Clinical Trials Register

Summary
EudraCT Number:	2015-004393-16
Sponsor's Protocol Code Number:	NL55231.041.15
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2016-07-08
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

Netherlands - Competent Authority

A.2

EudraCT number

2015-004393-16

A.3

Full title of the trial

Biomarker-guided treatment-and-stop-strategy for recombinant IL-1receptor antagonist (anakinra) in patients with systemic Juvenile Idiopathic Arthritis.

Biomarker-gestuurde behandelstrategie voor anakinra in systemische Juveniele Idiopathische Arthritis.

A.3.1

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

Biomarker-guided treatment-and-stop-strategy for short acting IL-1 blockade in patients with systemic Juvenile Idiopathic Arthritis.

Biomarker-gestuurde behandelstrategie voor anakinra in systemische Juveniele Idiopathische Arthritis.

A.3.2

Name or abbreviated title of the trial where available

ESTIS trial: Early Stop of targeted Treatment in children with Systemic JIA

A.4.1

Sponsor's protocol code number

NL55231.041.15

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	University Medical Center Utrecht
B.1.3.4	Country	Netherlands
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Netherlands Organisation for Health Research and Develpment ZonMW, Rational Pharmacotherapy program
B.4.2	Country	Netherlands
B.4.1	Name of organisation providing support	Swedish Orphan Biovitrium AB
B.4.2	Country	Sweden
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	University Medical Center Utrecht
B.5.2	Functional name of contact point	BO&O, Bureau Onderzoek & onderwijs
B.5.3	Address:
B.5.3.1	Street Address	Lundlaan 6
B.5.3.2	Town/ city	Utrecht
B.5.3.3	Post code	3584EA
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	31887550871
B.5.6	E-mail	m.musbach@umcutrecht.nl

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	Yes
D.2.1.1.1	Trade name	kineret® or anakinra
D.2.1.1.2	Name of the Marketing Authorisation holder	Swedish Orphan Biovitrum AB
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
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	anakinra / kineret
D.3.2	Product code	not applicable
D.3.4	Pharmaceutical form	Solution for injection in pre-filled syringe
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	ANAKINRA
D.3.9.1	CAS number	143090-92-0
D.3.9.2	Current sponsor code	Anakinra
D.3.9.3	Other descriptive name	rIL-1RA
D.3.9.4	EV Substance Code	SUB05500MIG
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	150
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)	No
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

systemic Juvenile Idiopathic Arthritis

Systemische Jeugdreuma

E.1.1.1

Medical condition in easily understood language

Systemic juvenile idiopathic arthritis

systemische jeugdreuma

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

to develop a biomarker guided treatment and stop strategy for rIL-1RA in systemic Juvenile Idiopathic Arthritis

de ontwikkeling van een biomarker geleide stop strategie voor het gebruik van rIL- 1RA in systemische jeugdreuma

E.2.2

Secondary objectives of the trial

- the total number of disease flares during or after tapering and stop of therapy in the first year
- the number of patients with remission off medication at time point 1 and 2 years
- the total number of injections of anakinra per patient in the first year
- the number of patients needing to switch treatment because of treatment failure during the first year
- the number of (serious) adverse events in the first year.

- Het totale aantal ziekte-relapses tijdens of na het stoppen van de therapie in het eerste jaar
- Het aantal patiënten met een remissie off medicatie op tijdstippen 1 en 2 jaar
- Het totaal aantal injecties van anakinra per patiënt in het eerste jaar
- Het aantal patiënten dat moet switchen van behandeling vanwege non-respons op rIL-1RA gedurende het eerste jaar
- Het aantal (ernstige) bijwerkingen in het eerste jaar.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Children and adolescents diagnosed with sJIA;

2. Both male and female patients, aged 8 months - 16 years (anakinra is approved in children aged 8 months and older who suffer from CAPS, and as per definition, JIA has an onset before the age of 16);

3. Patients treated with anakinra as first line therapy who showed an initial response to anakinra (no fever on day 7);
4. Parents or legal guardian (and the subject when age is appropriate) who are willing to sign the consent/assent forms.

1. Kinderen gediagnosticeerd met systemische JIA;

2. Zowel mannelijke als vrouwelijke patiënten, in de leeftijd van 8 maanden - 16 jaar (anakinra is goedgekeurd bij kinderen van 8 maanden en ouder die last hebben van CAPS, en als per definitie JIA heeft een begin vóór de leeftijd van 16);

3. Patiënten die met anakinra als eerste lijn therapie een initiele goede respons op anakinra tonen (geen koorts meer op dag 7 na starten anakinra)
4. Informed consent van ouders of wettelijke voogd en/of patient bji leeftijd > 12 jaar.

E.4

Principal exclusion criteria

1. An onset of Macrophage Activation Syndrome (MAS) simultaneously with sJIA or after the diagnosis of sJIA will lead to exclusion of a (potential) subject from participation in this study;
2. Previous steroid treatment in the 3 months before diagnosis.

1. Macrofaagactivatiesyndroom (MAS) bij start van de ssystemische JIA of na de diagnose van systemische JIA
2. Eerdere behandeling met steroïden in de 3 maanden voordat de diagnose.

E.5 End points

E.5.1

Primary end point(s)

The number of patients with ‘clinically inactive disease’ without medication at time point 1 year after the start of anakinra (rIL-1RA)

Het aantal patiënten met 'klinisch inactieve ziekte' zonder medicatie op tijdstip 1 jaar na starten van anakinra (rIL-1RA)

E.5.1.1

Timepoint(s) of evaluation of this end point

Time point 1 year after the start of anakinra (rIL-1RA)

Tijdstip 1 jaar na starten van anakinra (rIL-1RA)

E.5.2

Secondary end point(s)

* the total number of disease flares during or after tapering and stop of therapy (rIL-1RA) in the first year;
* the number of patients with remission off medication at time point 1 and 2 years;
* the total number of injections of anakinra per patient;
* the number of patients needing to switch treatment because of treatment failure during the first year
* the number of (serious) adverse events in the first year.

* Het totale aantal ziekte-relapses gedurende of na stoppen van de therapie (rIL-1RA) in het eerste jaar;
* Het aantal patiënten met een remissie off medicatie op tijdstip 1 en 2 jaar;
* Het totale aantal injecties van anakinra per patiënt;
* Het aantal patiënten dat moet switchen van behandeling vanwege ziekte relapse gedurende het eerste jaar
* Het aantal (ernstige) bijwerkingen in het eerste jaar.

E.5.2.1

Timepoint(s) of evaluation of this end point

Time point 1 and 2 years after the start of anakinra (rIL-1RA)

Tijdstip 1 en 2 jaar na starten van anakinra (rIL-1RA)

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

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

Yes

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)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

open-label stop trial

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Children in the age between 8 months and 16 years

Kinderen in de leeftijd tussen 8 maanden en 16 jaar

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

none

geen

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2016-07-08

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-10-04

P. End of Trial
P.	End of Trial Status	Ongoing

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