Clinical trial NCT02991469: A Repeated Dose-finding Study of Sarilumab in Children and Adolescents With Systemic Juvenile Idiopathic Arthritis (SKYPS)
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Juvenile Idiopathic Arthritis
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2016-12-13
Enrollment: 72
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Assessment of PK parameter: maximum serum concentration observed (Cmax)
timeFrame: Up to Week 12
measure: Assessment of PK parameter: Area under the serum concentration versus time curve calculated using the trapezoidal method during a dose interval (AUC0-t)
timeFrame: Up to Week 12
measure: Assessment of PK parameter: Concentration observed before treatment administration during repeated dosing (Ctrough)
timeFrame: Up to Week 12
Secondary outcomes:
measure: Number of patients with adverse events
timeFrame: Core treatment phase: Up to Week 12. Extension phase: Up to Week 162
measure: Number of patients with local site reactions
timeFrame: Core treatment phase: Up to Week 12. Extension phase: Up to Week 156
measure: Juvenile Idiopathic Arthritis ACR30/50/70/90/100 (in the absence of fever) response rate
timeFrame: Core treatment phase: Up to Week 12. Extension phase: At weeks 24, 48, and every 24 weeks up to Week 156
measure: Change from baseline in JIA ACR component: Physician's global assessment of disease activity
timeFrame: Core treatment phase: Up to Week 12. Extension phase: At weeks 24, 48, and every 24 weeks up to Week 156
measure: Change from baseline in JIA ACR Component: Patient / parent assessment of overall well-being
timeFrame: Core treatment phase: Up to Week 12. Extension phase: At weeks 24, 48, and every 24 weeks up to Week 156
measure: Change from baseline in JIA ACR Component: Childhood Health Assessment Questionnaire (CHAQ) - Disability Index
timeFrame: Core treatment phase: Up to Week 12. Extension phase: At weeks 24, 48, and every 24 weeks up to Week 156
measure: Change from baseline in JIA ACR Component: Number of joints with active arthritis
timeFrame: Core treatment phase: Up to Week 12. Extension phase: At weeks 24, 48, and every 24 weeks up to Week 156
measure: Change from baseline in JIA ACR Component: Number of joints with limitation of motion
timeFrame: Core treatment phase: Up to Week 12. Extension phase: At weeks 24, 48, and every 24 weeks up to Week 156
measure: Change from baseline in JIA ACR Component: High sensitivity C-reactive protein (hs-CRP)
timeFrame: Core treatment phase: Up to Week 12. Extension phase: At weeks 24, 48, and every 24 weeks up to Week 156
measure: Change from baseline in JIA ACR Component: fever
timeFrame: Core treatment phase: Up to Week 12. Extension phase: At weeks 24, 48, and every 24 weeks up to Week 156
measure: Change from baseline in Juvenile Arthritis Disease Activity Score-27 (JADAS)
timeFrame: Core treatment phase: Up to Week 12. Extension phase: At weeks 24, 48, and every 24 weeks up to Week 156
measure: Changes in glucocorticoid use
timeFrame: Core treatment phase: Up to Week 12. Extension phase: Up to Week 156
measure: Changes in IL-6 associated biomarkers: IL6
timeFrame: Up to Week 12
measure: Changes in IL-6 associated biomarkers: sIL-6R
timeFrame: Up to Week 12
measure: 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)
timeFrame: At weeks 24, 48, and every 24 weeks up to Week 156
measure: Proportion of patients free of glucocorticoids and without JIA flare
timeFrame: At weeks 24, 48, and every 24 weeks up to Week 156
Other outcomes:
Locations:
city: San Miguel de Tucumán
country: Argentina
facility: Investigational Site Number : 0320004
state: Tucumán
city: Plovdiv
country: Bulgaria
facility: Investigational Site Number : 1000001
city: Calgary
country: Canada
facility: Investigational Site Number : 1240110
state: Alberta
city: Montreal
country: Canada
facility: Investigational Site Number : 1240112
state: Quebec
city: Helsinki
country: Finland
facility: Investigational Site Number : 2460040
city: Bron
country: France
facility: Investigational Site Number : 2500041
city: Montpellier
country: France
facility: Investigational Site Number : 2500042
city: Paris
country: France
facility: Investigational Site Number : 2500040
city: Berlin
country: Germany
facility: Investigational Site Number : 2760064
city: Berlin
country: Germany
facility: Investigational Site Number : 2760065
city: Hamburg
country: Germany
facility: Investigational Site Number : 2760062
city: Sankt Augustin
country: Germany
facility: Investigational Site Number : 2760060
city: Sendenhorst
country: Germany
facility: Investigational Site Number : 2760063
city: Dublin
country: Ireland
facility: Investigational Site Number : 3720001
city: Genoa
country: Italy
facility: Investigational Site Number : 3800051
state: Genova
city: Milan
country: Italy
facility: Investigational Site Number : 3800054
state: Milano
city: Rome
country: Italy
facility: Investigational Site Number : 3800052
state: Roma
city: Moscow
country: Russian Federation
facility: Investigational Site Number : 6430001
city: Moscow
country: Russian Federation
facility: Investigational Site Number : 6430062
city: Moscow
country: Russian Federation
facility: Investigational Site Number : 6430063
city: UFA
country: Russian Federation
facility: Investigational Site Number : 6430065
city: Esplugues de Llobregat
country: Spain
facility: Investigational Site Number : 7240050
state: Barcelona [Barcelona]
city: Madrid
country: Spain
facility: Investigational Site Number : 7240053
city: Valencia
country: Spain
facility: Investigational Site Number : 7240051
city: London
country: United Kingdom
facility: Investigational Site Number : 8260031
state: London, City Of
city: Leeds
country: United Kingdom
facility: Investigational Site Number : 8260034
city: Liverpool
country: United Kingdom
facility: Investigational Site Number : 8260033
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: