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

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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

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.


Condition or disease Intervention/treatment Phase
Juvenile Idiopathic Arthritis Drug: Sarilumab SAR153191 (REGN88) Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 72 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : August 9, 2018
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : March 2025


Arm Intervention/treatment
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.
Drug: Sarilumab SAR153191 (REGN88)

Pharmaceutical form: Solution

Route of administration: Subcutaneous





Primary Outcome Measures :
  1. Assessment of PK parameter: maximum serum concentration observed (Cmax) [ Time Frame: Up to Week 12 ]
  2. 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 ]
  3. Assessment of PK parameter: Concentration observed before treatment administration during repeated dosing (Ctrough) [ Time Frame: Up to Week 12 ]

Secondary Outcome Measures :
  1. Number of patients with adverse events [ Time Frame: Core treatment phase: Up to Week 12. Extension phase: Up to Week 162 ]
  2. Number of patients with local site reactions [ Time Frame: Core treatment phase: Up to Week 12. Extension phase: Up to Week 156 ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. 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 ]
  7. 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 ]
  8. 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 ]
  9. 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 ]
  10. 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 ]
  11. 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 ]
  12. Changes in glucocorticoid use [ Time Frame: Core treatment phase: Up to Week 12. Extension phase: Up to Week 156 ]
  13. Changes in IL-6 associated biomarkers: IL6 [ Time Frame: Up to Week 12 ]
  14. Changes in IL-6 associated biomarkers: sIL-6R [ Time Frame: Up to Week 12 ]
  15. 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 ]
  16. Proportion of patients free of glucocorticoids and without JIA flare [ Time Frame: At weeks 24, 48, and every 24 weeks up to Week 156 ]


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Ages Eligible for Study:   1 Year to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02991469


Contacts
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Contact: For site information, send an email with site number to Contact-Us@sanofi.com

  Hide Study Locations
Locations
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Argentina
Investigational Site Number 0320060 Recruiting
Caba, Argentina, C1270AAN
Investigational Site Number 0320004 Recruiting
San Miguel de Tucuman, Argentina, T4000AXL
Canada
Investigational Site Number 1240110 Recruiting
Calgary, Canada, T3B 6A8
Czechia
Investigational Site Number 2030041 Recruiting
Brno, Czechia, 62500
Investigational Site Number 2030040 Recruiting
Praha 2, Czechia, 12808
Investigational Site Number 2030042 Recruiting
Praha 5 - Motol, Czechia, 15006
Finland
Investigational Site Number 2460040 Recruiting
Helsinki, Finland, 00029 HUS
France
Investigational Site Number 2500041 Recruiting
Bron Cedex, France, 69677
Investigational Site Number 2500042 Recruiting
Montpellier, France, 34295
Investigational Site Number 2500040 Recruiting
Paris, France, 75015
Germany
Investigational Site Number 2760064 Recruiting
Berlin, Germany, 13125
Investigational Site Number 2760065 Recruiting
Berlin, Germany, 13353
Investigational Site Number 2760061 Recruiting
Bremen, Germany, 28205
Investigational Site Number 2760062 Recruiting
Hamburg, Germany, 22081
Investigational Site Number 2760060 Recruiting
Sankt Augustin, Germany, 53757
Investigational Site Number 2760063 Recruiting
Sendenhorst, Germany, 48324
Italy
Investigational Site Number 3800051 Recruiting
Genova, Italy, 16147
Investigational Site Number 3800054 Recruiting
Milano, Italy, 20121
Investigational Site Number 3800052 Recruiting
Roma, Italy
Netherlands
Investigational Site Number 5280020 Recruiting
Utrecht, Netherlands, 3584 EA
Poland
Investigational Site Number 6160073 Recruiting
Krakow, Poland, 31-503
Investigational Site Number 6160070 Recruiting
Lublin, Poland, 20-093
Russian Federation
Investigational Site Number 6430001 Recruiting
Moscow, Russian Federation, 115522
Investigational Site Number 6430062 Recruiting
Moscow, Russian Federation, 117198
Investigational Site Number 6430063 Recruiting
Moscow, Russian Federation, 119991
Spain
Investigational Site Number 7240050 Recruiting
Esplugues De Llobregat, Spain, 08950
Investigational Site Number 7240053 Recruiting
Madrid, Spain, 28009
Investigational Site Number 7240052 Recruiting
Madrid, Spain, 28046
Investigational Site Number 7240051 Recruiting
Valencia, Spain, 46026
United Kingdom
Investigational Site Number 8260030 Recruiting
Bristol, United Kingdom, BS2 8BJ
Investigational Site Number 8260034 Recruiting
Leeds, United Kingdom, LS1 3EX
Investigational Site Number 8260033 Recruiting
Liverpool, United Kingdom, L12 2AP
Investigational Site Number 8260031 Recruiting
London, United Kingdom, WC1N 3JH
Sponsors and Collaborators
Sanofi
Regeneron Pharmaceuticals
Investigators
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Study Director: Clinical Sciences & Operations Sanofi

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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT02991469     History of Changes
Other Study ID Numbers: DRI13926
2015-004000-35 ( EudraCT Number )
U1111-1177-3584 ( Other Identifier: UTN )
First Posted: December 13, 2016    Key Record Dates
Last Update Posted: October 14, 2019
Last Verified: October 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Arthritis
Arthritis, Juvenile
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases