Clinical Trials Register

Summary
EudraCT Number:	2015-004000-35
Sponsor's Protocol Code Number:	DRI13926
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2016-09-07
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2015-004000-35

A.3

Full title of the trial

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

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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

Studio in aperto, sequenziale, a dosi ripetute, crescenti, per la determinazione della dose di sarilumab, somministrato mediante iniezione sottocutanea (SC), in bambini e adolescenti, di età compresa tra 1 anno e 17 anni, affetti da artrite idiopatica giovanile sistemica (AIGs), seguito da una fase di estensione

A.4.1

Sponsor's protocol code number

DRI13926

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1177-3584

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/067/2013

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	sanofi-aventis recherche & développement
B.1.3.4	Country	France
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	sanofi-aventis recherche & développement
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	sanofi S.p.A.
B.5.2	Functional name of contact point	servizio contract point
B.5.3	Address:
B.5.3.1	Street Address	Viale Bodio, 37/b
B.5.3.2	Town/ city	MILANO
B.5.3.3	Post code	20158
B.5.3.4	Country	Italy
B.5.4	Telephone number	800226343
B.5.5	Fax number	00390239394168
B.5.6	E-mail	informazioni.medicoscientifiche@sanofi.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Sarilumab
D.3.2	Product code	SAR153191 (REGN88)
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	SARILUMAB
D.3.9.2	Current sponsor code	SAR153191
D.3.9.4	EV Substance Code	SUB177914
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	175
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Juvenile Idiopathic Arthritis

Artrite idiopatica giovanile

E.1.1.1

Medical condition in easily understood language

Juvenile Idiopathic Arthritis

Artrite idiopatica giovanile

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.0
E.1.2	Level	PT
E.1.2	Classification code	10059176
E.1.2	Term	Juvenile idiopathic arthritis
E.1.2	System Organ Class	10028395 - Musculoskeletal and connective tissue disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To describe the pharmacokinetic (PK) profile of sarilumab in patients with sJIA in order to identify the dose and regimen for continued development in this population.

E.2.2

Secondary objectives of the trial

To describe:
-The pharmacodynamic (PD) profile, the efficacy and the safety of sarilumab in patients with sJIA.
-The long term safety of sarilumab in patients with sJIA.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

-Male and female patients aged ≥1 and ≤17 years at the time of the screening visit.
-Diagnosis of systemic Juvenile Idiopathic Arthritis (JIA) subtype according to the International Associations against Rheumatism (ILAR) 2001 Juvenile Idiopathic Arthritis Classification Criteria with the following features at screening:
-≥5 active joints at screening or;
-≥2 active joints at screening with systemic JIA fever >37.5 °C in the 3 days preceding baseline or for at least 3 out of any 7 consecutive days during screening despite glucocorticoids at a stable dose for at least 3 days.
-Patients 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.

E.4

Principal exclusion criteria

-Body weight <10 kg or >60 kg.
-Uncontrolled severe systemic symptoms and/or Macrophage Activation Syndrome within 6 months prior to screening.
-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.
-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 first dose of sarilumab.
-Treatment with any Investigational biologic or non-biologic product within 8 weeks or 5 half-lives prior to baseline, whichever is longer.
-Active tuberculosis patients or latent tuberculosis patients without adquate treatment.
-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.

E.5 End points

E.5.1

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)

E.5.1.1

Timepoint(s) of evaluation of this end point

Up to week 12

E.5.2

Secondary end point(s)

1- Number of patients with adverse events
2- Number of patients with local site reactions
3- Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30 (ACR30) response rate
4- Change from baseline in individual JIA ACR components
5- Changes in IL-6 associated biomarkers
6- Number of patients with adverse events
7- Number of patients with local site reactions
8- Change from baseline in individual JIA ACR components

E.5.2.1

Timepoint(s) of evaluation of this end point

1-5: Up to week 12
6-8: Up to week 104

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open