseline in Neopterin. [ Time Frame: Week 2 ]
    Only results from Week 2 reported here
Original Secondary Outcome Measures  ICMJE
 (submitted: August 25, 2017)
  • Proportion of ACR30 Responders With Absence of Fever During 24 Hours Preceding Week 1. [ Time Frame: Week 1 ]
    ACR30 response is defined as an improvement of ≥ 30% from baseline in at least 3 of any 6 variables listed in the description of the primary outcome measure. Also no more than 1 of the 6 variables may worsen by >30% from baseline.
  • Proportion of ACR50 Responders With Absence of Fever During 24 Hours Preceding Week 1. [ Time Frame: Week 1 ]
    ACR50 response is defined as an improvement of ≥ 50% from baseline in at least 3 of any 6 variables listed in the description of the primary outcome measure. Also no more than 1 of the 6 variables may worsen by >30% from baseline.
  • Proportion of ACR70 Responders With Absence of Fever During 24 Hours Preceding Week 1. [ Time Frame: Week 1 ]
    ACR70 response is defined as an improvement of ≥ 70% from baseline in at least 3 of any 6 variables listed in the description of the primary outcome measure. Also no more than 1 of the 6 variables may worsen by >30% from baseline.
  • Proportion of ACR90 Responders With Absence of Fever During 24 Hours Preceding Week 1. [ Time Frame: Week 1 ]
    ACR90 response is defined as an improvement of ≥ 90% from baseline in at least 3 of any 6 variables listed in the description of the primary outcome measure. Also no more than 1 of the 6 variables may worsen by >30% from baseline.
  • Proportion of ACR50 Responders With Absence of Fever During 7 Days Preceding Week 2. [ Time Frame: Week 2 ]
    ACR50 response is defined as an improvement of ≥ 50% from baseline in at least 3 of any 6 variables listed in the description of the primary outcome measure. Also no more than 1 of the 6 variables may worsen by >30% from baseline.
  • Proportion of ACR70 Responders With Absence of Fever During 7 Days Preceding Week 2. [ Time Frame: Week 2 ]
    ACR70 response is defined as an improvement of ≥ 70% from baseline in at least 3 of any 6 variables listed in the description of the primary outcome. Also no more than 1 of the 6 variables may worsen by >30% from baseline.
  • Proportion of ACR90 Responders With Absence of Fever During 7 Days Preceding Week 2. [ Time Frame: Week 2 ]
    ACR90 response is defined as an improvement of ≥ 90% from baseline in at least 3 of any 6 variables listed in the description of the primary outcome . Also no more than 1 of the 6 variables may worsen by >30% from baseline.
  • Proportion of Responders in Physician Global Assessment of Disease Activity. [ Time Frame: Day 1, Week 1 and Week 2 ]
    Assessed on a VAS from no disease. activity (0 mm) to very severe disease activity (100 mm). Response is defined as an improvement of ≥ 30%, 50%, 70% and 90% from baseline.
  • Proportion of Responders in Patient/Parent Global Assessment of Overall Well-being. [ Time Frame: Day 1, Week 1 and Week 2 ]
    Assessed on a VAS from very well (0 mm) to very poor. (100 mm). Response is defined as an improvement of ≥ 30%, 50%, 70% and 90% from baseline.
  • Proportion of Responders in Number of Joints With Active Arthritis. [ Time Frame: Day 1, Week 1 and Week 2 ]
    Response is defined as an improvement of ≥ 30%, 50%, 70% and 90% from baseline.
  • Proportion of responders in Number of joints with limitation of movement. [ Time Frame: Day 1, Week 1 and Week 2 ]
    Response is defined as an improvement of ≥ 30%, 50%, 70% and 90% from baseline.
  • Proportion of Responders in Assessment of Physical Function (CHAQ/SHAQ). [ Time Frame: Day 1, Week 1 and Week 2 ]
    Response is defined as an improvement of ≥ 30%, 50%, 70% and 90% from baseline.
