A study to evaluate efficacy, safety and tolerability, pharmacokinetics and pharmacodynamics of emapalumab in children and adults with macrophage activation syndrome (MAS)

• Register: EUCTR
• Last refreshed on: 3 February 2025
• Main ID: EUCTR2021-001577-24-NL
• Date of registration: 21/04/2022
• Prospective Registration: Yes
• Primary sponsor: Swedish Orphan Biovitrum AG (Sobi AG)
• Public title: A study to evaluate efficacy, safety and tolerability, pharmacokinetics and pharmacodynamics of emapalumab in children and adults with macrophage activation syndrome (MAS)
• Scientific title: 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 Still’s disease (Including Systemic Juvenile Idiopathic Arthritis and Adult onset Still’s disease) or with MAS in Systemic Lupus Erythematous - NI-0501-14
• Date of first enrolment: 31/08/2022
• Target sample size: 41
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2021-001577-24
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: Placebo: Other: Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Canada, China, Czech Republic, Czechia, France, Germany, Italy, Japan, Netherlands, Poland, Russian Federation, Spain, Sweden, United Kingdom, United States

Contacts

• Name: Clinical Development Swedish Orphan
• Affiliation: Swedish Orphan Biovitrum AG (Sobi AG)

• Name: Clinical Development Swedish Orphan
• Affiliation: Swedish Orphan Biovitrum AG (Sobi AG)

Key inclusion & exclusion 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 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.
Are the trial subjects under 18? yes
Number of subjects for this age range: 22
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 15
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 4

Exclusion criteria:
1. Primary hemophagocytic lymphohistiocytosis (p-HLH) documented by either the presence of a known causative genetic mutation or abnormal perforin expression or CD107a degranulation assay as described with p-HLH 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, Tumour necorsis 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 tuberculosis.
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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Macrophage activation syndrome (MAS) in the context of Systemic Juvenile Idiopathic Arthritis (sJIA) and Adult onset Still’s disease (AOSD). MAS in the context of pediatric and adult Systemic Lupus Erythematous (SLE).
MedDRA version: 21.1 Level: PT Classification code 10071583 Term: Haemophagocytic lymphohistiocytosis System Organ Class: 10021428 - Immune system disorders

Intervention(s)

Product Name: Emapalumab
Product Code: NI-0501
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Emapalumab
Current Sponsor code: NI-0501
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-

Product Name: Emapalumab
Product Code: NI-0501
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Emapalumab
Current Sponsor code: NI-0501
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-

Primary Outcome(s)

Secondary Objective: ? To demonstrate efficacy of emapalumab with respect to tapering of glucocorticoids (GCs).
? To evaluate the time to onset of response to emapalumab treatment.
? To evaluate efficacy of emapalumab with respect to overall response (OR).
? To evaluate the sustained efficacy of emapalumab treatment.
? To evaluate the patient's survival after treatment with emapalumab.
? To evaluate the safety and tolerability of emapalumab.
? To evaluate patient-reported outcome of MAS in patients treated with emapalumab.
? To determine the pharmacokinetic (PK) profile of emapalumab.
? To determine the pharmacodynamic (PD) profile of emapalumab.
? To determine the immunogenicity of emapalumab

Main Objective: To demonstrate efficacy of emapalumab in the treatment of patients in:
- Cohort 1: Macrophage Activation Syndrome (MAS) in the context of systemic juvenile idiopathic arthritis and adult onset Still’s disease (AOSD).
- Cohort 2: MAS in the context of pediatric and adult systemic lupus erythematosus (SLE).

Timepoint(s) of evaluation of this end point: week 8

Primary end point(s): Proportion of patients with complete response (CR) at Week 8 after first administration of emapalumab.

Secondary Outcome(s)

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

Timepoint(s) of evaluation of this end point: duration of study

Secondary ID(s)

NI-0501-14

2021-001577-24-ES

Source(s) of Monetary Support

Swedish Orphan Biovitrum AG (Sobi AG)

Ethics review

Status: Approved
Approval date: 31/08/2022
Contact: