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 Overview

• Status: Terminated
• Conditions: Hemophagocytic Lymphohistiocytoses
• Intervention / Treatment: Drug: Emapalumab-Lzsg

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.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Emapalumab; Patients were administered Emapalumab-Lzsg by intravenous (i.v.) infusion over a period of 1 to 2 hours, at an initial dose of 6 mg/kg and continued at 3 mg/kg, every 3 days for the first 2 weeks (Study Day [SD] 15), and then twice-a-week. If the treating physician deemed appropriate, the dose of emapalumab could be increased (up to 10 mg/kg), guided by clinical and laboratory response.

Drug: Emapalumab-Lzsg; Patients were administered Emapalumab-Lzsg by intravenous (i.v.) infusion over a period of 1 to 2 hours, at an initial dose of 6 mg/kg and continued at 3 mg/kg, every 3 days for the first 2 weeks (Study Day [SD] 15), and then twice-a-week. If the treating physician deemed appropriate, the dose of emapalumab could be increased (up to 10 mg/kg), guided by clinical and laboratory response.; Other Names: NI-0501

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response	Achievement of either a Complete or Partial Response Complete Response is adjudicated if the following are observed: No fever = body temperature <37.5°C; Normal spleen size; No cytopenia = Absolute Neutrophil Counts >=1.0x10^9/L and platelet count >=100x10^9/L [absence of G-CSF and transfusion support must be documented for at least 4 days to report no cytopenia]; No hyperferritinemia = serum level is <2000 µg/L; No evidence of coagulopathy, i.e., normal D-Dimer and/or normal (>150 mg/dL) fibrinogen levels; No neurological and CSF abnormalities attributed to HLH; No sustained worsening of sCD25 (as indicated by at least two consecutive measurements that are >2-fold higher than baseline) Partial Response is adjudicated if there is an improvement (>50% change from baseline or normalization) of at least 3 HLH clinical and laboratory criteria (including Central Nervous System abnormalities).	Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best Response on Treatment	As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description.	Week 4; End of Treatment Visit (on average of 12 weeks)
Overall Response	As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description.	End of Treatment Visit (on average of 12 weeks)
Overall Survival	As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description.	End of Treatment Visit (on average of 12 weeks)
Time to Complete Response or Partial Response	As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description.	Week 4; End of Treatment visit (on average of 12 weeks)
Duration of Response	As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description.	Up to 1 year after last emapalumab administration
Hemophagocytic Lymphohistiocytosis Relapse	As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description.	Up to 1 year after last emapalumab administration
Incidence, Severity, Causality and Outcomes of Serious Adverse Events and Non-serious Adverse Events	As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description.	Up to 1 year after last emapalumab administration
Serum Concentrations of Emapalumab	As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description.	Up to 1 year after last emapalumab administration
Serum Biomarker Levels	Levels of interferon-gamma, C-X-C chemokine ligand 9, soluble CD25, interleukin-6.	Up to 1 year after last emapalumab administration
Incidence of Anti-Drug Antibodies Against Emapalumab	As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description.	Up to 1 year after last emapalumab administration

Collaborators and Investigators

• Sponsor: Swedish Orphan Biovitrum
• Collaborators: Light Chain Bioscience - Novimmune SA
• Investigators: Study Director: Radmila Kanceva, Swedish Orphan Biovitrum

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2020
• Primary Completion (Actual): June 29, 2021
• Study Completion (Actual): June 29, 2021

Study Registration Dates

• First Submitted: May 23, 2019
• First Submitted That Met QC Criteria: June 12, 2019
• First Posted (Actual): June 13, 2019

Study Record Updates

• Last Update Posted (Actual): October 6, 2023
• Last Update Submitted That Met QC Criteria: September 14, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: emapalumab; interferon gamma; adult HLH; malignancy-associated HLH; CXCL9
• Additional Relevant MeSH Terms: Lymphatic Diseases; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphohistiocytosis, Hemophagocytic
• Other Study ID Numbers: NI-0501-10

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No