Treatment of Macrophage Activation Syndrome (MAS) With Anakinra

• Status: Recruiting
• Trial end date: 2020-10-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Alabama at Birmingham
• Treatments: Interleukin 1 Receptor Antagonist Protein; Methylprednisolone; Methylprednisolone acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate

Criteria

Inclusion Criteria:1] Previous diagnosis of systemic juvenile idiopathic arthritis (sJIA) and fulfills the Ravelli criteria (4) for macrophage activation syndrome with either:

two or more Laboratory criteria: 1. Decreased platelet count (≤262 ×10 9/L) 2. Elevated levels of aspartate aminotransferase (>59 U/L) 3. Decreased white blood cell count (≤4.0 × 109/L) 4. Hypofibrinogenemia (≤2.5 g/L) or, three or more combined clinical/laboratory criteria:

1. Decreased platelet count (≤262 × 109/L)

2. Elevated levels of aspartate aminotransferase (>59 U/L)

3. Decreased white blood cell count (≤4.0 × 109/L)

4. Hypofibrinogenemia (≤2.5 g/L)

5. Central nervous system dysfunction (irritability, disorientation, lethargy, seizures, coma)

6. Hemorrhages (purpura, easy bruising, mucosal bleeding)

7. Hepatomegaly (≥3 cm below the costal margin or confirmed by imaging)

OR

2] No previous diagnosis of sJIA and serum ferritin > 2,000 ng/ml and 3 out of the following:

1. Bicytopenia with two of the following:

1. Absolute Neutrophil Count < 1,000,

2. Platelets < 100, 000/mm3,

3. Hemoglobin < 9 mg/dl

2. Fasting triglyceride >265 mg/dL

3. Splenomegaly

4. ALT OR AST > 120 IU/L (or > 2x upper limit of normal)

5. Fever with temp ≥ 101° F

6. Fibrinogen < 1.5 g/L (150 mg/dl) or INR > 1.5 or d-dimer > 500 ng/ml

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Exclusion Criteria:

1. Evidence of malignancy

2. Culture evidence of systemic bacterial infection at the time of screening

3. Known EBV viremia by PCR at time of screening (positive serologies are not an exclusion; results of EBV testing will not be necessary for enrollment, but may be ordered as part of the standard of care assessment to guide future management as results become available)

4. Previous treatment for the current MAS episode with corticosteroids, anakinra, tocilizumab, anti-TNF therapy or cyclosporine

5. <1 year of age

6. Family history of familial HLH

7. Evidence of any of the following

1. Creatinine at the time of screening > 2X ULN or > twofold increase from patient's baseline creatinine within past 3 months (if known)

2. Albumin < 1.5 at the time of screening

3. Mechanical ventilation at the time of screening

4. Hypotension requiring use of pressors at the time of screening