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

Hemophagocytic Lymphohistiocytoses Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03985423
• Other study ID #: NI-0501-10
• Status: Terminated
• Phase: Phase 2/Phase 3
• Start date: June 2, 2020
• Est. completion date: June 29, 2021

Study information

• Verified date: September 2023
• Source: Swedish Orphan Biovitrum
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: June 29, 2021
• Est. primary completion date: June 29, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hemophagocytic Lymphohistiocytoses
• Lymphohistiocytosis, Hemophagocytic

Intervention

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.

Locations

Country	Name	City	State
United States	MD Anderson Cancer Center	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Swedish Orphan Biovitrum	Light Chain Bioscience - Novimmune SA

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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