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

NCT03985423 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: NI-0501-10
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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.

Conditions

Hemophagocytic Lymphohistiocytoses

Keywords

interferon gamma; emapalumab; adult HLH; malignancy-associated HLH; CXCL9

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• Best Response on Treatment

  Week 4; End of Treatment Visit (on average of 12 weeks)

• Overall Response

  End of Treatment Visit (on average of 12 weeks)

• Overall Survival

  End of Treatment Visit (on average of 12 weeks)

• Time to Complete Response or Partial Response

  Week 4; End of Treatment visit (on average of 12 weeks)

• Duration of Response

  Up to 1 year after last emapalumab administration

Study Arms (1)

Emapalumab

EXPERIMENTAL

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

Interventions

Emapalumab-Lzsg DRUG

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.

Also known as: NI-0501

Emapalumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Swedish Orphan Biovitrum: lead
• Light Chain Bioscience - Novimmune SA: collaborator

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Lymphohistiocytosis, Hemophagocytic

Interventions

Emapalumab

Condition Hierarchy (Ancestors)

Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases

Limitations and Caveats

Since the study was prematurely terminated, and considering the low number of patients enrolled, no analysis related to primary and secondary efficacy endpoints and no Pharmacokinetic and Pharmacodynamic summary statistics were performed. Accordingly, no conclusion on the efficacy of emapalumab on this patient population could be withdrawn from the study.

Results Point of Contact

• Title: Radmila Kanceva, MD
• Organization: Sobi

radmila.kanceva@sobi.com

+4686972000

Study Officials

• Radmila Kanceva

  Swedish Orphan Biovitrum

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2019
• First Posted: June 13, 2019
• Study Start: June 2, 2020
• Primary Completion: June 29, 2021
• Study Completion: June 29, 2021
• Last Updated: October 6, 2023
• Results First Posted: October 6, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)