Clinical trial NCT03311854: 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)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Macrophage Activation Syndrome
Lymphohistiocytosis, Hemophagocytic
Arthritis, Juvenile
Adult Onset Still Disease
Keywords: Emapalumab
Gamifant
Macrophage activation syndrome
Secondary hemophagocytic lymphohistiocytosis
Interferon-gamma
Systemic juvenile idiopathic arthritis
Adult-onset Still's disease
MAS
HLH
sHLH
IFN-gamma
IFNγ
sJIA
AOSD
NI-0501-06
NI-0501
Lead sponsor: Swedish Orphan Biovitrum
Sponsor class: INDUSTRY
First posted: 2017-10-17
Enrollment: 14
Sex: ALL
Minimum age (years): 0
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 participants developing MAS, presenting an inadequate response to high dose glucocorticoid treatment.


Eligibility 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.
* An inadequate response to high dose i.v. glucocorticoid treatment administered for at least 3 days as per local standard of care (including but not limited to pulses of 30 mg/kg PDN on 3 consecutive days). High dose i.v. glucocorticoid should not be lower than 2 mg/kg/day of PDN equivalent in 2 divided doses (or at least 60 mg/day in patients of 30 kg or more). In case of rapid worsening of the patient's condition and/or lab parameters, inclusion may occur within less than 3 days from starting high dose i.v. glucocorticoids.
* 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.
* Pregnant or lactating female patients.

Primary outcomes:
measure: Incidence, Severity, Causality, and Outcomes of AEs (Serious and Nonserious)
timeFrame: Up to Week 8
measure: Evolution of Laboratory Parameters
timeFrame: Up to Week 8
measure: Number of Participants Withdrawn Due to Safety Reasons
timeFrame: Up to Week 8
measure: Number of Participants Achieving MAS Remission at Week 8 After Initiation of Emapalumab Treatment
timeFrame: Week 8
measure: Time to First MAS Remission
timeFrame: Up to Week 8
measure: Number of Participants for Whom Glucocorticoids Could be Permanently Tapered at Any Time During the Study
timeFrame: Up to Week 8
measure: Time to Achievement of Permanent Glucocorticoids Tapering
timeFrame: Up to Week 8
measure: Survival Time
timeFrame: Up to Week 8
measure: Number of Participants Withdrawn From the Study Due to Lack of Efficacy
timeFrame: Up to Week 8
measure: Levels of Emapalumab Concentration
timeFrame: Data from the following time points are presented: SD0 (pre- and post-dose), Week 4 Visit 2 (pre- and post-dose), and 4-week follow-up visit/EoS.
measure: Pharmacodynamic Parameters
timeFrame: Up to Week 8
measure: Number of Participants Who Demonstrated a Presence of Circulating Antibodies Against Emapalumab to Determine Immunogenicity
timeFrame: Up to Week 8
Secondary outcomes:
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: Cincinnati Children'S Hospital
state: Ohio
city: Paris
country: France
facility: Hôpital Necker-Enfants Malades, Unité d'Immunologie-hématologie et Rhumatologie pédiatriques
city: Rome
country: Italy
facility: IRCCS Ospedale Pediatrico, Bambino Gesù
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Deu
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children
Study officials:
References: