A Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Emapalumab in Adult Patients With HLH

A Phase 2/3, Open-label, Single Arm, Multicenter Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Emapalumab in Adult Patients With Hemophagocytic Lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening condition characterized by uncontrolled hyperinflammation which may develop on the background of several clinical conditions (e.g. autoimmune disease, infection, malignancy). Emapalumab (previously referred to as NI-0501) is a monoclonal antibody neutralizing interferon-gamma (IFN-gamma), a key cytokine driving the inflammation and tissue damage seen in HLH. The purpose of this study is to assess the efficacy, safety and pharmacokinetics of emapalumab in adult patients with secondary HLH.

Study NI-0501-10 is an open-label, single arm, multicenter, Phase 2/3 interventional study.

The study enrolls adult patients with hemophagocytic lymphohistiocytosis (HLH), specifically newly diagnosed patients with malignancy-associated HLH (M-HLH), and newly diagnosed or previously treated patients with non-malignancy-associated HLH.

Inclusion Criteria:

• Male and female patients of age 18 and older at the time of HLH diagnosis
• Fulfilment of 5 of the 8 HLH-2004 clinical criteria
• Patients diagnosed with malignancy-associated 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 or idiopathic HLH who have already received conventional therapy for HLH must have failed prior treatment as per the treating physician's judgement
• 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
• Current 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 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
• History of hypersensitivity or allergy to any components of emapalumab
• Active mycobacteria, Histoplasma capsulatum, or Leishmania infections
• Evidence of latent tuberculosis
• 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