Emapalumab for MAS in Still's Disease or Lupus

(EMERALD Trial)

No longer recruiting at 53 trial locations

Overseen By Anna Westerdahl

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Swedish Orphan Biovitrum

Must be taking: Glucocorticoids

Must not be taking: Canakinumab, JAK inhibitors

Disqualifiers: Primary HLH, Malignancy, Active infections, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 68

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called emapalumab (also known as Gamifant) to determine its safety and effectiveness for people with macrophage activation syndrome (MAS), a severe immune condition. MAS can occur in individuals with Still's disease, including systemic juvenile idiopathic arthritis and adult-onset Still's disease, or with lupus, especially when other treatments have been ineffective. Participants should have MAS that hasn't improved with high doses of steroids, a common medication. The study aims to assist those who frequently experience symptoms like fever, high ferritin levels, and low platelet counts. As a Phase 3 trial, this treatment represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking advancements in MAS treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications like canakinumab, JAK inhibitors, TNF inhibitors, tocilizumab, and high doses of anakinra before starting emapalumab. If you're on etoposide for MAS, you must have stopped it at least a month before joining the trial.

Is there any evidence suggesting that emapalumab is likely to be safe for humans?

Research has shown that emapalumab is generally well-tolerated and effectively controls excessive inflammation. The FDA has already approved it for treating macrophage activation syndrome (MAS), indicating a good safety record based on previous evidence.

In earlier studies, some patients experienced side effects, but these were usually manageable. Common side effects include mild infections and reactions at the injection site. Serious side effects are rare, suggesting that emapalumab is safe for use in patients with similar conditions. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about emapalumab because it offers a new approach to treating macrophage activation syndrome (MAS) in Still's disease and lupus. Unlike existing treatments, which often involve corticosteroids or immunosuppressants, emapalumab specifically targets and inhibits interferon gamma, a key player in the inflammatory process of these diseases. This targeted action not only promises to be more effective in controlling the severe inflammation seen in MAS but also aims to reduce the reliance on broad-spectrum treatments that can have significant side effects. By focusing on a specific pathway, emapalumab could lead to faster and more precise relief for patients.

What evidence suggests that emapalumab might be an effective treatment for MAS in Still's disease or lupus?

Research has shown that emapalumab can help treat macrophage activation syndrome (MAS). In individuals with Still's disease, including systemic juvenile idiopathic arthritis and adult-onset Still's disease, emapalumab has successfully induced remission. It reduced or eliminated MAS symptoms when other treatments failed. Emapalumab blocks interferon-gamma (IFNγ), a substance involved in causing inflammation. For those who haven't improved with high-dose glucocorticoids, emapalumab offers a promising alternative. Participants in this trial will join a single treatment arm, including individuals with MAS in the context of systemic juvenile idiopathic arthritis, adult-onset Still's disease, or systemic lupus erythematosus (SLE). ^{1 2 3 4 6}

Who Is on the Research Team?

Brian Jamieson, MD

Principal Investigator

Swedish Orphan Biovitrum

Are You a Good Fit for This Trial?

This trial is for children and adults aged 6 months to 80 years with macrophage activation syndrome (MAS) in Still's disease or systemic lupus erythematosus (SLE), who haven't responded well to high-dose steroids. Participants must meet specific criteria including fever, low platelets, high liver enzymes, and others. Pregnant women, those with certain infections or allergies to the study drug, or recent recipients of live vaccines cannot join.

Inclusion Criteria

Confirmed diagnosis of AOSD as per Yamaguchi criteria.

I am willing to use effective birth control from the start of the study until 6 months after the last dose.

Cohort 1:

Exclusion Criteria

My cancer diagnosis has been confirmed.

Pregnancy or lactating female subjects.

I am not taking canakinumab, JAK inhibitors, TNF inhibitors, or tocilizumab when starting emapalumab.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive emapalumab for 8 weeks to assess efficacy, safety, and tolerability

8 weeks

Every treatment visit until week 8

Follow-up

Participants are monitored for safety, efficacy, and other outcomes up to 1 year after the last dose

1 year

Day 60, Day 100, 6 months, 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Emapalumab

Trial Overview The trial tests Emapalumab's safety and effectiveness in treating MAS associated with Still's disease or SLE when standard steroid treatments fail. It involves patients receiving Emapalumab under controlled conditions to see if it improves their symptoms compared to previous treatments.

How Is the Trial Designed?

Group I: Cohort 1 (sJIA and AOSD) and Cohort 2 (SLE) Experimental Treatment 1 Intervention

MAS in the context of systemic juvenile idiopathic arthritis and adult onset Still's disease (sJIA and AOSD) or SLE

Emapalumab is already approved in United States for the following indications:

Approved in United States as Gamifant for:

• Primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent or progressive disease or intolerance with conventional HLH therapy

Who Is Running the Clinical Trial?

Swedish Orphan Biovitrum

Lead Sponsor

Trials

103

Recruited

13,300+

Dr. Guido Oelkers

Swedish Orphan Biovitrum

Chief Executive Officer since 2017

PhD in Economics

Dr. Lydia Abad-Franch

Swedish Orphan Biovitrum

Chief Medical Officer since 2023

MD, MBA

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05001737

Study Details | NCT05001737 | Evaluate Efficacy, Safety ... The purpose of this study is to assess the safety, tolerability and efficacy of emapalumab in children and adults with macrophage activation syndrome ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11671904/

Efficacy and safety of therapies for Still's disease and ... IL-1i and IL-6Ri show the highest level of efficacy in the treatment of Still's disease. For MAS, IL-1 and interferon-γ inhibition appear to be effective.

3. ard.bmj.com ard.bmj.com/content/82/6/857

Efficacy and safety of emapalumab in macrophage activation ... Neutralisation of IFNγ with emapalumab was efficacious in inducing remission of MAS secondary to sJIA or AOSD in patients who had failed high-dose ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03311854

NCT03311854 | A Study to Investigate the Safety and ... The purpose of this study is to assess the safety, tolerability and efficacy of emapalumab in sJIA or AOSD participants developing MAS.

5. sobi.com sobi.com/en/press-releases/fda-approves-gamifantr-emapalumab-lzsg-first-ever-treatment-adults-and-children-macrophage-activation-syndrome-stills-disease-2342991

FDA approves Gamifant® (emapalumab-lzsg) as first-ever ... Approval based on the pooled analysis of our pivotal EMERALD and NI-0501-06 studies, showing 54% of patients treated with Gamifant achieved ...

6. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1676749/full

Low-dose emapalumab treatment in refractory ... This study aimed to investigate the efficacy and safety of low-dose emapalumab for patients with refractory MAS in the Chinese population.