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)

Conditions: Macrophage Activation Syndrome; Lymphohistiocytosis, Hemophagocytic; Arthritis, Juvenile; Adult Onset Still Disease

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.

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