Clinical Trial Details
— Status: Active, not recruiting
Administrative data
NCT number |
NCT02780583 |
Other study ID # |
F151008003 |
Secondary ID |
FWA00005960SOBI_ |
Status |
Active, not recruiting |
Phase |
Phase 1
|
First received |
|
Last updated |
|
Start date |
May 15, 2016 |
Est. completion date |
April 30, 2024 |
Study information
Verified date |
February 2024 |
Source |
University of Alabama at Birmingham |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
The primary purpose of this study is to determine whether giving injections of anakinra is a
safe and well tolerated treatment to give as an adjunct to standard prescribed treatment for
patients who are admitted to the hospital with signs of severe inflammation (macrophage
activation syndrome) that is potentially life-threatening. Anakinra is a commercially
available product (Kineret™) approved for the treatment of rheumatoid arthritis; it is a
replica of a naturally occurring protein called Il-1 receptor antagonist (IL-1ra), made by
humans to inhibit and regulate the action of interleukin-1 (IL-1). IL-1 is a mediator of
inflammation that when generated in excess amounts by immune system cells can result in
severe dysfunction of multiple organs that can be life-threatening. The specific primary
objectives of the study are to determine if giving anakinra results in no increased infection
complications or mortality. Additional data will be collected to determine whether anakinra
administration results in any other unanticipated side effects in this setting, and the
effects of anakinra administration on inflammation markers, the overall dose of steroids
required to treat the inflammation, and the length of hospital stay.
Description:
Macrophage activation syndrome (MAS) is a disorder whereby the immune system generates very
high levels of substances (cytokines) that promote inflammation to the extent dysfunction
occurs in multiple organ systems which if unchecked, is frequently fatal to the affected
individual. This can occur in the setting of a number of different immune system disorders
including, systemic lupus, systemic-onset juvenile arthritis, and adult-onset Still's
disease. MAS can also occur in response to infection with certain viruses such as
Epstein-Barr virus (EBV) and malignancies involving lymphocytes.
Because of the high fatality of MAS (>50%), a number of different treatments have been tried
to manage this disorder, including use of high-dose steroids, immune suppressants such as
cyclosporine, and cytotoxic chemotherapy treatments (etoposide) with variable success and/or
severe complications of immune suppression (as may occur with etoposide). A number of recent
case reports and case series have reported success using cytokine-blocking therapies such as
anakinra in the treatment of MAS that is associated with systemic-onset juvenile idiopathic
arthritis and adult Still's disease. Anakinra is a bio-engineered form of the naturally
occurring interleukin-1 receptor antagonist (IL-1ra), that blocks the action of
interleukin-1, one of the cytokines that is expressed and present in very high amounts in
patients who have MAS. Anakinra/Il-1ra is an attractive treatment for patients presenting
with clinical features of MAS because it has a relatively short half-life and is easy to
administer by subcutaneous injection. In previous trials of its use in patients with clinical
features of bacterial sepsis (fever, elevated heart rate, low/falling blood pressure) , it
was shown that anakinra does not have a harmful effect but also did not appear to have any
benefit with repect to the defined primary outcome of improved survival. However, a recent
re-analysis of the data accumulated in these same previous sepsis trials (for which the
primary defined outcome was survival) indicates that survival was actually increased in the
subgroup of sepsis patients with features of MAS (ferritin elevations in excess of 2,000
ng/ml, signs of coagulopathy, and liver enzyme elevations) who were randomized to receive
anakinra compared to the subgroup of sepsis patients with features of MAS who were randomized
to receive placebo.
Previous doses of anakinra up to 3500 mg/day over 72 hours that were employed in the trials
of adult patients with sepsis were noted to be well tolerated without increased adverse
outcomes compared to patients randomized to placebo. Recent case reports have shown that
doses up to 100 mg every 6 hours were efficacious and well tolerated in children with
systemic onset juvenile arthritis complicated by refractory macrophage activation syndrome.
This study will be the first controlled study to confirm whether anakinra at dose of 10
mg/kg/day to a maximum of dose of 200 mg/day divided every 12 hours (for children ≤40 kg) or
5 mg/kg/day up to a maximum dose of 400 mg/day divided every 6 hours (children > 40 kg and
adults) does not result in increased mortality or infection complications when administered
in addition to current UAB standard of care treatment (corticosteroids) to children and
adults hospitalized with suspected macrophage activation syndrome.