A Study to Investigate the Safety and Efficacy of Emapalumab, an Anti-IFN-gamma mAb in Patients With Systemic Juvenile Idiopathic Arthritis (sJIA) or Adult-onset Still's Disease (AOSD) Developing Macrophage Activation Syndrome/Secondary HLH (MAS/sHLH)
Condition: Macrophage Activation Syndrome; Lymphohistiocytosis, Hemophagocytic; Arthritis, Juvenile; Adult Onset Still Disease
MeSH terms: Arthritis; Arthritis, Juvenile; Still's Disease, Adult-Onset; Lymphohistiocytosis, Hemophagocytic; Macrophage Activation Syndrome; Syndrome
Intervention: Emapalumab
Intervention description: Emapalumab was administered at an initial dose of 6 mg/kg by intravenous infusion. Emapalumab treatment continued at a dose of 3 mg/kg, every 3 days until study day 15, and then twice-a-week for an additional 2 weeks, i.e., until study day 28. The emapalumab regimen could be adapted (the frequency between infusions shortened, the dose increased, or the treatment prolonged beyond 4 weeks) upon assessment of a favourable benefit-risk profile. There was a 4-week off-drug follow-up period (up to Week 8).
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 14.0
Sex: All
Minimum age: 0 Years
Healthy volunteers: No
Keywords: Emapalumab; Gamifant; Macrophage activation syndrome; Secondary hemophagocytic lymphohistiocytosis; Interferon-gamma; Systemic juvenile idiopathic arthritis; Adult-onset Still's disease; MAS; HLH; sHLH; IFN-gamma; IFNγ; sJIA; AOSD; NI-0501-06; NI-0501

Summary:

      Macrophage Activation Syndrome (MAS) is a rare, life-threatening condition characterized by
      uncontrolled hyperinflammation which may develop on the background of systemic Juvenile
      Idiopathic Arthritis (sJIA) or Adult-onset Still's Disease (AOSD). Emapalumab is a monoclonal
      antibody neutralizing interferon-gamma (IFN-gamma), a key cytokine which contributes to the
      inflammation and tissue damage seen in MAS. The purpose of this study is to assess the
      safety, tolerability and efficacy of emapalumab in sJIA or AOSD participants developing MAS,
      presenting an inadequate response to high dose glucocorticoid treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients of both genders

          -  For sJIA patients: Confirmed sJIA diagnosis. For patients presenting with MAS in the
             context of the onset of sJIA, high presumption of sJIA will suffice for eligibility.
             For AOSD patients: confirmed AOSD diagnosis as per Yamaguchi criteria.

          -  Diagnosis of active MAS.

          -  An inadequate response to high dose i.v. glucocorticoid treatment administered for at
             least 3 days as per local standard of care (including but not limited to pulses of 30
             mg/kg PDN on 3 consecutive days). High dose i.v. glucocorticoid should not be lower
             than 2 mg/kg/day of PDN equivalent in 2 divided doses (or at least 60 mg/day in
             patients of 30 kg or more). In case of rapid worsening of the patient's condition
             and/or lab parameters, inclusion may occur within less than 3 days from starting high
             dose i.v. glucocorticoids.

          -  Tocilizumab, TNF inhibitors and canakinumab, if administered, have to be discontinued
             before emapalumab initiation.

          -  Having received guidance on contraception for both male and female patients sexually
             active and having reached puberty. Females of child-bearing potential require use of
             highly effective contraceptive measures. Males with partners(s) of child-bearing
             potential must agree to take appropriate precautions.

          -  Informed consent provided by the patient (as required by local law), or by the
             patient's legally authorized representative(s) with the assent of patients who are
             legally capable of providing it, as applicable.

        Exclusion Criteria:

          -  Diagnosis of suspected or confirmed primary HLH or HLH consequent to a neoplastic
             disease.

          -  Active mycobacteria (typical and atypical), Histoplasma Capsulatum, Shigella,
             Salmonella, Campylobacter and Leishmania infections.

          -  Clinical suspicion of latent tuberculosis.

          -  Positive serology for HIV antibodies.

          -  Presence of malignancy.

          -  Patients who have another concomitant disease or malformation severely affecting the
             cardiovascular, pulmonary, CNS, liver or renal function that in the opinion of the
             Investigator may significantly affect likelihood to respond to treatment and/or
             assessment of emapalumab safety.

          -  History of hypersensitivity or allergy to any component of the study drug

          -  Receipt of a BCG vaccine within 12 weeks prior to screening.

          -  Receipt of live or attenuated live vaccines (other than BCG) within 6 weeks prior to
             screening.

          -  Pregnant or lactating female patients.