This study has been transitioned to CTIS with ID 2024-518684-35-00 check the CTIS register for the current data. The current project proposal continues on our findings of the performed prospective cohort study, aiming to develop a biomarker guided…
ID
Source
Brief title
Condition
- Autoimmune disorders
- Joint disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
* The total (mean/median) number of injections of anakinra per patient during
the first year of treatment;
Secondary outcome
* The number of patients with *clinically inactive disease* without medication
at time point 1 year.
* 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 2 years;
* The number of patients needing to switch treatment because of treatment
failure during the first year (to calculate reduction in treatment costs)
* The number of (serious) adverse events in the first year.
Background summary
Systemic Juvenile Idiopathic Arthritis (sJIA) is a rare disease, affecting
20-40 new patients in the Netherlands each year. SJIA
is currently classified as a subtype of JIA, characterised by chronic arthritis
as well as signs of systemic (auto-) inflammation.
Until recently, the cornerstone in the treatment of sJIA consisted of
corticosteroids, often necessary in high doses during
prolonged time. This resulted in significant side effects like growth
retardation, hypertension etc.
Since 2005, understanding of the pathophysiology of sJIA has increased, showing
the importance of IL-1 and IL-6 in the
inflammatory cascade of this disease. These findings have resulted in the use
of recombinant IL-1 receptor antagonist (rIL-1RA
or anakinra), still an unregistered drug for this indication, as well as the
registration of tocilizumab (anti-IL-6) in 2011 and
Canakinumab (anti-IL-1) in 2013 for the indication sJIA.
However, Tocilizumab and Canakinumab are registered as 2nd line treatment, for
children with unsatisfactory responses to
corticosteroids. This means that patients with sJIA still suffer from major
side effects of corticosteroids and ultimately many of
these patients need to switch to anti-IL-1 or anti-IL-6 in the chronic phase of
sJIA, when proven steroid dependent. As no
known stop-strategies for these drugs are currently available, these patients
face long-term immunosuppressive treatment at
high costs and uncertain risks.
We recently performed a prospective cohort study, treating new-onset sJIA
patients with r-IL-1RA as first line treatment in
corticosteroid naïve sJIA patients. We showed high response rates and
importantly, also tested a stop-strategy that associated
succesful stopping with low levels of several biomarkers.
Study objective
This study has been transitioned to CTIS with ID 2024-518684-35-00 check the CTIS register for the current data.
The current project proposal continues on our findings of the performed
prospective cohort study, aiming to develop a biomarker guided stop strategy
for the use of rIL-1RA in sJIA: short and targeted therapy early in the disease
course with a yet unregistered drug for sJIA.
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).
Study design
non-randomised, biomarker-driven, tapering and stop study (intervention trial)
Intervention
Tapering and discontinuation of treatment if patients on rIL- 1RA therapy at
D90 (after 3 months of therapy) show a good clinical response (adapted ACRPed
score 90 or clinically inactive disease) and have a biomarker value below the
treshold (IL-18).
Study burden and risks
Concerning burden: nil.
- No extra visits / outpatient visits because of the study (following the
current clinical practice)
- Only iin case blood is drawn because of clinical indication in the first year
after start of therapy, an additional quantity of blood is taken (up to 10
times in the first year) for the determination of the biomarker IL -18
- Standardized and validated questionnaires ( JAMAR ) will be collceted at
multiple time points during the study. These are currently already used in
clinical practice to monitor patient reported disease activity .
Regarding risk : low risk.
- It is a tapering and stop study of a specific biological ( rIL- 1RA). Early
cessation of treatment will have no measurable increased risk for the patient.
Since it can not be excluded that patients show disease activity again after
discontinuation of treatment, there will be close monitoring during the study
in order to be able to start therapy asap again if needed.
Lundlaan 6
Utrecht 3584EA
NL
Lundlaan 6
Utrecht 3584EA
NL
Listed location countries
Age
Inclusion criteria
Open label lead-in (observational part):
1. Children and adolescents diagnosed with sJIA (ILAR 2004 classification criteria);;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. Parents or legal guardian (and the subject when age is appropriate) who are willing to sign the consent/assent forms.;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);
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
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. Previous systemically administered corticosteroid treatment within 6 weeks before diagnosis and enrollment.;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).;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;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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-518684-35-00 |
| EudraCT | EUCTR2015-004393-16-NL |
| CCMO | NL55231.041.16 |