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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sanofi-Aventis Recherche & Developpement

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

29 Aug 2018 → ongoing

Decision date (initial)

2024-07-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Sanofi-Aventis Recherche & Développement

External identifiers

EU CT number

2024-512701-11-00

EudraCT number

2015-004000-35

WHO UTN

U1111-1177-3584

ClinicalTrials.gov

NCT02991469

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenomic, Safety, Efficacy, Pharmacokinetic, Pharmacodynamic, Dose response

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 objectives 1

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

Conditions and MedDRA coding

Systemic Juvenile Idiopathic Arthritis (sJIA)

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-001045-PIP01-10

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Male and female patients aged ≥1 and ≤17 years (or country specified age requirement, ≥6 to ≤17 years for Russia) at the time of the screening visit.
2. Diagnosis of systemic JIA subtype according to the International Associations against Rheumatism (ILAR) 2001 Juvenile Idiopathic Arthritis (JIA) Classification Criteria OR According to 2024 EULAR/PReS recommendation at Screening.
3. 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 18

1. 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.
2. Uncontrolled severe systemic symptoms and/or Macrophage Activation Syndrome (MAS) within 6 months prior to screening.
3. History of or ongoing interstitial lung disease, pulmonary hypertension, pulmonary alveolar proteinosis.
4. 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.
5. 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.
6. If oral glucocorticoid taken, dose exceeding equivalent prednisone dose 1 mg/kg/day (or 60 mg/day) within 3 days prior to baseline.
7. Use of parenteral or intra-articular glucocorticoid injection within 4 weeks prior to baseline.
8. Prior treatment with anti-interleukin 6 (IL-6) or IL-6 receptor (IL-6R) antagonist therapies, including but not limited to tocilizumab or sarilumab.
9. 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).
10. 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).
11. Treatment with any investigational biologic or non-biologic product within 8 weeks or 5 half-lives prior to baseline, whichever is longer.
12. Exclusion related to tuberculosis.
13. Exclusion criteria related to past or current infection other than tuberculosis.
14. 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.
15. Exclusion related to history of a systemic hypersensitivity reaction to any biologic drug and known hypersensitivity to any constituent of the product.
16. Laboratory abnormalities at the screening visit (identified by the central laboratory).
17. Severe cardiac disease due to sJIA.
18. Pregnant or breast-feeding female adolescent patients.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

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 endpoints 11

1. Number of Adverse events; Core treatment phase: Up to Week 12, Extension phase:Up to Week 162
2. Acceptability assessments (local tolerability); Core treatment phase: Up to Week 12, Extension phase:Up to Week 156
3. Proportion of participants with Investigator Global Assessment (IGA) of disease activity below a defined value on 1-100 VAS scale. Core treatment phase: Up to Week 12 Extension phase:At weeks 24, 48, and every 24 weeks up to Week 156.
4. Proportion of participants with Parent / patient Global Assessment (PGA) of well-being below a defined value on 1-100 VAS scale. Core treatment phase: Up to Week 12 Extension phase:At weeks 24, 48, and every 24 weeks up to Week 156.
5. Assessment of participants with clinically inactive disease (CID). Core treatment phase: Up to Week 12 Extension phase: At weeks 24, 48, and every 24 weeks up to Week 156.
6. Changes in glucocorticoid use. Core treatment phase: Up to Week 12 Extension phase:At weeks 24, 48, and every 24 weeks up to Week 156.
7. Juvenile Idiopathic Arthritis ACR30/50/70/90/100 (in the absence of fever) response rate. Population according to the 2001 ILAR classification. 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 individual JIA ACR components. Population according to the 2001 ILAR classification. 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 Juvenile Arthritis Disease Activity Score-27 (JADAS). Population according to the 2001 ILAR classification. Core treatment phase: Up to Week 12 Extension phase: Up to Week 156.
10. Assessment of participants with disease-related symptoms. Population according to the 2024 EULAR / PReS. At Week 4.
11. Changes in IL-6 associated biomarkers. Population according to the 2001 ILAR classification and the 2024 EULAR / PReS. Up to week 12.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sanofi-Aventis Recherche & Developpement

Sponsor organisation

Sanofi-Aventis Recherche & Developpement

Address

13 Quai Jules Guesde

City

Vitry Sur Seine

Postcode

94400

Country

France

Scientific contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Public contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Third parties 14

Locations

11 EU/EEA countries · 27 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 181 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

13 submissions — initial application plus substantial / non-substantial modifications