Combination Therapy for Multisystem Inflammatory Syndrome in Children

(MISTIC Trial)

Recruiting at 1 trial location

Overseen By Adriana Tremoulet, MD, MAS

Age: < 65

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: University of California, San Diego

Disqualifiers: Immunodeficiency, TB, drug allergy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

73 Participants Needed

Trial Summary

What is the purpose of this trial?

In March 2020, children exposed to the virus that causes the COVID-19 illness, SARS-CoV-2, presented with fever and significant inflammation about a month after exposure to the virus. Some children were sick enough to require care in the intensive care unit for what came to be known as Multisystem Inflammatory Syndrome-Children (MIS-C).The clinical presentation shared many features with Kawasaki disease (KD), a self-limited inflammation that can cause ballooning of the arteries of the heart. Thus, physicians reached for many of the therapies used to treat children with KD. Despite the surge of COVID-19 cases and children continuing to present with MIS-C, there are no data that guide the choice of therapy. Thus, the investigators have designed a study to determine which combination of therapies is most effective in helping children with MIS-C recover quickly.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Anakinra for treating Multisystem Inflammatory Syndrome in Children?

Research suggests that early treatment with Anakinra, which helps reduce inflammation, can improve heart-related outcomes in children with this syndrome, even if the disease is severe. ^{1 2 3 4 5}

Is the combination therapy for MIS-C safe for children?

Studies have shown that anakinra and infliximab, used in treating conditions like inflammatory bowel disease and MIS-C, have been evaluated for safety in children. Anakinra has been studied for its safety in treating MIS-C, and infliximab has been used safely in children with inflammatory bowel disease, with methylprednisolone sometimes used to prevent infusion reactions. ^{1 2 4 6 7}

How is the combination drug therapy for MIS-C different from other treatments?

This combination therapy for MIS-C is unique because it includes anakinra, which targets IL-1-mediated inflammation and is used for cases that do not respond to standard treatments like IVIG (intravenous immunoglobulin) and steroids. Anakinra has shown promise in improving cardiac outcomes in MIS-C, making it a novel option for severe or refractory cases. ^{1 2 3 4 8}

Research Team

Adriana H Tremoulet, MD

Principal Investigator

University of California, San Diego

Eligibility Criteria

This trial is for children under 21 with Multisystem Inflammatory Syndrome-Children (MIS-C) after COVID-19 exposure. They must have fever and symptoms from two different systems like heart issues or skin changes, plus lab evidence of inflammation. Kids can't join if they have immune deficiencies or conditions that prevent them from taking the study meds.

Inclusion Criteria

You experience severe stomach pain, diarrhea, nausea, or vomiting.

You have swelling in your lymph nodes (neck or elsewhere).

You have redness and swelling in your eyes, extremities, lips or tongue, or a skin rash.

Exclusion Criteria

You have a weakened immune system.

Pre-existing medical condition that precludes receiving one or more of the study medications (e.g. TB, drug allergy to study medication).

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Initial Treatment

All MIS-C patients are initially treated with IVIG and receive additional therapy if they are severely ill or do not improve clinically.

1 week

Randomized Treatment

Participants are randomized to receive infliximab, steroids, or anakinra as further anti-inflammatory therapy.

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including CRP reduction and left ventricular ejection fraction.

6 weeks

Treatment Details

Interventions

• Anakinra
• Infliximab
• Methylprednisolone

Trial Overview The study tests three treatments for MIS-C: Infliximab, Anakinra, and Methylprednisolone to see which helps kids recover fastest. It's not clear yet which combination works best since this condition is similar to Kawasaki disease but caused by COVID-19.

Participant Groups

Group I: Infliximab Active Control 1 Intervention

Infliximab will be administered as a single IV dose of 10 mg/kg over 2 hours.

Group II: Methylprednisilone (steroids) Active Control 1 Intervention

Methylprednisilone (steroids) will be administered as 2 mg/kg IV or orally divided every 12 hours. At the time of hospital discharge the patient will be given a steroid taper that will take at least 3 weeks to complete.

Group III: Anakinra Active Control 1 Intervention

Anakinra will be administered at a dose of 8 mg/kg/day IV or SQ with 100 mg every 6 hours as the max dose. This is discontinued with a taper during the hospitalization over 2-4 days once a patient is stable with significantly improved clinical course and laboratory profile.

Anakinra is already approved in European Union, United States for the following indications:

Approved in European Union as Kineret for:

• Rheumatoid arthritis
• Cryopyrin-associated periodic syndromes
• Deficiency of interleukin-1 receptor antagonist
• COVID-19

Approved in United States as Kineret for:

• Rheumatoid arthritis
• Deficiency of interleukin-1 receptor antagonist
• Neonatal-onset multisystem inflammatory disease (NOMID)
• COVID-19

Who Is Running the Clinical Trial?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

The Children's Foundation

Collaborator

Trials

1

Recruited

70+

Children's Hospital of Michigan

Collaborator

Trials

26

Recruited

4,200+

Findings from Research

In a study of 82 pediatric patients with refractory multisystemic inflammatory syndrome in children (MIS-C), treatment with anakinra led to significant clinical improvements, with 89.1% of patients discharged without any lasting health issues.

Anakinra was found to be safe for most patients, with no injection site reactions reported; however, elevated liver enzymes were noted in some patients, and there were a few serious cases, including 1.8% mortality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anakinra treatment in multisystemic inflammatory syndrome in children (MIS-C) associated with COVID-19. Çaǧlayan, Ş., Sönmez, HE., Otar Yener, G., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Outcomes of MIS-C patients treated with anakinra: a retrospective multicenter national study. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Early anakinra treatment improves cardiac outcome of multisystem inflammatory syndrome in children regardless of disease severity. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Clinical outcomes and safety of anakinra in the treatment of multisystem inflammatory syndrome in children: a single center observational study. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Anakinra treatment in multisystemic inflammatory syndrome in children (MIS-C) associated with COVID-19. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Multisystem Inflammatory Syndrome in Children - Initial Therapy and Outcomes. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Use of Infliximab Biosimilar Versus Originator in a Pediatric United Kingdom Inflammatory Bowel Disease Induction Cohort. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

The Effectiveness of Methylprednisolone as a Premedication Among the Pediatric Population for Preventing Infusion-Related Reactions to Infliximab. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Interleukin-1 blockade by anakinra improves clinical symptoms in patients with neonatal-onset multisystem inflammatory disease. [2006]