  • Proportion of Responders in CRP (mg/L). [ Time Frame: Day 1, Week 1 and Week 2 ]
    Response is defined as an improvement of ≥ 30%, 50%, 70% and 90% from baseline.
  • Proportion of Patients With Absence of Fever During the 7 Days Preceding Week 2. [ Time Frame: Week 2 ]
  • Proportion of Patients With Absence of Fever During the 24 Hours Preceding Week 1. [ Time Frame: Week 1 ]
  • Change From Baseline in Physician Global Assessment of Disease Activity at Week 1. [ Time Frame: Day 1 and Week 1 ]
  • Change From Baseline in Patient/Parent Global Assessment of Overall Well-being at Week 1. [ Time Frame: Day 1 and Week 1 ]
  • Change From Baseline in CRP. [ Time Frame: Day 1 and Week 1 ]
  • Proportion of Patients With Sustained ACR30, ACR50, ACR70 and ACR90 Response. [ Time Frame: Week 2, Week 4, Week 8 and Week 12 ]
    Proportion of patients that still meet the corresponding week 2 response of ACR, with absence of fever in the preceding 7 days.
  • Proportion of patients with sustained ACR30, ACR50, ACR70 and ACR90 response in relation to glucocorticoid tapering. [ Time Frame: Week 2, Week 4, Week 8 and Week 12 ]
    Proportion of patients that still meet the corresponding week 2 response of ACR, with absence of fever in the preceding 7 days, despite glucocorticoid tapering.
  • Proportion of patients with ACR30, ACR50, ACR70 and ACR90 response. [ Time Frame: Week 4, Week 8 and Week 12 ]
  • Proportion of Patients With Absence of Rash. [ Time Frame: Week 1, Week 2, Week 4, Week 8 and Week 12 ]
    Absence of rash is evaluated 24 hours preceding Week 1 and 7 days preceding Week 2, Week 4, Week 8 and Week 12.
  • Change From Baseline in CRP. [ Time Frame: Day 1, Week 1, Week 2, Week 4, Week 8 and Week 12 ]
  • Change from baseline in Hemoglobin (Hb). [ Time Frame: Day 1, Week 1, Week 2, Week 4, Week 8 and Week 12 ]
  • Change From Baseline in Platelet Count. [ Time Frame: Day 1, Week 1, Week 2, Week 4, Week 8 and Week 12 ]
  • Change From Baseline in Ferritin. [ Time Frame: Day 1, Week 1, Week 2, Week 4, Week 8 and Week 12 ]
  • Change From Baseline in Patient/Parent Global Assessment of Disease Related Pain. [ Time Frame: Day 1, Week 1, Week 2, Week 4, Week 8 and Week 12 ]
    Assessed on a VAS from no pain (0 mm) to very severe pain (100 mm).
  • Time to early termination. [ Time Frame: From Day 1 to Week12 ]
    Early termination is defined as an escape or withdrawal due to any reason.
  • Time to early termination due to lack of efficacy or progressive disease. [ Time Frame: From Day 1 to Week12 ]
    Early termination is defined as an escape or withdrawal due to lack of efficacy or progressive disease.
  • Proportion of Patients Who Have Initiated Tapering of Glucocorticoids. [ Time Frame: From Week 2 to Week12 ]
  • Proportion of Patients That Have Decreased the Glucocorticoid Dose With at Least 50% From Baseline. [ Time Frame: From Week 2 to Week12 ]
  • Percentage Decrease of the Glucocorticoid Dose From Baseline. [ Time Frame: From Day 1 to Week12 ]
  • Proportion of Patients With at Least One Adverse Event. [ Time Frame: From Day 1 to Week 16 ]
    All adverse events to be recorded Day 1 until Week 16.
  • Proportion of Patients With at Least One Serious Adverse Event Including Death. [ Time Frame: From Informed consent to Week 16 ]
    Serious adverse events (SAEs) will be collected from informed consent until Week 16.
  • Proportion of Patients With Macrophage Activation Syndrome (MAS). [ Time Frame: From Day 1 to Week 16 ]
  • Proportion of Patients With Antidrug Antibodies (ADA) Against Anakinra. [ Time Frame: Week 1, Week 2, Week 4, Week 8 and Week 12 ]
  • Proportion of Patients With Neutralizing Antibodies. [ Time Frame: Week 1, Week 2, Week 4, Week 8 and Week 12 ]
    Confirmed ADA positive samples will be analyzed for the presence of neutralizing antibodies.
  • Anakinra Serum Pre-dose Concentrations. [ Time Frame: Week 1, Week 2, Week 4, Week 8 and Week 12 ]
  • Anakinra Serum Pharmacokinetic Parameters, Cmax, Tmax, AUClast, AUC0-24h, Vd/F, t½, CL/F. [ Time Frame: Week 12 ]
  • Number of Days Off School or Work Due to Still's Disease. [ Time Frame: Week 1, Week 2, Week 4, Week 8 and Week 12 ]
  • Proportion of Patients With Inactive Disease. [ Time Frame: Week 12 ]
    Inactive disease is a composite of the following parameters: no joints with active arthritis, no fever, no rash, no serositis, no splenomegaly, no generalized lymphadenopathy attributable to Still's disease, CRP level within normal limits, physician's global assessment of disease activity score below 10 mm on a 100 mm VAS and a documented morning stiffness ≤15 minutes.
  • Change From Baseline in JADAS27. [ Time Frame: Week 2 and Week 12 ]
    The JADAS27 includes 4 measures: physician global assessment of disease activity, patient or parent global assessment of overall well-being, 27 active joint count, and CRP.
  • Change From Baseline in IL-6. [ Time Frame: Day 1, Week 1, Week 2, Week 12 ]
  • Change From Baseline in IL-18. [ Time Frame: Day 1, Week 1, Week 2, Week 12 ]
  • Change From Baseline in Serum Calprotectin. [ Time Frame: Day 1, Week 1, Week 2 and Week 12 ]
  • Change From Baseline in Neopterin. [ Time Frame: Day 1, Week 1, Week 2 and Week 12 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate Efficacy and Safety of Anakinra in the Treatment of Still's Disease (SJIA and AOSD)
Official Title  ICMJE A Randomized, Double-blind, Placebo-controlled, Multicenter, Phase 3 Efficacy and Safety Study of 2 Dose Levels of Subcutaneous Anakinra (Kineret®) in Patients With Still's Disease (SJIA and AOSD)
Brief Summary The aim of this study is to demonstrate the efficacy and to evaluate the safety, pharmacokinetics (PK) and immunogenicity of anakinra in patients with newly diagnosed Still's disease, including SJIA (Systemic juvenile idiopathic arthritis) and AOSD (Adult-onset Still's disease).
Detailed Description

The study consists of a 12-week, randomized, double-blind, placebo controlled period with two dose levels of anakinra and a 4-week safety follow-up after last dose of investigational medicinal product (IMP). The primary endpoint will be evaluated at Week 2. Sustained efficacy and time to study drug discontinuation will be evaluated during the full study period.

A screening visit is optional and may be done to identify patients that could be suitable for the study. During the study 6 visits and 2 telephone contacts are scheduled i.e., Day 1 (baseline visit), Day 4Tel, Week 1, Week 2, Week 4, Week 8, Week 12 and Week 16Tel (End of Study).

