2024-516153-52-00已完成3 期
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 Arthitis and Adult Onset Still's Disease) or with MAS in Systemic Lupus Erythematosus
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 7
- 主要终点
- Proportion of patients with complete response (CR) at Week 8 after first administration of emapalumab.
研究概览
简要总结
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)
研究设计
- 研究类型
- Interventional
入排标准
- 年龄范围
- 0 years 至 65+ years（65+ Years, 18-64 Years, 0-17 Years）
- 接受健康志愿者
- 是
入选标准
- •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. (Run-in phase in all cohorts)
- •Cohort 2 (Specific inclusion criteria for Cohort 1 and Cohort 2): a. Confirmed diagnosis of SLE as per Systemic Lupus International Collaborating Clinics (SLICC) 2012 criteria.
- •Sexually active female patients of childbearing potential are expected to use highly effective methods of contraception during dosing and for 6 months after last dose of study drug. Highly effective contraception methods include: • Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation: o Oral. o Intravaginal. o Transdermal. • Progestogen-only hormonal contraception associated with inhibition of ovulation: o Oral. o Injectable. o Implantable. • Intra-uterine device. • Intra-uterine hormone-releasing system. • Bilateral tubal occlusion. • Vasectomised partner. • Sexual abstinence.
- •Male and female patients aged between 6 months and 80 years of age at the time of diagnosis of active MAS. (Run-in phase in all cohorts)
- •MAS defined as per the criteria defined below for each cohort and requiring treatment with GCs as per standard of care. (Run-in phase in all cohorts)
- •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. (Interventional phase in all cohorts)
- •Male and female patients aged between 6 months and 80 years of age at the time of diagnosis of active MAS. (Interventional phase in all cohorts)
- •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. (Interventional phase in all cohorts)
- •Diagnosis of active MAS confirmed by the treating rheumatologist, having ascertained the followings (Interventional phase in all cohorts): 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
- •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. (Interventional phase in all cohorts)
- •Cohort 1 (Specific inclusion criteria for Cohort 1 and Cohort 2): 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)
排除标准
- •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 pHLH or by the presence of family history.
- •Evidence of latent tuberculosis.
- •History of hypersensitivity or allergy to any component of the study drug.
- •Receipt of a Bacillus Calmette-Guerin (BCG) vaccine within 12 weeks prior to screening.
- •Receipt of a live or attenuated live (other than BCG) vaccine within 4 weeks prior to screening.
- •Pregnancy or lactating female patients.
- •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.
- •Treatment with canakinumab, Janus kinase (JAK) inhibitors, Tumour necorsis factor (TNF) inhibitors and tocilizumab at the time of emapalumab initiation.
- •Ongoing treatment with anakinra at a dose above 4 mg/kg/ day at time of emapalumab initiation.
- •Patients treated with etoposide for MAS in the last 1 month.
- •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.
- •Foreseeable inability to cooperate with given instructions or study procedures.
- •Clinically active mycobacteria (typical and atypical), Histoplasma Capsulatum, or Salmonella infections.
- •Evidence of leishmania infections.
结局指标
主要结局
Proportion of patients with complete response (CR) at Week 8 after first administration of emapalumab.
Proportion of patients with complete response (CR) at Week 8 after first administration of emapalumab.
次要结局
- 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.
研究者
Swedish Orphan Biovitrum AG (Sobi AG), Clinical Development Swedish Orphan
Scientific
Swedish Orphan Biovitrum AG
研究点 (7)
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