A two-cohort, open-label, single arm, multicenter study to evaluate efficacy, safety and tolerability, pharmacokinetics and pharmacodynamics, of emapalumab in children and adults with macrophage activation syndrome (MAS) in Stills disease (including systemic juvenile idiopathic arthritis and Adult onset Stills disease) or with MAS in Systemic lupus erythematous

Phase 2

Recruiting

Conditions: MAS
10003816
macrophage activation syndrome

Registration Number: NL-OMON52297

Lead Sponsor: Swedish Orphan International

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 5

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 <= 181 x109/L
ii. Aspartate aminotransferase (AST) -level > 48 U/L
iii. Triglycerides > 156 mg/dL
iv. Fibrinogen level <= 360 mg/dL
5. Female patients of child-bearing potential (sexually or non sexually
active). Female patients who are sexually active must be willing to use highly
effective methods of contraception from study drug initiation to 6 months after
the last dose of study drug.
Specific inclusion criteria for Cohort 1 and Cohort 2
6. Cohort 1:
a. Confirmed sJIA diagnosis. For patients presenting with MAS in the context of
the onset of sJIA, high presumption of sJIA will suffice for eligibility.
b. Confirmed diagnosis of AOSD as per Yamaguchi criteria (Yamaguchi et al.
1992).
7. Cohort 2:
a. Confirmed diagnosis of SLE as per Systemic Lupus International Collaborating
Clinics (SLICC) 2012-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.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary efficacy endpoint:<br /><br>• Proportion of patients with complete response (CR) at Week 8 after first<br /><br>administration of emapalumab.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary endpoints:<br /><br>• GCs tapering to a dose < 50 % of prednisolone (PDN) equivalent at the time of<br /><br>emapalumab start or to the same (or lower) dose being administered before the<br /><br>occurrence of MAS (in patients already treated for the underlying condition)<br /><br>whichever occurs first at any time during the study.<br /><br>• GCs tapering to <=1mg/kg/day of PDN equivalent at any time during the study.<br /><br>• Time to achieve GCs tapering (as defined in the 2 bullets above).<br /><br>• Time to first CR.<br /><br>• Proportion of patients with OR as defined by CR or partial response (PR).<br /><br>• Time to first OR as defined by CR or PR.<br /><br>• MAS recurrence at any time after achievement of CR<br /><br>• Withdrawal from the study due to lack of response as per Investigator<br /><br>decision.<br /><br>• Survival time.</p><br>