Combination Therapy for Multisystem Inflammatory Syndrome in Children

(MISTIC Trial)

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates the best combination of treatments to help children recover from Multisystem Inflammatory Syndrome in Children (MIS-C), a condition linked to COVID-19. MIS-C can cause symptoms such as fever, stomach issues, and heart problems. The trial tests three treatments: Anakinra (an immunosuppressive drug), Infliximab (a monoclonal antibody), and Methylprednisolone (a corticosteroid). Children who have had COVID-19 or were exposed to the virus, and show symptoms like fever and issues with two different body systems, might be suitable candidates.

As a Phase 2, Phase 3 trial, this research measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering hope for effective recovery options.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that anakinra holds promise for children with MIS-C, improving symptoms such as fever and heart function. Most children tolerated it well, with no major safety concerns reported.

Research has demonstrated that infliximab is safe for children with conditions like Kawasaki disease, which is similar to MIS-C. Infliximab reduced inflammation and improved heart health, with few safety issues noted.

Methylprednisolone, a type of steroid, has been used early in MIS-C treatment. Studies suggest it shortens hospital stays and is generally well-tolerated by children.

Overall, these treatments have demonstrated positive safety profiles in past studies, indicating they are generally safe for children with MIS-C. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for Multisystem Inflammatory Syndrome in Children (MIS-C) because they offer unique approaches compared to standard treatments like intravenous immunoglobulin (IVIG) and aspirin. Anakinra, for example, targets specific inflammatory pathways by blocking the action of interleukin-1, a molecule that plays a significant role in inflammation. Infliximab is a monoclonal antibody that neutralizes tumor necrosis factor-alpha (TNF-alpha), another key player in inflammation, offering a different mechanism than the typical therapies. Methylprednisolone, a corticosteroid, provides a potent anti-inflammatory effect with a structured tapering plan that helps balance immediate relief and long-term management. These diverse mechanisms give researchers hope for more effective and faster-acting treatment options for MIS-C.

What evidence suggests that this trial's treatments could be effective for MIS-C?

This trial will compare the effectiveness of different treatments for children with Multisystem Inflammatory Syndrome (MIS-C). Studies have shown that each treatment in this trial may benefit children with MIS-C. Research indicates that infliximab, especially when combined with IVIG, can improve heart health, reduce inflammation quickly, and shorten ICU stays. Methylprednisolone, another treatment option, works well on its own and can be as effective as when combined with other treatments like IVIG. Anakinra, also under study, has shown good results in improving fever and heart issues, though it might lead to longer hospital stays for some patients. These medicines help manage symptoms by reducing inflammation, a key issue in MIS-C. ^{2 3 6 7 8}

Who Is on the Research Team?

Adriana H Tremoulet, MD

Principal Investigator

University of California, San Diego

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10478576/

Outcomes of MIS-C patients treated with anakinra In this retrospective cohort of severe MIS-C patients treated with anakinra we report favorable clinical outcomes with a low incidence of side effects. The ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10666339/

Impact of anakinra use on clinical outcomes in children ... Of 138 children diagnosed with MIS-C, 79% had moderate or severe illness and 41% received anakinra. Of those, 31 patients who received anakinra ...

3. rheumatologyadvisor.com rheumatologyadvisor.com/home/topics/pediatric-rheumatology/anakinra-linked-to-longer-hospitalization-in-mis-c/

Anakinra Linked to Longer Hospital Stay in Multisystem ... Anakinra use was linked to an extended hospital stay among patients with moderate to severe multisystem inflammatory syndrome in children (MIS- ...

4. ped-rheum.biomedcentral.com ped-rheum.biomedcentral.com/articles/10.1186/s12969-023-00858-z

Clinical outcomes and safety of anakinra in the treatment of ... Anakinra treatment, which was co-administered with IVIG primarily in patients with severe MIS-C, was associated with improvements in fever and cardiac function.

5. acrjournals.onlinelibrary.wiley.com acrjournals.onlinelibrary.wiley.com/doi/10.1002/art.42495

Variation in Early Anakinra Use and Short‐Term Outcomes in ... We identified substantial variation in initial anakinra use in a real-world population of children with MIS-C, but no average short-term ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9433644/

Anakinra treatment in multisystemic inflammatory ... Based on the results of the study, anakinra was associated with clinical improvements and was safe for most patients with refractory MIS-C.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT00069329

Study Details | NCT00069329 | Anakinra to Treat Patients ... This study will evaluate the safety and effectiveness of anakinra (Kineret) for treating patients with neonatal-onset multisystem inflammatory disease (NOMID)

8. acrabstracts.org acrabstracts.org/abstract/outcomes-and-safety-of-anakinra-for-the-treatment-of-multisystem-inflammatory-syndrome-in-children/

Outcomes and Safety of Anakinra for the Treatment ... Conclusion: Treatment of MIS-C with anakinra was associated with resolution of symptoms, including fever and cardiovascular dysfunction, with no significant ...