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

Primary Purpose

Hemophagocytic Lymphohistiocytoses

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Emapalumab-Lzsg
Sponsored by
Swedish Orphan Biovitrum
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hemophagocytic Lymphohistiocytoses focused on measuring interferon gamma, emapalumab, adult HLH, malignancy-associated HLH, CXCL9

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • MD Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Emapalumab

Arm Description

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.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

Best Response on Treatment
As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description.
Overall Response
As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description.
Overall Survival
As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description.
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.
Duration of Response
As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description.
Hemophagocytic Lymphohistiocytosis Relapse
As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description.
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.
Serum Concentrations of Emapalumab
As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description.
Serum Biomarker Levels
Levels of interferon-gamma, C-X-C chemokine ligand 9, soluble CD25, interleukin-6.
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.

Full Information

First Posted
May 23, 2019
Last Updated
September 14, 2023
Sponsor
Swedish Orphan Biovitrum
Collaborators
Light Chain Bioscience - Novimmune SA
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1. Study Identification

Unique Protocol Identification Number
NCT03985423
Brief Title
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

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Terminated
Why Stopped
Sponsor Decision
Study Start Date
June 2, 2020 (Actual)
Primary Completion Date
June 29, 2021 (Actual)
Study Completion Date
June 29, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Swedish Orphan Biovitrum
Collaborators
Light Chain Bioscience - Novimmune SA

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemophagocytic Lymphohistiocytoses
Keywords
interferon gamma, emapalumab, adult HLH, malignancy-associated HLH, CXCL9

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
7 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Emapalumab
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Emapalumab-Lzsg
Other Intervention Name(s)
NI-0501
Intervention Description
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.
Primary Outcome Measure Information:
Title
Overall Response
Description
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).
Time Frame
Week 4
Secondary Outcome Measure Information:
Title
Best Response on Treatment
Description
As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description.
Time Frame
Week 4; End of Treatment Visit (on average of 12 weeks)
Title
Overall Response
Description
As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description.
Time Frame
End of Treatment Visit (on average of 12 weeks)
Title
Overall Survival
Description
As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description.
Time Frame
End of Treatment Visit (on average of 12 weeks)
Title
Time to Complete Response or Partial Response
Description
As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description.
Time Frame
Week 4; End of Treatment visit (on average of 12 weeks)
Title
Duration of Response
Description
As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description.
Time Frame
Up to 1 year after last emapalumab administration
Title
Hemophagocytic Lymphohistiocytosis Relapse
Description
As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description.
Time Frame
Up to 1 year after last emapalumab administration
Title
Incidence, Severity, Causality and Outcomes of Serious Adverse Events and Non-serious Adverse Events
Description
As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description.
Time Frame
Up to 1 year after last emapalumab administration
Title
Serum Concentrations of Emapalumab
Description
As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description.
Time Frame
Up to 1 year after last emapalumab administration
Title
Serum Biomarker Levels
Description
Levels of interferon-gamma, C-X-C chemokine ligand 9, soluble CD25, interleukin-6.
Time Frame
Up to 1 year after last emapalumab administration
Title
Incidence of Anti-Drug Antibodies Against Emapalumab
Description
As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description.
Time Frame
Up to 1 year after last emapalumab administration

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Radmila Kanceva
Organizational Affiliation
Swedish Orphan Biovitrum
Official's Role
Study Director
Facility Information:
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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

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