Treatment of Macrophage Activation Syndrome (MAS) With Anakinra

NCT02780583 | Terminated Phase 1 DMC

• 3 other identifiers: F151008003FWA00005960SOBI_UAB01
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Macrophage Activation Syndrome

Outcome Measures

Primary Outcomes (1)

• Number of acquired infections, deaths in treatment group vs placebo group

  The primary outcome measure is to determine whether hospital acquired infections or deaths are increased when anakinra is added to corticosteroid use during the first 72 hours of MAS management

  within 72 hours after baseline

Secondary Outcomes (2)

• Normalization of elevations of MAS activity markers in treatment group vs placebo group

  baseline to 72 hours after baseline

• Total corticosteroid use and chemotherapy rescue treatment in anakinra treated group vs placebo treated group

  2 years post enrollment

Study Arms (2)

placebo

PLACEBO COMPARATOR

methylprednisolone intravenously, placebo shots every 6 hours

Drug: placebo

anakinra (Kineret)

EXPERIMENTAL

methylprednisolone intravenously, anakinra shots every 6 hours

Drug: kineret

Interventions

kineret DRUG

anakinra administered subcutaneously every 6 hours x 72 hours along with intravenous methylprednisolone

Also known as: Anakinra

anakinra (Kineret)

placebo DRUG

placebo injection administered every 6 hours along with intravenous methylprednisolone

Also known as: normal saline

placebo

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Decreased platelet count (≤262 × 109/L)
• Elevated levels of aspartate aminotransferase (\>59 U/L)
• Decreased white blood cell count (≤4.0 × 109/L)
• Hypofibrinogenemia (≤2.5 g/L)
• Central nervous system dysfunction (irritability, disorientation, lethargy, seizures, coma)
• Hemorrhages (purpura, easy bruising, mucosal bleeding)
• Hepatomegaly (≥3 cm below the costal margin or confirmed by imaging)
• \] No previous diagnosis of sJIA and serum ferritin \> 2,000 ng/ml and 3 out of the following:
• Bicytopenia with two of the following:
• Absolute Neutrophil Count \< 1,000,
• Platelets \< 100, 000/mm3,
• Hemoglobin \< 9 mg/dl
• Fasting triglyceride \>265 mg/dL
• Splenomegaly

You may not qualify if:

• Evidence of malignancy
• Culture evidence of systemic bacterial infection at the time of screening
• Previous treatment for the current MAS episode with corticosteroids, anakinra, tocilizumab, anti-TNF therapy or cyclosporine
• \<1 year of age
• Family history of familial HLH
• Evidence of any of the following
• Creatinine at the time of screening \> 2X ULN or \> twofold increase from patient's baseline creatinine within past 3 months (if known)
• Albumin \< 1.5 at the time of screening
• Mechanical ventilation at the time of screening
• Hypotension requiring use of pressors at the time of screening

Sponsors & Collaborators

• University of Alabama at Birmingham: lead

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Related Publications (2)

• Cron RQ, Chatham WW. The Rheumatologist's Role in COVID-19. J Rheumatol. 2020 May 1;47(5):639-642. doi: 10.3899/jrheum.200334. Epub 2020 Mar 24. No abstract available.

  PMID: 32209661 DERIVED

• Eloseily EM, Weiser P, Crayne CB, Haines H, Mannion ML, Stoll ML, Beukelman T, Atkinson TP, Cron RQ. Benefit of Anakinra in Treating Pediatric Secondary Hemophagocytic Lymphohistiocytosis. Arthritis Rheumatol. 2020 Feb;72(2):326-334. doi: 10.1002/art.41103. Epub 2019 Dec 26.

  PMID: 31513353 DERIVED

MeSH Terms

Conditions

Macrophage Activation Syndrome

Interventions

Interleukin 1 Receptor Antagonist Protein; Saline Solution

Condition Hierarchy (Ancestors)

Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Walter W Chatham, MD

  University of Alabama Hospital

  PRINCIPAL INVESTIGATOR

• Randall Q Cron, MD

  Children's Hospital of Alabama

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 11, 2016
• First Posted: May 23, 2016
• Study Start: May 15, 2016
• Primary Completion: March 31, 2023
• Study Completion: April 30, 2024
• Last Updated: August 1, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: Dec 31 2020
• Access Criteria: request to investigator

Locations

US (1)