Evaluate Efficacy, Safety and Tolerability, PK and PD of Emapalumab in Children and Adults With MAS in Still's or SLE

JRCT ID: jRCT2031220187

Registered date:07/07/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Macrophage Activation Syndrome, Secondary Hemophagocytic Lymphohistiocytosis, Still Disease, SLE
• Date of first enrollment: 01/03/2023
• Target sample size: 2
• Countries of recruitment: Belgium,Japan,Canada,Japan,China,Japan,Czechia,Japan,France,Japan,Germany,Japan,Italy,Japan,Netherlands,Japan,Poland,Japan,Spain,Japan,Sweden,Japan,United Kingdom,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

Emapalumab iv infusion
initial dose: 6 mg/kg
Subsequent doses: 3 mg/kg

Outcome(s)

• Primary Outcome: Proportion of subjects with complete response (CR) at Week 8 after first administration of emapalumab

Secondary Outcome

- GCs tapering to a dose below 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 whichever occurs first
- GCs tapering to <=1mg/kg/day of PDN equivalent at any time during the study.
- Time to achieve GCs tapering as defined above.
- Time to first Complete Remission (CR)
- Proportion of subjects with overall response (OR) as defined by CR or Partial Remission (PR)
- Time to first OR as defined by CR or PR
- MAS recurrence at anytime after achievement of CR
- Withdrawal from the study due to lack of response as per Investigator decision
- Survival time

Key inclusion & exclusion criteria

• Age minimum: >= 6month old
• Age maximum: <= 80age old
• Gender: Both

Include 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 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 mPDN on 3 consecutive days. High i.v. GCs dose is recommended not 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 following:
a. Febrile patients presenting with ferritin > 684 ng/mL
b. and any 2 of:
i. Platelet count <= 181 x10^9/L
ii. AST-level > 48 U/L
iii. Triglycerides > 156 mg/dL
iv. Fibrinogen level <= 360 mg/dL
5. Female patients of childbearing potential (sexually or nonsexually 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
1. 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.
2. Cohort 2:
a. Confirmed diagnosis of SLE as per SLICC 2012 criteria.

Exclude 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, JAK inhibitors, 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 infection.
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.

Related Information

• Primary Sponsor: Ochiai Kazuya
• Secondary ID(s): NCT05001737,2021-001577-24