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

Sponsor
Sanofi (Industry)
Overall Status
Recruiting
CT.gov ID
NCT02991469
Collaborator
Regeneron Pharmaceuticals (Industry)
72
Enrollment
30
Locations
1
Arm
103.7
Anticipated Duration (Months)
2.4
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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
  • 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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
72 participants
Allocation:
N/A
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 :
Aug 9, 2018
Anticipated Primary Completion Date :
Jan 1, 2023
Anticipated Study Completion Date :
Apr 1, 2027

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

  1. Assessment of PK parameter: maximum serum concentration observed (Cmax) [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) [Up to Week 12]

  3. Assessment of PK parameter: Concentration observed before treatment administration during repeated dosing (Ctrough) [Up to Week 12]

Secondary Outcome Measures

  1. Number of patients with adverse events [Core treatment phase: Up to Week 12. Extension phase: Up to Week 162]

  2. Number of patients with local site reactions [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 [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 [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 [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 [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 [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 [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) [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 [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) [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 [Core treatment phase: Up to Week 12. Extension phase: Up to Week 156]

  13. Changes in IL-6 associated biomarkers: IL6 [Up to Week 12]

  14. Changes in IL-6 associated biomarkers: sIL-6R [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) [At weeks 24, 48, and every 24 weeks up to Week 156]

  16. Proportion of patients free of glucocorticoids and without JIA flare [At weeks 24, 48, and every 24 weeks up to Week 156]

Eligibility Criteria

Criteria

Ages Eligible for Study:
1 Year to 17 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Investigational Site Number :0320004 Tucumán Argentina T4000AXL
2 Investigational Site Number :1000001 Plovdiv Bulgaria 4000
3 Investigational Site Number :1240110 Calgary Alberta Canada T3B 6A8
4 Investigational Site Number :1240112 Montreal Quebec Canada H3T1C5
5 Investigational Site Number :2030042 Praha 5 - Motol Czechia 15006
6 Investigational Site Number :2460040 Helsinki Finland 00029 HUS
7 Investigational Site Number :2500041 Bron France 69500
8 Investigational Site Number :2500042 Montpellier France 34295
9 Investigational Site Number :2500040 Paris France 75015
10 Investigational Site Number :2760064 Berlin Germany 13125
11 Investigational Site Number :2760065 Berlin Germany 13353
12 Investigational Site Number :2760061 Bremen Germany 28205
13 Investigational Site Number :2760062 Hamburg Germany 22081
14 Investigational Site Number :2760060 Sankt Augustin Germany 53757
15 Investigational Site Number :2760063 Sendenhorst Germany 48324
16 Investigational Site Number :3720001 Dublin Ireland D12 N512
17 Investigational Site Number :3800051 Genova Italy 16147
18 Investigational Site Number :3800054 Milano Italy 20121
19 Investigational Site Number :3800052 Roma Italy
20 Investigational Site Number :6430001 Moscow Russian Federation 115522
21 Investigational Site Number :6430062 Moscow Russian Federation 117198
22 Investigational Site Number :6430063 Moscow Russian Federation 119991
23 Investigational Site Number :6430065 Ufa Russian Federation 450083
24 Investigational Site Number :7240050 Esplugues de Llobregat Catalunya [Cataluña] Spain 08950
25 Investigational Site Number :7240052 Madrid Madrid, Comunidad De Spain 28046
26 Investigational Site Number :7240053 Madrid Spain 28009
27 Investigational Site Number :7240051 Valencia Spain 46026
28 Investigational Site Number :8260031 London London, City Of United Kingdom WC1N 3JH
29 Investigational Site Number :8260034 Leeds United Kingdom LS1 3EX
30 Investigational Site Number :8260033 Liverpool United Kingdom L12 2AP

Sponsors and Collaborators

  • Sanofi
  • Regeneron Pharmaceuticals

Investigators

  • Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Sanofi
ClinicalTrials.gov Identifier:
NCT02991469
Other Study ID Numbers:
  • DRI13926
  • 2015-004000-35
  • U1111-1177-3584
First Posted:
Dec 13, 2016
Last Update Posted:
Jul 6, 2022
Last Verified:
Jul 4, 2022
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Arthritis
Arthritis, Juvenile

Study Results

No Results Posted as of Jul 6, 2022