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Completed

NCT Number: NCT05001737

Evaluate Efficacy, Safety and Tolerability, PK and PD of Emapalumab in Children and Adults With MAS in Still's or SLE

The purpose of this study is to assess the safety, tolerability and efficacy of emapalumab in children and adults with macrophage activation syndrome (sHLH/MAS) in Still's disease (including systemic juvenile idiopathic arthritis and adult onset Still's disease) or with sHLH/MAS in systemic lupus erythematous, resenting an inadequate response to high dose glucocorticoid treatment.

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Key information

Conditions

Macrophage Activation Syndrome AOSD Arthritis Arthritis, Juvenile Autoimmune Diseases Connective Tissue Diseases Immune System Diseases Immunoproliferative Disorders Joint Diseases Lupus Erythematosus, Systemic Lymphoproliferative Disorders MAS Musculoskeletal Diseases Rheumatic Diseases SJIA Secondary Hemophagocytic Lymphohistiocytosis Skin and Connective Tissue Diseases Still Disease Systemic Lupus Erythematosus

Age range

6 month–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Universitair Ziekenhuis Leuven, Leuven, Belgium

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About this study

Study NI-0501-14 is a two-cohort trial that enrolls subjects who are diagnosed with sHLH/MAS (MAS being a form of secondary HLH) and who are presenting an inadequate response to high doses of GCs. These subjects will be enrolled in 2 cohorts as per their background disease. The cohorts are defined as follows:

  • Cohort 1: MAS in the context of sJIA and AOSD.
  • Cohort 2: MAS in the context of pediatric and adult SLE.

The study has the objectives to investigate the efficacy, safety and tolerability, for 8 weeks, and PK and PD, QoL and immunogenicity in these 2 cohorts for up to 1 year after last dose of of emapalumab.

Macrophage Activation Syndrome (MAS) Secondary Hemophagocytic Lymphohistiocytosis (sHLH) systemic Juvenile Idiopathic Arthritis (sJIA) Adult-onset Still's Disease (AOSD) Systemic Lupus Erythematosus (SLE)

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Run-in phase in all cohorts

  • Informed consent provided by the subject or by the subject s' legally authorized representative(s) with the assent of subjects who are legally capable of providing it, as required by local law.
  • Male and female subjects aged between 6 months and 80 years of age at the time of diagnosis of MAS.
  • MAS defined as per the criteria defined below for each cohort and requiring treatment with GCs.

Interventional phase in all cohorts

  • Informed consent provided by the subject or by the subject's legally authorized representative(s) with the assent of subjects who are legally capable of providing it, as as required by local law.
  • Male and female subjects aged between 6 months and 80 years of age at the time of diagnosis of active MAS.
  • Subjects who have shown an inadequate response to high dose intravenous (i.v.) GCs administered for at least 3 days according to local standard clinical practice, including but not limited to pulses of 30 mg/kg PDN on 3 consecutive days. High i.v. GCs dose is recommended not to be lower than 2 mg/kg/ day PDN equivalent (or at least 60 mg/day in pediatric subjects of 30 kg or more, and at least 1g/day in adult MAS subjects). In case of rapid worsening of the subject's condition and/or laboratory parameters, as per Investigator judgment, inclusion may occur within less than 3 days from starting high dose GCs.
  • Diagnosis of active MAS confirmed by the treating rheumatologist, having ascertained the followings:

a. Febrile subjects presenting with ferritin > 684 ng/mL. b. and any 2 of: i. Platelet count ≤ 181 x109/L ii. AST-level > 48 U/L iii. Triglycerides > 156 mg/dL iv. Fibrinogen level ≤ 360 mg/dL

  • Female subjects of child-bearing potential willing to use highly effective methods of contraception from study drug initiation to 6 months after the last dose of study drug.

Specific inclusion criteria to Cohort 1 and Cohort 2

  • Cohort 1:
  • Confirmed sJIA diagnosis. For subjects presenting with MAS in the context of the onset of sJIA, high presumption of sJIA will suffice for eligibility.
  • Confirmed diagnosis of AOSD as per Yamaguchi criteria.
  • Cohort 2:
  • Confirmed diagnosis of SLE as per SLICC'12 criteria.

Exclusion criteria

  • Primary HLH documented by either the presence of a known causative genetic mutation or abnormal perforin expression and CD107a degranulation assay as described with primary hemophagocytic lymphohistiocytosis or by the presence of family history.
  • Confirmed malignancy. Note: subjects with a suspected malignancy should have mononuclear cells typed by flow cytometry and/or tissue biopsy, as applicable, to rule out malignancy.
  • Treatment with canakinumab, JAK inhibitors, TNF inhibitors and tocilizumab at the time of emapalumab initiation.
  • Ongoing treatment with anakinra at a dose above 4 mg/kg at time of emapalumab initiation.
  • Subjects treated with etoposide for MAS in the last 1 month.
  • Clinically active mycobacteria (typical and atypical), Histoplasma Capsulatum, or Salmonella infections.
  • Evidence of leishmania infections.
  • Evidence of latent tuberculosis.
  • History of hypersensitivity or allergy to any component of the study drug.
  • Receipt of a Bacillus Calmette-Guerin (BCG) vaccine within 12 weeks prior to screening.
  • Receipt of a live or attenuated live (other than BCG) vaccine within 4 weeks prior to screening.
  • Pregnancy or lactating female subjects.

