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A Study to Investigate the Safety and Efficacy of Emapalumab, an Anti-IFN-gamma mAb in Patients With Systemic Juvenile Idiopathic Arthritis (sJIA) or Adult-onset Still's Disease (AOSD) Developing Macrophage Activation Syndrome/Secondary HLH (MAS/sHLH)

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ClinicalTrials.gov Identifier: NCT03311854
Recruitment Status : Completed
First Posted : October 17, 2017
Last Update Posted : June 24, 2021
Sponsor:
Information provided by (Responsible Party):
Swedish Orphan Biovitrum

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) or Adult-onset Still's Disease (AOSD). 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 emapalumab in sJIA or AOSD 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 Adult Onset Still Disease Drug: Emapalumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 14 participants
Allocation: N/A
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 Emapalumab, an Anti-interferon Gamma (Anti-IFNγ) Monoclonal Antibody, in Patients With Systemic Juvenile Idiopathic Arthritis (sJIA) or Adult-onset Still's Disease (AOSD) Developing Macrophage Activation Syndrome/Secondary HLH (MAS/sHLH)
Actual Study Start Date : March 2, 2018
Actual Primary Completion Date : May 19, 2020
Actual Study Completion Date : May 19, 2020


Arm Intervention/treatment
Experimental: Emapalumab Drug: Emapalumab
Emapalumab will be administered at the initial dose of 6 mg/kg by intravenous infusion. Emapalumab 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.
Other Name: Gamifant




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

  4. Levels (if any) of circulating antibodies against emapalumab to determine immunogenicity. [ Time Frame: Up to Week 8 ]
  5. Number of patients achieving MAS remission by Week 8 after initiation of emapalumab treatment. [ Time Frame: Week 8 ]
  6. Time to MAS remission. [ Time Frame: Up to Week 8 ]
  7. Number of patients for whom glucocorticoids can be tapered and time to achievement of glucocorticoids tapering. [ Time Frame: Up to Week 8 ]
  8. Overall survival [ Time Frame: Up to Week 8 ]
  9. Number of patients withdrawn from the study due to lack of efficacy. [ Time Frame: Up to Week 8 ]


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

Inclusion Criteria:

  • Patients of both genders
  • For sJIA patients: Confirmed sJIA diagnosis. For patients presenting with MAS in the context of the onset of sJIA, high presumption of sJIA will suffice for eligibility.For AOSD patients: confirmed AOSD diagnosis as per Yamaguchi criteria.
  • Diagnosis of active MAS.
  • Patient presenting an inadequate response to high dose i.v. glucocorticoid treatment.
  • Tocilizumab, TNF inhibitors and canakinumab, if administered, have to be discontinued before emapalumab initiation.
  • Having received guidance on contraception for both male and female patients sexually active and having reached puberty. Females of child-bearing potential require use of highly effective contraceptive measures.Males with partners(s) of child-bearing potential must agree to take appropriate precautions.
  • 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.
  • 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.
  • Patients who have another concomitant disease or malformation severely affecting the cardiovascular, pulmonary, CNS, liver or renal function that in the opinion of the Investigator may significantly affect likelihood to respond to treatment and/or assessment of emapalumab safety.
  • History of hypersensitivity or allergy to any component of the study drug
  • 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 ClinicalTrials.gov identifier (NCT number): NCT03311854


Locations
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United States, Ohio
Cincinnati Children'S Hospital
Cincinnati, Ohio, United States, 45229
France
Hôpital Necker-Enfants Malades, Unité d'Immunologie-hématologie et Rhumatologie pédiatriques
Paris, France, 75743
Italy
Ospedale Pediatrico Bambino Gesù - UO Reumatologia
Rome, Italy, 00165
Spain
Hospital Sant Joan de Deu
Esplugues De Llobregat, Spain, 08950
United Kingdom
Great Ormond Street Hospital
London, United Kingdom, WC1N 3JH
Sponsors and Collaborators
Swedish Orphan Biovitrum
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Responsible Party: Swedish Orphan Biovitrum
ClinicalTrials.gov Identifier: NCT03311854    
Other Study ID Numbers: NI-0501-06
First Posted: October 17, 2017    Key Record Dates
Last Update Posted: June 24, 2021
Last Verified: June 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Arthritis
Arthritis, Juvenile
Still's Disease, Adult-Onset
Lymphohistiocytosis, Hemophagocytic
Macrophage Activation Syndrome
Syndrome
Disease
Pathologic Processes
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Arthritis, Rheumatoid
Lymphoproliferative Disorders
Immunoproliferative Disorders
Histiocytosis, Non-Langerhans-Cell
Histiocytosis
Lymphatic Diseases