macrophage activation syndrome MAS
Conditions
Interventions
Patients enrolled in the Interventional phase will receive emapalumab.
Emapalumab will be administered by i.v. infusion at an initial dose of 6 mg/kg
over a period of 1 to 2 hours depending on the v
Sponsors
Swedish Orphan International
Eligibility
Age
No minimum to 99 Years
Inclusion criteria
Inclusion criteria: Inclusion criteria Run-in phase in all cohorts 1. Informed consent provided by the patient or by the patient's legally authorized representative(s) with the assent of patients who are legally capable of providing it, as required by local law. 2. Male and female patients aged between 6 months and 80 years of age at the time of diagnosis of active MAS. 3. MAS defined as per the criteria defined below for each cohort and requiring treatment with GCs as per standard of care. Interventional phase in all cohorts 1. Informed consent provided by the patient or by the patient's legally authorized representative(s) with the assent of patients who are legally capable of providing it, as required by local law. 2. Male and female patients aged between 6 months and 80 years of age at the time of diagnosis of active MAS. 3. Patients who have shown an inadequate response to high dose intravenous (i.v.) GCs administered for at least 3 days according to local standard clinical practice, including but not limited to pulses of 30 mg/kg methylprednisolone (mPDN) on 3 consecutive days. High i.v. GCs dose is recommended not to be lower than 2 mg/kg/ day PDN equivalent (or at least 60 mg/day in pediatric patients of 30 kg or more and at least 1 g/day in adult MAS patients). In case of rapid worsening of the patient*s condition and/or laboratory parameters, as per Investigator judgment, inclusion may occur within less than 3 days from starting high dose GCs. 4. Diagnosis of active MAS confirmed by the treating rheumatologist, having ascertained the followings: a. Febrile patients presenting with ferritin > 684 ng/mL. b. and any 2 of: i. Platelet count 48 U/L iii. Triglycerides > 156 mg/dL iv. Fibrinogen level
Exclusion criteria
Exclusion criteria: 1. Primary hemophagocytic lymphohistiocytosis (pHLH) documented by either the presence of a known causative genetic mutation or abnormal perforin expression or CD107a degranulation assay as described with pHLH or by the presence of family history. 2. Confirmed malignancy. Note: patients with a suspected malignancy should have mononuclear cells typed by flow cytometry and/or tissue biopsy, as applicable, to rule out malignancy. 3. Treatment with canakinumab, Janus kinase (JAK) inhibitors, tumor necrosis factor (TNF) inhibitors and tocilizumab at the time of emapalumab initiation. 4. Ongoing treatment with anakinra at a dose above 4 mg/kg/day at time of emapalumab initiation. 5. Patients treated with etoposide for MAS in the last 1 month. 6. Presence of any medical or psychological condition or laboratory result that in the opinion of the Investigator can interfere with the patient's ability to comply with the protocol requirements or makes the patient not appropriate for inclusion to the study and treatment with emapalumab. 7. Foreseeable inability to cooperate with given instructions or study procedures. 8. Clinically active mycobacteria (typical and atypical), Histoplasma Capsulatum, or Salmonella infections. 9. Evidence of leishmania infections. 10. Evidence of latent TB. 11. History of hypersensitivity or allergy to any component of the study drug. 12. Receipt of a Bacillus Calmette-Guerin (BCG) vaccine within 12 weeks prior to Screening. 13. Receipt of a live or attenuated live (other than BCG) vaccine within 4 weeks prior to Screening. 14. Pregnancy or lactating female patients.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary efficacy endpoint: • Proportion of patients with complete response (CR) at Week 8 after first administration of emapalumab. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary endpoints: • GCs tapering to a dose | — |
Countries
Netherlands
Outcome results
None listed