A Study to Investigate the Safety and Efficacy of an Anti-IFN-gamma mAb in Children With Systemic Juvenile Idiopathic Arthritis (sJIA) Developing Macrophage Activation Syndrome/ Secondary Hemophagocytic Lymphohistiocytosis (MAS/sHLH)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03311854
Recruitment Status : Recruiting
First Posted : October 17, 2017
Last Update Posted : March 26, 2018
Information provided by (Responsible Party):
NovImmune SA

Brief Summary:
Macrophage Activation Syndrome (MAS) is a rare, life-threatening condition characterized by uncontrolled hyperinflammation which may develop on the background of systemic Juvenile Idiopathic Arthritis (sJIA). NI-0501 (Emapalumab) is a monoclonal antibody neutralizing interferon-gamma (IFN-gamma), a key cytokine which contributes to the inflammation and tissue damage seen in MAS. The purpose of this study is to assess the safety, tolerability and efficacy of NI-0501 in sJIA patients developing MAS, presenting an inadequate response to high dose glucocorticoid treatment.

Condition or disease Intervention/treatment Phase
Macrophage Activation Syndrome Lymphohistiocytosis, Hemophagocytic Arthritis, Juvenile Drug: NI-0501 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot, Open-label, Single Arm, Multicenter Study to Evaluate Safety, Tolerability, Pharmacokinetics and Efficacy of Intravenous Administrations of NI-0501, an Anti-interferon Gamma (Anti-IFNγ) Monoclonal Antibody, in Patients With Systemic Juvenile Idiopathic Arthritis (sJIA) Developing Macrophage Activation Syndrome/Secondary HLH (MAS/sHLH)
Actual Study Start Date : March 2, 2018
Estimated Primary Completion Date : May 2021
Estimated Study Completion Date : May 2021

Arm Intervention/treatment
Experimental: NI-0501 Drug: NI-0501
NI-0501 will be administered at the initial dose of 6 mg/kg by intravenous infusion. NI-0501 treatment will be continued at the dose of 3 mg/kg, every 3 days until study day 15, and then twice-a-week for an additional 2 weeks, i.e. until study day 28.

Primary Outcome Measures :
  1. Incidence, severity, causality and outcomes of AEs (serious and nonserious). [ Time Frame: Up to Week 8 ]
  2. Levels of NI-0501. [ Time Frame: Up to week 8 ]
  3. Serum biomarker levels. [ Time Frame: Up to Week 8 ]
    Levels of INF-gamma, CXCL9 and CXCL10

  4. Levels (if any) of circulating antibodies against NI-0501 to determine immunogenicity. [ Time Frame: Up to Week 8 ]

Secondary Outcome Measures :
  1. Number of patients achieving MAS remission by Week 8 after initiation of NI-0501 treatment. [ Time Frame: Week 8 ]
  2. Time to MAS remission. [ Time Frame: Up to Week 8 ]
  3. Number of patients for whom glucocorticoids can be tapered. [ Time Frame: Up to Week 8 ]
  4. Time to glucocorticoids tapering. [ Time Frame: Up to Week 8 ]
  5. Overall survival [ Time Frame: Up to Week 8 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients of both genders, aged <18 years.
  • Confirmed sJIA or high presumption of sJIA.
  • Diagnosis of active MAS.
  • Patient presenting an inadequate response to high dose i.v. glucocorticoid treatment.
  • Informed consent provided by the patient (as required by local law), or by the patient's legally authorized representative(s) with the assent of patients who are legally capable of providing it, as applicable.

Exclusion Criteria:

  • Diagnosis of suspected or confirmed primary HLH or HLH consequent to a neoplastic disease.
  • Patients treated with Tocilizumab, Canakinumab or TNF inhibitors within 5 times of their defined half-life.
  • Active mycobacteria (typical and atypical), Histoplasma Capsulatum, Shigella, Salmonella, Campylobacter and Leishmania infections.
  • Clinical suspicion of latent tuberculosis.
  • Positive serology for HIV antibodies.
  • Presence of malignancy.
  • Receipt of a BCG vaccine within 12 weeks prior to screening.
  • Receipt of live or attenuated live vaccines (other than BCG) within 6 weeks prior to screening.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03311854

Contact: Maria Ballabio, MD +41 61 201 1324

Ospedale Pediatrico Bambino Gesù - UO Reumatologia Recruiting
Rome, Italy, 00165
Contact: Fabrizio de Benedetti, MD    00390668592309 ext 2659   
Principal Investigator: Fabrizio de Benedetti, MD         
Sponsors and Collaborators
NovImmune SA

Responsible Party: NovImmune SA Identifier: NCT03311854     History of Changes
Other Study ID Numbers: NI-0501-06
First Posted: October 17, 2017    Key Record Dates
Last Update Posted: March 26, 2018
Last Verified: March 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Arthritis, Juvenile
Lymphohistiocytosis, Hemophagocytic
Macrophage Activation Syndrome
Pathologic Processes
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Histiocytosis, Non-Langerhans-Cell
Lymphatic Diseases
Lymphoproliferative Disorders
Immunoproliferative Disorders