Treatment and study plan

Emapalumab

Drug

Emapalumab iv infusion

Other names: NI-0501, emapalumab-lzsg, ATC code: L04AA39 (WHO)

Primary outcomes

  1. Proportion of Subjects With Complete Response (CR) at Week 8 After First Administration of Emapalumab

    Time frame: 8 weeks

    Resolution of clinical signs and symptoms present at baseline: The macrophage activation syndrome (MAS) clinical activity will be measured on a visual analog scale (VAS) 10 cm.

    Resolution of clinical signs and symptoms present at baseline: The MAS clinical activity will be measured on a visual analog scale (VAS) 10 cm. Clinical signs will be considered as resolved if VAS is below or equal to 1/10.

    And

    Normalization of laboratory parameters relevant to MAS, as follows:

    WBC above LLN, platelet count above LLN, LDH below 1.5 ULN, ALT below 1.5 ULN, AST below 1.5 ULN, fibrinogen higher than 100 mg/dL, ferritin levels decreased by at least 80 % from values at screening or baseline (whichever is higher) or below 2000 ng/ml, whichever is lower

Secondary outcomes

  1. Number of Patients With Glucocorticoids (GC)s Tapering to a Dose Below 50% of Prednisolone (PDN) Equivalent at the Time of Emapalumab Start or to the Same (or Lower) Dose Being Administered Before the Occurrence of MAS Whichever Occurs First

    Time frame: At any time within the first 8 weeks from start of emapalumab treatment

    GC tapering as per investigator discretion

  2. Number of Patients With GCs Tapering to ≤1mg/kg/Day of PDN Equivalent at Any Time Until End of Study (EOS).

    Time frame: At any time in the study, up to 1 year

    GC tapering as per investigator discretion

  3. Time to Achieve GCs Tapering

    Time frame: At any time in the study, up to 1 year

    Median time to achieve GCs tapering to a dose < 50 % of PDN equivalent at the time of emapalumab start or to the same (or lower) dose being administered before the occurrence of MAS (in patients already treated for the underlying condition), or to ≤1mg/kg/Day of PDN Equivalent, whichever occurs first at any time during the study GC tapering as per investigator discretion

  4. Time to First Complete Response (CR)

    Time frame: At any time in the study, up to 1 year

    Time to CR until EOS Resolution of clinical signs and symptoms present at baseline: The MAS clinical activity was measured on a visual analog scale (VAS) 10 cm.

    Definition of CR:

    Resolution of clinical signs and symptoms present at baseline: MAS clinical activity was measured on a 10-cm VAS. Clinical signs were considered resolved if VAS was below or equal to 1/10.

    and

    Normalization of laboratory parameters relevant to MAS as follows:

    • WBC >LLN.
    • Platelet count >LLN.
    • LDH <1.5 ULN.
    • ALT <1.5 ULN.
    • AST <1.5 ULN.
    • Fibrinogen >100 mg/dL.
    • Ferritin levels decreased by at least 80% from values at Screening or baseline (whichever was higher) or <2000 ng/mL, whichever was lower.

  5. Proportion of Subjects With Overall Response as Defined by CR or Partial Response (PR)

    Time frame: At week 8

    Resolution of clinical signs and symptoms present at baseline: The MAS clinical activity was measured on a visual analog scale (VAS) 10 cm.

    CR:

    Resolution of clinical signs and symptoms present at baseline: MAS clinical activity was measured on a 10-cm VAS. Clinical signs were considered resolved if VAS was below or equal to 1/10.

    and

    Normalization of laboratory parameters relevant to MAS as follows:

    • WBC >LLN.
    • Platelet count >LLN.
    • LDH <1.5 ULN.
    • ALT <1.5 ULN.
    • AST <1.5 ULN.
    • Fibrinogen >100 mg/dL.
    • Ferritin levels decreased by at least 80% from values at Screening or baseline (whichever was higher) or <2000 ng/mL, whichever was lower.

    PR:

    Resolution or improvement in clinical signs and symptoms measured by the MAS clinical activity on the VAS. The patient was classified as PR if he or she presented a VAS <4/10.

    and Normalization of at least 3 of the abnormal baseline laboratory parameters relevant to MAS, as defined above.

  6. Time to First Overall Response as Defined by CR or PR

    Time frame: At any time in the study, up to 1 year

    Time to first overall response

    CR:

    Resolution of clinical signs and symptoms present at baseline: MAS clinical activity was measured on a 10-cm VAS. Clinical signs were considered resolved if VAS was below or equal to 1/10.

    and

    Normalization of laboratory parameters relevant to MAS as follows:

    • WBC >LLN.
    • Platelet count >LLN.
    • LDH <1.5 ULN.
    • ALT <1.5 ULN.
    • AST <1.5 ULN.
    • Fibrinogen >100 mg/dL.
    • Ferritin levels decreased by at least 80% from values at Screening or baseline (whichever was higher) or <2000 ng/mL, whichever was lower.

    PR:

    Resolution or improvement in clinical signs and symptoms measured by the MAS clinical activity on the VAS. The patient was classified as PR if he or she presented a VAS <4/10.

    and Normalization of at least 3 of the abnormal baseline laboratory parameters relevant to MAS, as defined above.

  7. MAS Recurrence at Anytime After Achievement of CR

    Time frame: At any time after CR, up to 1 year

    Number of patients with MAS recurrence at anytime after achievement of CR

  8. Withdrawal From the Study Due to Lack of Response

    Time frame: At any time in the study, up to 1 year

    Number of patients withdrawn from the study due to lack of response as per Investigator decision

  9. Survival

    Time frame: At end of study, 1 year

    Number of patients alive at the end of study

Other outcomes

  1. Adverse Events (AEs) (Serious and Non-serious).

    Time frame: At any time in the study, up to 1 year

    number of patients that experienced at least one AE (serious and non-serious).

  2. Study Interruption Due to Safety Reasons

    Time frame: At any time in the study, up to 1 year

    Number of participants withdrawn from study treatment due to adverse event

  3. Laboratory Parameters

    Time frame: At any time in the study, up to 1 year

    Number of patients with clinically meaningful changes in hematology and chemistry laboratory parameters from baseline

  4. Patient Reported Outcomes : PedsQL™;

    Time frame: Baseline, week 8, 6 months, and EOS (1 year)

    Pediatric Quality of Life Inventory (PedsQL™; Generic Core Scales and Infant Scales, Acute versions)

    The PedsQL is scored on a 5-point Likert scale from: 0 (Never) to 4 (Almost always) Then, for ease of interpretability, items are reversed scored and linearly transformed to a 0-100 scale, so that higher scores indicate better HRQOL (Health-Related Quality of Life).

    To reverse score, transform the 0-4 scale items to 0-100 as follows: 0=100, 1=75, 2=50, 3=25, 4=0

    To create the Total Scale Score, the mean is computed as the sum of all the items over the number of items answered on all the Scales (this also accounts for missing data).

    If more than 50% of the items in the scale are missing, the Scale Scores should not be computed.

    If 50% or more items are completed: Impute the mean of the completed items in a scale

  5. Patient Reported Outcomes: Clinician Global Impression of Severity

    Time frame: Baseline, Week 8, month 6 and EOS (1 year)

    Health-related quality of life: Global Assessment: Clinician Global Impression of Severity Number of patients having an overall severity of the health status over the past week assessed by the clinician as None, Mild, Moderate, or Severe, at the specified timepoints.

  6. Patient Reported Outcomes: Patient/Parent Global Impression of Severity

    Time frame: Screening, Week 8, month 6 and EOS (1 year)

    Health-related quality of life: Global Assessment: Patient/Parent Global Impression of Severity

    Number of patients having an overall severity of the health status over the past week assessed by the Patient/Parent as None, Mild, Moderate, or Severe, at the specified timepoints.

  7. PK Endpoints

    Time frame: Baseline (Day 1), week 8, Day 60, Day 100, 6 Months, EOS (1 year)

    Serum concentrations of emapalumab vs. time

  8. PD Endpoints Per Cohort: Chemokines

    Time frame: Baseline, week 8, 6 months, EOS (1 year)

    Levels of the main IFN-γ-induced chemokine (CXCL9).

  9. PD Endpoints Per Cohort: sCD25)

    Time frame: Baseline, week 8, 6 months, EOS (1 year)

    Levels of MAS markers; sCD25 (Soluble CD25 (i.e., soluble IL-2 receptor))

  10. Immunogenicity Endpoints

    Time frame: At any time in the study, up to 1 year

    Occurrence of ADAs to emapalumab until EOS (1 year after last dose of emapalumab) Baseline and overall incidence

Sponsors and collaborators

Lead sponsor

Swedish Orphan Biovitrum

Industry

Registry information

Official study title

A Two-cohort, Open-label, Single Arm, Multicenter Study to Evaluate Efficacy, Safety and Tolerability, PK and PD, of Emapalumab in Children and Adults With MAS in Still's Disease or With MAS in Systemic Lupus Erythematous

Acronym: EMERALD

Important dates

Study start
2021
Primary completion
2024
Study completion
2025
First posted
Aug 12, 2021
Registry last updated
Feb 19, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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