An open-label, ascending, repeated, dose-finding study of Sarilumab in children and adolescents with polyarticular-course juvenile idiopathic arthritis (pcJIA)

• Register: EUCTR
• Last refreshed on: 19 February 2024
• Main ID: EUCTR2015-003999-79-PL
• Date of registration: 07/07/2016
• Prospective Registration: Yes
• Primary sponsor: sanofi-aventis recherche & développement
• Public title: An open-label, ascending, repeated, dose-finding study of Sarilumab in children and adolescents with polyarticular-course juvenile idiopathic arthritis (pcJIA)
• Scientific title: An Open-label, Sequential, Ascending, Repeated Dose-finding Study of Sarilumab, Administered with Subcutaneous (SC) Injection, in Children and Adolescents, Aged 2 to 17 Years, with Polyarticular-course Juvenile Idiopathic Arthritis (pcJIA) Followed by an Extension Phase
• Date of first enrolment: 22/08/2016
• Target sample size: 72
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-003999-79
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other: Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Canada, Chile, Czech Republic, Estonia, Finland, France, Germany, Italy, Mexico, Netherlands, Poland, Russian Federation, Spain, United Kingdom, United States

Contacts

• Affiliation: Sanofi-Aventis Sp. z o.o.

• Affiliation: Sanofi-Aventis Sp. z o.o.

Key inclusion & exclusion criteria

Inclusion criteria:
-Male and female patients aged =2 and =17 years (or country specified age requirement) at the time of the screening visit.
-Diagnosis of rheumatoid factor-negative or rheumatoid factor positive polyarticular Juvenile Idiopathic Arhtritis (JIA) subtype or oligoarticular extended JIA subtype according to the International League of Associations for Rheumatology (ILAR) 2001 Juvenile Idiopathic Arthritis Classification Criteria with at least 5 active joints as per American College of Rheumatology (ACR) definition for “active arthritis” at screening.
-Patient with an inadequate response to current treatment and considered as a candidate for a biologic disease-modifying antirheumatic drug (DMARD) as per Investigator’s judgment.

Are the trial subjects under 18? yes
Number of subjects for this age range: 72
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
-Body weight <10 kg or >60 kg for patients enrolled in the 3 ascending dose cohorts, then body weight <10 kg for patients subsequently enrolled at the selected dose-regimen.
-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 0.5 mg/kg/day (or 30 mg/day) within 2 weeks 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 DMARD within 5 half-lives prior to the first dose of sarilumab
-Treatment with a Janus kinase inhibitor within 4 weeks prior to the firstdose 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.
-Lipid lowering drug stable for less than 6 weeks prior to screening.
-Exclusion related to tuberculosis (TB).
-Exclusion criteria related to past or current infection other than tuberculosis.
-Any live, attenuated vaccine within 4 weeks prior to the baseline, 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 centrallaboratory).
-Pregnant or breast-feeding female adolescent patients.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Juvenile idiopathic arthritis
MedDRA version: 21.0 Level: PT Classification code 10059176 Term: Juvenile idiopathic arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Name: Sarilumab
Product Code: SAR153191 (REGN88)
Pharmaceutical Form: Solution for injection
INN or Proposed INN: SARILUMAB
Current Sponsor code: SAR153191 (REGN88)
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 175-

Primary Outcome(s)

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

Timepoint(s) of evaluation of this end point: Up to week 12

Main Objective: To describe the pharmacokinetic (PK) profile of sarilumab in patients aged 2-17 years with Polyarticular-course Juvenile idiopathic Arthritis (pcJIA) in order to identify the dose and regimen for continued development in this population.

Primary end point(s): Assessment of PK parameter: maximum serum concentration observed (Cmax)
Assessment of PK parameter: Area under the serum concentration versus time curve calculated using the trapezoidal method during a dose interval (AUC0-t)
Assessment of PK parameter: Concentration observed before treatment administration during repeated dosing (Ctrough)

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1 : Core treatment phase: Up to Week 12 - Extension phase: Up to Week 162
2 : Core treatment phase: Up to Week 12 - Extension phase: Up to Week 156
3-10 : Core treatment phase: Up to Week 12 - Extension phase: At weeks24, 48, and every 24 weeks up to Week 156
11-12: Up to week 12

Secondary end point(s): 1- Number of adverse events
2- Acceptability assessments (local tolerability)
3- Juvenile Idiopathic Arthritis (JIA ACR) 30/50/70/90/100 response rate
4- Change from baseline in JIA ACR Component: Physician's global assessment of disease activity
5- Change from baseline in JIA ACR Component: Patient / parent assessment of overall well-being
6- Change from baseline in JIA ACR Component: Childhood Health Assessment Questionnaire (CHAQ) – Disability Index
7- Change from baseline in JIA ACR Component: Number of joints with active arthritis
8- Change from baseline in JIA ACR Component: Number of joints with limitation of motion
9- Change from baseline in JIA ACR Component: High sensitivity C-reactive protein (hs-CRP)
10- Juvenile Arthritis Disease Activity Score-27 (JADAS) change from baseline
11- Changes in IL-6 associated biomarkers
12- Changes in IL-6 associated biomarkers : sIL-6 R

Secondary ID(s)

2015-003999-79-GB

DRI13925

Source(s) of Monetary Support

sanofi-aventis recherche & développement

Ethics review

Status: Approved
Approval date: 07/07/2016
Contact: