Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Repeated Dose-finding Study of Sarilumab in Children and Adolescents With Systemic Juvenile Idiopathic Arthritis (SKYPS)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02991469
Recruitment Status : Recruiting
First Posted : December 13, 2016
Last Update Posted : October 14, 2019
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi

Tracking Information
First Submitted Date  ICMJE October 14, 2016
First Posted Date  ICMJE December 13, 2016
Last Update Posted Date October 14, 2019
Actual Study Start Date  ICMJE August 9, 2018
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 8, 2018)
  • Assessment of PK parameter: maximum serum concentration observed (Cmax) [ Time Frame: Up to Week 12 ]
  • Assessment of PK parameter: Area under the serum concentration versus time curve calculated using the trapezoidal method during a dose interval (AUC0-t) [ Time Frame: Up to Week 12 ]
  • Assessment of PK parameter: Concentration observed before treatment administration during repeated dosing (Ctrough) [ Time Frame: Up to Week 12 ]
Original Primary Outcome Measures  ICMJE
 (submitted: December 9, 2016)
  • Assessment of PK parameter: maximum serum concentration observed (Cmax) [ Time Frame: Up to Week 12 ]
  • Assessment of PK parameter: Area under the serum concentration versus time curve calculated using the trapezoidal method during a dose interval (AUC0-t) [ Time Frame: Up to Week 12 ]
  • Assessment of PK parameter: Concentration observed before treatment administration during repeated dosing (Ctrough) [ Time Frame: Up to Week 12 ]
  • Assessment of PK parameter: Time to reach maximum serum concentration observed (Tmax) [ Time Frame: Up to Week 12 ]
Change History Complete list of historical versions of study NCT02991469 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 8, 2018)
  • Number of patients with adverse events [ Time Frame: Core treatment phase: Up to Week 12. Extension phase: Up to Week 162 ]
  • Number of patients with local site reactions [ Time Frame: Core treatment phase: Up to Week 12. Extension phase: Up to Week 156 ]
  • Juvenile Idiopathic Arthritis ACR30/50/70/90/100 (in the absence of fever) response rate [ Time Frame: Core treatment phase: Up to Week 12. Extension phase: At weeks 24, 48, and every 24 weeks up to Week 156 ]
  • Change from baseline in JIA ACR component: Physician's global assessment of disease activity [ Time Frame: Core treatment phase: Up to Week 12. Extension phase: At weeks 24, 48, and every 24 weeks up to Week 156 ]
  • Change from baseline in JIA ACR Component: Patient / parent assessment of overall well-being [ Time Frame: Core treatment phase: Up to Week 12. Extension phase: At weeks 24, 48, and every 24 weeks up to Week 156 ]
  • Change from baseline in JIA ACR Component: Childhood Health Assessment Questionnaire (CHAQ) - Disability Index [ Time Frame: Core treatment phase: Up to Week 12. Extension phase: At weeks 24, 48, and every 24 weeks up to Week 156 ]
  • Change from baseline in JIA ACR Component: Number of joints with active arthritis [ Time Frame: Core treatment phase: Up to Week 12. Extension phase: At weeks 24, 48, and every 24 weeks up to Week 156 ]
  • Change from baseline in JIA ACR Component: Number of joints with limitation of motion [ Time Frame: Core treatment phase: Up to Week 12. Extension phase: At weeks 24, 48, and every 24 weeks up to Week 156 ]
  • Change from baseline in JIA ACR Component: High sensitivity C-reactive protein (hs-CRP) [ Time Frame: Core treatment phase: Up to Week 12. Extension phase: At weeks 24, 48, and every 24 weeks up to Week 156 ]
  • Change from baseline in JIA ACR Component: fever [ Time Frame: Core treatment phase: Up to Week 12. Extension phase: At weeks 24, 48, and every 24 weeks up to Week 156 ]
  • Change from baseline in Juvenile Arthritis Disease Activity Score-27 (JADAS) [ Time Frame: Core treatment phase: Up to Week 12. Extension phase: At weeks 24, 48, and every 24 weeks up to Week 156 ]
  • Changes in glucocorticoid use [ Time Frame: Core treatment phase: Up to Week 12. Extension phase: Up to Week 156 ]
  • Changes in IL-6 associated biomarkers: IL6 [ Time Frame: Up to Week 12 ]
  • Changes in IL-6 associated biomarkers: sIL-6R [ Time Frame: Up to Week 12 ]
  • Proportion of patients receiving glucocorticoids by dose category (glucocorticoid equivalent prednisone dose ≥0.5 mg/kg, ≥0.2 mg/kg and <0.5 mg/kg, <0.2 mg/kg) [ Time Frame: At weeks 24, 48, and every 24 weeks up to Week 156 ]
  • Proportion of patients free of glucocorticoids and without JIA flare [ Time Frame: At weeks 24, 48, and every 24 weeks up to Week 156 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 9, 2016)
  • Number of patients with adverse events [ Time Frame: Up to Week 12 ]
  • Number of patients with local site reactions [ Time Frame: Up to Week 12 ]
  • Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30 (ACR30) (in the absence of fever) response rate [ Time Frame: Up to Week 12 ]
  • Change from baseline in JIA ACR component: Physician's global assessment of disease activity [ Time Frame: Up to Week 12 ]
  • Change from baseline in JIA ACR Component: Patient / parent assessment of overall well-being [ Time Frame: Up to Week 12 ]
  • Change from baseline in JIA ACR Component: Childhood Health Assessment Questionnaire (CHAQ) - Disability Index [ Time Frame: Up to Week 12 ]
  • Change from baseline in JIA ACR Component: Number of joints with active arthritis [ Time Frame: Up to Week 12 ]
  • Change from baseline in JIA ACR Component: Number of joints with limitation of motion [ Time Frame: Up to Week 12 ]
  • Change from baseline in JIA ACR Component: High sensitivity C-reactive protein (hs-CRP) [ Time Frame: Up to Week 12 ]
  • Change from Baseline in JIA ACR Component: Erythrocyte Sedimentation Rate (ESR) [ Time Frame: Up to Week 12 ]
  • Changes in IL-6 associated biomarkers: IL6 [ Time Frame: Up to Week 12 ]
  • Changes in IL-6 associated biomarkers: sIL-6R [ Time Frame: Up to Week 12 ]
  • Number of patients with adverse events [ Time Frame: Up to Week 104 ]
  • Number of patients with local site reactions [ Time Frame: Up to Week 104 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Repeated Dose-finding Study of Sarilumab in Children and Adolescents With Systemic Juvenile Idiopathic Arthritis (SKYPS)
Official Title  ICMJE An Open-label, Sequential, Ascending, Repeated Dose-finding Study of Sarilumab, Administered With Subcutaneous (SC) Injection, in Children and Adolescents, Aged 1 to 17 Years, With Systemic Juvenile Idiopathic Arthritis (sJIA), Followed by an Extension Phase
Brief Summary

Primary Objective:

To describe the pharmacokinetic (PK) profile of sarilumab in patients aged 1-17 years with Systemic Juvenile Idiopathic Arthritis (sJIA) in order to identify the dose and regimen for adequate treatment of this population.

Secondary Objective:

To describe the pharmacodynamics (PD) profile, the efficacy, and the long term safety of sarilumab in patients with sJIA.

Detailed Description The total study duration per patient will be 166 weeks that will consist of a 4- week screening, a 12-week core treatment phase, a 144-week extension phase, and a 6-week post-treatment follow-up.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Juvenile Idiopathic Arthritis
Intervention  ICMJE Drug: Sarilumab SAR153191 (REGN88)

Pharmaceutical form: Solution

Route of administration: Subcutaneous

Study Arms  ICMJE Experimental: Sarilumab
Participants will receive one of two ascending doses (or an additional intermediate dose based on available data) of sarilumab by subcutaneous (SC) injection based on body weight. All the participants will receive the selected dose once the selected dose is identified. Sarilumab will be given during 12-week core treatment phase followed by a 144- week extension treatment phase.
Intervention: Drug: Sarilumab SAR153191 (REGN88)
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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 8, 2018)
72
Original Estimated Enrollment  ICMJE
 (submitted: December 9, 2016)
36
Estimated Study Completion Date  ICMJE March 2025
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria :

  • Male and female patients aged ≥1 and ≤17 years (or country specified age requirement, 12-17 years for Russia) at the time of the screening visit.
  • Diagnosis of systemic JIA subtype according to the International Associations against Rheumatism (ILAR) 2001 Juvenile Idiopathic Arthritis (JIA) Classification Criteria with the following features:

    • 5 active joints at screening or
    • 2 active joints at screening with systemic JIA fever >37.5 0C in the 3 days preceding baseline or for at least 3 out of any 7 consecutive days during screening despite glucocorticoids at a dose stable for at least 3 days.
  • Patient with an inadequate response to current treatment and considered as a candidate for a biologic disease modifying anti rheumatic drug (DMARD) as per investigator's judgment.

Exclusion criteria:

  • Body weight <10 kg or >60 kg for patients enrolled in the ascending dose cohorts, then body weight <10 kg for patients subsequently enrolled at the selected dose.
  • Uncontrolled severe systemic symptoms and/or Macrophage Activation Syndrome (MAS) within 6 months prior to screening.
  • History of or ongoing interstitial lung disease, pulmonary hypertension, pulmonary alveolar proteinosis.
  • If nonsteroidal anti-inflammatory drugs (NSAIDs) (including cyclo oxygenase-2 inhibitors [COX-2]) taken, dose stable for less than 2 weeks prior to the baseline visit and/or dosing prescribed outside of approved label.
  • If non-biologic DMARD taken, dose stable for less than 6 weeks prior to the baseline visit or at a dose exceeding the recommended dose as per local labeling.
  • If oral glucocorticoid taken, dose exceeding equivalent prednisone dose 1 mg/kg/day (or 60 mg/day) within 3 days prior to baseline.
  • Use of parenteral or intra-articular glucocorticoid injection within 4 weeks prior to baseline.
  • Prior treatment with anti-interleukin 6 (IL-6) or IL-6 receptor (IL-6R) antagonist therapies, including but not limited to tocilizumab or sarilumab.
  • Treatment with any biologic treatment for sJIA within 5 half-lives prior to the first dose of sarilumab (the required off treatment periods and procedures may vary according to local requirements).
  • Treatment with a Janus kinase inhibitor within 4 weeks prior to the first dose of sarilumab; and treatment with growth hormone within 4 weeks prior to the first dose of sarilumab (the required off treatment periods and procedures may vary according to local requirements).
  • Treatment with any investigational biologic or non-biologic product within 8 weeks or 5 half-lives prior to baseline, whichever is longer.
  • Exclusion related to tuberculosis.
  • Exclusion criteria related to past or current infection other than tuberculosis.
  • Any live, attenuated vaccine within 4 weeks prior to the baseline visit, such as varicella-zoster, oral polio, rubella vaccines. Killed or inactive vaccine may be permitted based on the Investigator's judgment.
  • Exclusion related to history of a systemic hypersensitivity reaction to any biologic drug and known hypersensitivity to any constituent of the product.
  • Laboratory abnormalities at the screening visit (identified by the central laboratory).
  • Severe cardiac disease due to sJIA.
  • Pregnant or breast-feeding female adolescent patients.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: For site information, send an email with site number to Contact-Us@sanofi.com
Listed Location Countries  ICMJE Argentina,   Canada,   Czechia,   Finland,   France,   Germany,   Italy,   Netherlands,   Poland,   Russian Federation,   Spain,   United Kingdom
Removed Location Countries Chile,   Estonia,   United States
 
Administrative Information
NCT Number  ICMJE NCT02991469
Other Study ID Numbers  ICMJE DRI13926
2015-004000-35 ( EudraCT Number )
U1111-1177-3584 ( Other Identifier: UTN )
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 Not Provided
Responsible Party Sanofi
Study Sponsor  ICMJE Sanofi
Collaborators  ICMJE Regeneron Pharmaceuticals
Investigators  ICMJE
Study Director: Clinical Sciences & Operations Sanofi
PRS Account Sanofi
Verification Date October 2019

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