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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitair Medisch Centrum Utrecht

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05], Diseases [C] - Immune System Diseases [C20]

Decision date (initial)

2024-12-13

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

WKZUMCU · ZonMw

External identifiers

EU CT number

2024-518684-35-00

EudraCT number

2015-004393-16

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The main hypothesis of this study is that the (average) number of injections rIL- 1RA per patient in order to achieve and maintain clinically inactive disease in the first year after the start of rIL-1RA, by making additional use of the biomarker IL-18, is lower than the average number of injections rIL-1RA that was necessary per patient in the first year after the start of rIL-1RA in our historical cohort (in which the decision to taper and stop with rIL-1RA was done only on clinical judgment of the treating physician).

Secondary objectives 5

1. * The number of patients with *clinically inactive disease* without medication at time point 1 year.
2. * The total number of disease flares during or after tapering and stop of therapy in the first year;
3. * The number of patients with remission off medication at time point 2 years;
4. * The number of patients needing to switch treatment because of treatment failure during the first year (to calculate reduction in treatment costs)
5. * The number of (serious) adverse events in the first year.

Conditions and MedDRA coding

autoimmune disorders, joint disorders synonym: Still's disease, systemic JIA

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Open label lead-in (observational part): 1. Children and adolescents diagnosed with sJIA (ILAR 2004 classification criteria);
2. 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. 3. Parents or legal guardian (and the subject when age is appropriate) who are willing to sign the consent/assent forms.
4. Intervention part (tapering and stop phase): 1. patients treated with rIL-1RA as first line therapy showing an initial beneficial response (no fever on day 7) to rIL-1RA monotherapy (concomitant NSAID allowed);
5. 2. Achieving at least an ACRPed90 response without fever around point 90 days after start of therapy on rIL-1RA mono therapy (concomitant NSAID allowed).

Exclusion criteria 5

1. Open label lead-in (observational part): 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. 2. Previous systemically administered corticosteroid treatment within 6 weeks before diagnosis and enrollment.
3. 3. Known exclusion criteria for the use of rIL-1RA (renal failure, with a creatinin clearance rate of < 30 ml/min or neutropenia with neutrophil counts of < 1,5 * 10e9/L).
4. Intervention part (tapering and stop phase): 1. An onset of Macrophage Activation Syndrome (MAS) after the diagnosis of sJIA will lead to exclusion of a (potential) subject from participation in this study;
5. 2. Patients with a relapse of sJIA in the open label lead-in phase of the study will be excluded for the tapering and stop phase, and will switch treatment to concomitant corticosteroid treatment and/or other biological therapy (Tocilizumab or Canakinumab) upon the decision of the treating physician.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. * The total (mean/median) number of injections of anakinra per patient necessary to achieve and maintain clinically inactive disease during the first year of treatment.

Secondary endpoints 5

1. * The number of patients with *clinically inactive disease* without medication at time point 1 year.
2. * The total number of disease flares during or after tapering and stop of therapy in the first year;
3. * The number of patients with remission off medication at time point 2 years;
4. * The number of patients needing to switch treatment because of treatment failure during the first year (to calculate reduction in treatment costs)
5. * The number of (serious) adverse events in the first year.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitair Medisch Centrum Utrecht

Sponsor organisation

Universitair Medisch Centrum Utrecht

Address

Heidelberglaan 100

City

Utrecht

Postcode

3584 CX

Country

Netherlands

Scientific contact point

Organisation

Universitair Medisch Centrum Utrecht

Contact name

Dr. S.J. Vaster

Public contact point

Organisation

Universitair Medisch Centrum Utrecht

Contact name

Dr. S.J. Vaster

Locations

1 EU/EEA country · 5 investigational sites

By country

Investigational sites

Results and documents

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

Documents 5 files

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

Application history

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