Patients will be randomly assigned to study drug, after they meet all of the inclusion criteria and none of the exclusion criteria. Patients will receive treatment for 12 weeks, either anakinra or placebo. Patients will be randomized to anakinra in a dose of either 2 or 4 mg/kg/day, with a maximum dose of 100 or 200 mg once daily, respectively. Patients will be randomized to placebo with corresponding volumes for each of the two anakinra dose levels.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Still's Disease, Adult-Onset
  • Still's Disease, Juvenile-Onset
Intervention  ICMJE
  • Biological: anakinra
    sub cutaneous injection
    Other Name: Kineret
  • Drug: Placebo
    sub cutaneous injection
Study Arms  ICMJE
  • Experimental: anakinra
    2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day)
    Intervention: Biological: anakinra
  • Placebo Comparator: Placebo
    Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: June 10, 2019)
13
Original Estimated Enrollment  ICMJE
 (submitted: August 25, 2017)
81
Actual Study Completion Date  ICMJE May 23, 2019
Actual Primary Completion Date February 13, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Signed informed consent.
  2. Male and female patients with a body weight ≥ 10 kg.
  3. Diagnosis of Still's disease.
  4. If currently on glucocorticoid treatment, a stable dose for at least 1 week prior to randomization.
  5. If currently on methotrexate treatment, a stable dose for at least 8 weeks prior to randomization.
  6. Active disease.
  7. Female patients of childbearing potential must use an effective method of contraception during the study (abstinence being a possible option) as well as present a negative pregnancy test prior to randomization.
  8. Negative interferon-gamma release assay or Purified protein derivative ( PPD) test within 2 months prior to randomization. If not available, a test should be performed at day of randomization.

Exclusion Criteria:

  1. Diagnosis of Still's disease more than 6 months prior to randomization.
  2. Previous randomization into this study.
  3. Participation in another concurrent clinical interventional study within 30 days of randomization.
  4. Treatment with an investigational drug within 5 half-lives prior to randomization.
  5. Previous or current treatment with anakinra, canakinumab or any other IL-1 inhibitor.
  6. Use of the following therapies prior to randomization:

    • Narcotic analgesics within 24 hours prior to randomization.
    • Dapsone or etanercept within 3 weeks prior to randomization.
    • Intraarticular, intramuscular or intravenous administration of glucocorticoids or intravenous immunoglobulin (Ig) within 4 weeks prior to randomization.
    • Intravenous Ig with proven Still's disease modifying effect, leflunomide, infliximab or adalimumab within 8 weeks prior to randomization.
    • Thalidomide, cyclosporine, mycophenolate mofetil, 6-mercaptopurine, azathioprine, cyclophosphamide, chlorambucil or any other immunosuppressant within 12 weeks prior to randomization.
    • Tocilizumab within 12 weeks prior to randomization or any other immunomodulatory medication within 4 half-lives prior to randomization
    • Rituximab within 26 weeks prior to randomization.
  7. Live vaccines within 1 month prior to randomization.
  8. Known presence or suspicion of active, chronic or recurrent bacterial, fungal or viral infections, including tuberculosis, HIV infection or hepatitis B or C infection.
  9. Clinical evidence of liver disease or liver injury.
  10. Presence of severe renal function impairment.
  11. Presence of neutropenia.
  12. Presence or suspicion of MAS at baseline.
  13. A diagnosis of MAS within the last 2 months prior to randomization.
  14. History of malignancy within 5 years.
  15. Known hypersensitivity to E coli-derived proteins, or any components of Kineret® (anakinra).
  16. Pregnant or lactating women.
  17. Foreseeable inability to cooperate with given instructions or study procedures.
  18. Presence of any medical or psychological condition or laboratory result that in the opinion of the investigator can interfere with the patient's ability to comply with the protocol requirements or makes the patient not appropriate for inclusion to the study and treatment with IMP.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03265132
Other Study ID Numbers  ICMJE Sobi.ANAKIN-301
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Swedish Orphan Biovitrum
Study Sponsor  ICMJE Swedish Orphan Biovitrum
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Sven Ohlman, MD PhD Swedish Orphan Biovitrum
PRS Account Swedish Orphan Biovitrum
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP