Clinical trial NCT03985423: A Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Emapalumab in Adult Patients With HLH
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Hemophagocytic Lymphohistiocytoses
Keywords: interferon gamma
emapalumab
adult HLH
malignancy-associated HLH
CXCL9
Lead sponsor: Swedish Orphan Biovitrum
Sponsor class: INDUSTRY
Collaborators: name: Light Chain Bioscience - Novimmune SA
First posted: 2019-06-13
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Overall Response
timeFrame: Week 4
Secondary outcomes:
measure: Best Response on Treatment
timeFrame: Week 4; End of Treatment Visit (on average of 12 weeks)
measure: Overall Response
timeFrame: End of Treatment Visit (on average of 12 weeks)
measure: Overall Survival
timeFrame: End of Treatment Visit (on average of 12 weeks)
measure: Time to Complete Response or Partial Response
timeFrame: Week 4; End of Treatment visit (on average of 12 weeks)
measure: Duration of Response
timeFrame: Up to 1 year after last emapalumab administration
measure: Hemophagocytic Lymphohistiocytosis Relapse
timeFrame: Up to 1 year after last emapalumab administration
measure: Incidence, Severity, Causality and Outcomes of Serious Adverse Events and Non-serious Adverse Events
timeFrame: Up to 1 year after last emapalumab administration
measure: Serum Concentrations of Emapalumab
timeFrame: Up to 1 year after last emapalumab administration
measure: Serum Biomarker Levels
timeFrame: Up to 1 year after last emapalumab administration
measure: Incidence of Anti-Drug Antibodies Against Emapalumab
timeFrame: Up to 1 year after last emapalumab administration
Other outcomes:
Locations:
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Swedish Orphan Biovitrum
name: Radmila Kanceva
role: STUDY_DIRECTOR
References: