Clinical Trials

Inclusion Criteria:

• Male and female patients, aged 18 and older at the time of HLH diagnosis.
• Fulfilment of HLH-2004 clinical criteria; i.e., five of the eight criteria below:
  • Fever;
  • Splenomegaly;
  • Cytopenias affecting 2 of 3 lineages in the peripheral blood (hemoglobin <90 g/L; platelets < 100 x 10^9/L; neutrophils <1 x 10^9/L);
• • Hypertriglyceridemia  (fasting  triglycerides  ≥ 3  mmol/L  or ≥ 265 mg/dL)  and/or  hypofibrinogenemia  (fibrinogen ≤1.5 g/L);
• • Hemophagocytosis in bone marrow, spleen or lymph nodes;
  • Low or absent natural killer (NK)cell activity;
  • Ferritin ≥ 500 µg/L;
  • Soluble CD25 (sCD25; i.e., soluble IL2 receptor) ≥ 2400 U/mL (or equivalent, in case the local lab uses different units).
• Patients diagnosed with M-HLH must be treatment naïve; patients diagnosed with HLH driven by any other etiology or idiopathic can be either treatment naïve or treatment experienced.
• Patients with non-malignancy-associated HLH who have already received conventional therapy for HLH must have failed prior treatment as per the treating physician`s judgement. At the time of enrolment, eligible treatment experienced patients may or may not be receiving conventional therapy.
• JAK inhibitors, if administered, must be discontinued before emapalumab initiation.
• Informed consent signed by the patient or by the patient’s legally authorized representative(s) (as required by local law).
• Willing to use highly effective methods of contraception from study drug initiation to 6 months after the last dose of study drug, if female and of childbearing potential.

Exclusion Criteria:

• Primary HLH (documented by the presence of known causative genetic mutations or by the presence of family history).
• Current (within 60 days from SD0) or scheduled administration of therapies known to trigger the cytokine release syndrome (e.g., chimeric antigen receptor (CAR)-modified T cells, bispecific T cell- engaging antibodies).
• Current (within 60 days from SD0) or scheduled administration of PD-1/PD-L1/CTLA-4 inhibitors.
• Life-expectancy associated with the underlying disease (triggering HLH) < 3 months.
• Ongoing participation in an investigational trial, or administration of any investigational treatment within 30 days from Screening.
• History of hypersensitivity or allergy to any components of emapalumab.
• Active mycobacteria, Histoplasma capsulatum, or Leishmania infections.
• Evidence of latent tuberculosis.
• Infection with HIV (HIV ELISA or PCR positive), hepatitis B (HBsAg positive), Hepatitis C (anti-HCV positive) unless the viral load by PCR is negative.
• Concomitant diseases that in the opinion of the Investigator may significantly affect the likelihood of a response to treatment and/or the assessment of emapalumab safety and/or efficacy.
• Receipt of a bacille Calmette-Guerin (BCG) vaccine within 12 weeks prior to Screening.
• Receipt of a live or attenuated live (other than BCG) vaccine within 6 weeks prior to Screening.
• Pregnancy or lactation (female patients).