An Open-Label Uncontrolled Multicenter Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety and Activity of Nipocalimab in Children Aged 2 to Less Than 18 Years With Generalized Myasthenia Gravis
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 12
- 试验地点
- 31
- 主要终点
- Change from Baseline in Total Serum Immunoglobulin-G (IgG) Levels
研究概览
简要总结
The purpose of this study is to determine the effect of nipocalimab on total serum immunoglobulin G (IgG) in pediatric participants 2 to less than (<) 18 years of age (globally) and 8 to <18 years of age (for Unites Stated (US) sites only), the safety and tolerability of treatment with nipocalimab in children and adolescents and to evaluate the pharmacokinetics (PK) of nipocalimab in children and adolescents with generalized myasthenia gravis (gMG) who have an insufficient clinical response to ongoing, stable standard-of-care therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age: For US sites only: 8 to < 18 years
- •Diagnosis of myasthenia gravis (MG) with generalized muscle weakness meeting the clinical criteria for generalized myasthenia gravis (gMG) as defined by the Myasthenia Gravis Foundation of America (MGFA) Clinical Classification Class IIa/b, IIIa/b, or IVa/b at screening
- •Has a positive serologic test for acetylcholine receptor (anti-AChR) antibodies or muscle-specific tyrosine kinase (anti-MuSK) antibodies at screening
- •A participant using herbal, naturopathic, traditional Chinese remedies, ayurvedic or nutritional supplements, or medical marijuana (with a doctor's prescription) is eligible if the use of these medications is acceptable to the Investigator. These remedies must remain at a stable dose and regimen throughout the study
- •Has sufficient venous access to allow drug administration by infusion and blood sampling as per the protocol
- •Participants should have a body weight and body mass index between 5th and 95th percentile for age and sex. Obese participants greater than 95th percentile and underweight participants below 5th percentile may participate following medical clearance
- •A female of childbearing potential must have a negative highly sensitive serum (beta-human chorionic gonadotropin [beta-hCG]) at Screening and a negative urine pregnancy test at Day 1 prior to administration of study intervention
排除标准
- •Has a history of severe and/or uncontrolled hepatic (example, viral/alcoholic/ autoimmune hepatitis/ cirrhosis/ and/or metabolic liver disease), gastrointestinal, renal, pulmonary, cardiovascular (including congenital heart diseases), psychiatric, neurological musculoskeletal disorder, any other medical disorder(s) (example, diabetes mellitus), risk factors for thrombosis events (example, a history of venous thromboembolism [VTE] or antiphospholipid syndrome, or a personal or family history of heritable coagulation disorder such as factor V leiden, protein S or protein C deficiency, atrial fibrillation/flutter, major orthopedic surgery or significant trauma that may increase the risk of VTE, is expected to be immobilized for prolonged periods of time), or has clinically significant abnormalities in screening laboratory, that might interfere with participant's full participation in the study, and/ or might jeopardize the safety of the participant or the validity of the study results
- •Has any confirmed or suspected clinical immunodeficiency syndrome not related to treatment of his/her generalized myasthenia gravis (gMG), or has a family history of congenital or hereditary immunodeficiency unless confirmed absent in the participant
- •Has had a thymectomy within 12 months prior to screening, or thymectomy is planned during the Active treatment Phase of the study
- •Has shown a previous severe immediate hypersensitivity reaction, such as anaphylaxis to therapeutic proteins (example, monoclonal antibodies)
- •Has experienced myocardial infarction, unstable ischemic heart disease, or stroke within 12 weeks of screening
研究组 & 干预措施
Nipocalimab
Participants age 2 to less than (<) 18 years of age (globally) and 8 to <18 years of age (for US sites only) will be divided into 2 cohorts as per their age-adolescents 12 to <18 years and children 2 to <12 years and will receive nipocalimab once every two weeks for 24 weeks. After Week 24, all participants will have the option to enroll in long term extension (LTE).
干预措施: Nipocalimab (Drug)
结局指标
主要结局
Change from Baseline in Total Serum Immunoglobulin-G (IgG) Levels
时间窗: Up to 3 years
Change from baseline in total serum IgG levels were reported.
Number of Participants with Infectious Adverse Events (AEs)
时间窗: Up to 3 years
Number of participants with infectious AEs will be reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.
Number of Participants with Serious AEs (SAEs)
时间窗: Up to 3 years
Number of participants with SAEs will be reported. A SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect, is suspected transmission of any infectious agent via a medicinal product, is medically important to prevent one of the outcomes listed above.
Number of Participants with Adverse Events of Special Interests (AESIs)
时间窗: Up to 3 years
Number of participants with AESIs will be reported. Treatment-emergent AEs associated with the following situations are considered an AESI: a) infections that are severe or require intravenous (IV) anti-infective or operative/invasive intervention; b) hypoalbuminemia with albumin less than (\<)20 grams per liter (g/L) \[\<\] 2.0 grams per deciliter \[g/dL\]) c) opportunistic infections and d) Serious and non-serious deep-vein thrombosis (DVT) and/or pulmonary embolism (PE). Any AE occurring at or after the initial administration of study intervention through end of study is treatment emergent.
Number of Participants with Abnormalities in Clinical Laboratory Tests
时间窗: Up to 3 years
Number of participants with abnormalities in clinical laboratory tests (including chemistry, hematology, coagulation, and urinalysis) will be reported.
Number of Participants with Abnormalities in Vital Signs
时间窗: Up to 3 years
Number of participants with abnormalities in vital signs including sitting pulse/heart rate, sitting systolic and diastolic blood pressure, and oral temperature (degrees Celsius) will be reported.
Number of Participants with Abnormalities in Physical Examination
时间窗: Up to 3 years
Number of participants with abnormalities in physical examinations including height, weight, assessments of the skin, head, eyes, ears, nose, throat, neck, thyroid, lungs, heart, abdomen, lymph nodes and extremities will be reported.
Serum Concentration of Nipocalimab over Time
时间窗: Up to 3 years
Serum samples will be analyzed to determine concentrations of nipocalimab using a validated, specific, and sensitive immunoassay method.
Clearance (CL) of Nipocalimab
时间窗: Up to 3 years
CL is defined as the volume of serum from which nipocalimab is completely removed per unit time.
Volume of Distribution (V) of Nipocalimab
时间窗: Up to 3 years
V is defined as the representation of nipocalimab's propensity to either remain in the serum or redistribute to other tissue compartments.
Half-life (t1/2) of Nipocalimab
时间窗: Up to 3 years
t1/2 is defined as the time it takes for nipocalimab's active substance in the body to reduce by half.
Steady-state Peak Concentration (Cpeak,ss) of Nipocalimab
时间窗: Up to 3 years
Cpeak,ss is defined as the peak serum concentration of nipocalimab at steady state.
Steady-state Trough concentration (Ctrough,ss) of Nipocalimab
时间窗: Up to 3 years
Ctrough,ss will be reported. It is defined as the observed serum concentration of nipocalimab just prior to the beginning of a dosing interval at steady state.
Steady-state Area Under the Curve (AUCss) of Nipocalimab
时间窗: Up to 3 years
AUCss is defined as the area under the curve for nipocalimab at steady state.
次要结局
- Number of Participants with Anti-Drug Antibodies [ADAs] to Nipocalimab(Up to 3 years)
- Change from Baseline in Myasthenia Gravis -Activities of Daily Living (MG-ADL) Score(Up to 3 years)
- Neurological Quality of Life (Neuro-QoL) Pediatric Fatigue Score(Up to 3 years)
- Patient Global Impression of Severity (PGI-S) Score(Up to 3 years)
- Number of Participants with Neutralizing Antibodies (NAbs) to Nipocalimab(Up to 3 years)
- Change in the Quantitative Myasthenia Gravis (QMG) Score(Up to 3 years)
- Number of Participants with Vaccine Antibody Titers to Diphtheria or Tetanus(Up to 3 years)
- Patient Global Impression of Change (PGI-C) Score(Up to 3 years)
- European Quality of Life 5-Dimension Youth (EQ-5D-Y) Tool Score(Up to 3 years)