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.

A Study of Nipocalimab in Children Aged 2 to Less Than 18 Years With Generalized Myasthenia Gravis

Myasthenia Gravis

Autoantibody disorders (affecting the nervous system)

Brain and Nervous System Conditions

Nipocalimab

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

Change from baseline in total serum IgG levels were reported.

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 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 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 (including
chemistry, hematology, coagulation, and urinalysis) will be reported.

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 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 samples will be analyzed to determine concentrations of nipocalimab using a
validated, specific, and sensitive immunoassay method.

CL is defined as the volume of serum from which nipocalimab is completely removed per
unit time.

V is defined as the representation of nipocalimab's propensity to either remain in the
serum or redistribute to other tissue compartments.

t1/2 is defined as the time it takes for nipocalimab's active substance in the body to
reduce by half.

Cpeak,ss is defined as the peak serum concentration of nipocalimab at steady state.

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.

AUCss is defined as the area under the curve for nipocalimab at steady state.

Change from baseline in MG-ADL score will be reported. The MG-ADL score provides a rapid
assessment of the participant's myasthenia gravis (MG) symptom severity. Eight functions
(talking, chewing, swallowing, breathing, impairment of ability to brush teeth or comb
hair, impairment of ability to arise from a chair, double vision, eyelid droop) are rated
on a 4-point scale: 0 (no impairment) to 3 (severe impairment). The total score will be
sum of eight function scores and can range from 0 to 24. A higher score indicates greater
symptom severity.

The QMG score is a standardized quantitative strength assessment comprising 13 components
(and is administered by a trained qualified healthcare professional [HCP] eg, physician,
physician assistant, nurse practitioner, nurse). The quantitative results of each
strength component are mapped to the following 4-point scale: 0 equals to (=) none, 1 =
mild, 2 = moderate and 3 = severe. The total score will be sum of 13 components scores
and can range from 0 to 39. A higher score indicates greater weakness.

The EQ-5D-Y is a standardized child friendly instrument for use as a measure of health
status, primarily designed for self-completion by children and adolescents, or via a
proxy version to be completed by the child's caregiver. The EQ-5D-Y descriptive system
comprises the following 5 dimensions: Mobility, looking after myself (washing and
dressing), usual activities, pain or discomfort and feeling worried or unhappy. Each of
the 5 dimensions is divided into 3 levels of perceived problems (Level 1 indicating no
problem, Level 2 indicating some problems, Level 3 a lot of problems).

The Neuro-QoL pediatric fatigue score will be used to assess the impact of fatigue in
participants aged 10 to less than (<) 18 years. The participant will rate each of the 11
items on a 5-point scale. Higher scores indicate greater fatigue.

The PGI-S score will be used to assess the severity of fatigue due to generalized
myasthenia gravis (gMG) in participants aged 10 to < 18 years. Participants will be asked
to rate their fatigue over the past 7 days using the following 5-point scale: 1 = None, 2
= Mild, 3 = Moderate, 4 = Severe, and 5 = Very severe. Higher scores indicate greater
severity of fatigue.

The PGI-C score will be used to assess if there has been an improvement or decline in
patient-reported fatigue since the beginning of the treatment in participants aged 10 to
<18 years. Participants will be asked to rate their current fatigue as compared to when
they started the study, using the following 7-point scale: 1 = Much better, 2 =
Moderately better, 3 = A little better, 4 = No change, 5 = A little worse, 6 = Moderately
worse, and 7 = Much worse. Higher scores indicate greater change in overall fatigue.

Number of participants with ADAs to nipocalimab will be reported.

Number of participants with NAbs to nipocalimab will be reported.

Number of participants with vaccine antibody titers to diphtheria or tetanus will be
reported.

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).

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, 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.

Phoenix Children's Hospital

Lucile Packard Children's Hospital Stanford

UCSF Benioff Children's Hospital

Children's Hospital Colorado

University of South Florida Morsani Center for Advanced Healthcare

University of Kansas Medical Center

C.S. Mott Children's Hospital

Childrens Hospital Of Philadelphia

Nagano Children's Hospital

Chiba University Hospital

University of Miyazaki Hospital

Saitama Prefecture Children's Medical Center

Tokyo Women's Medical University Hospital

Leiden University Medical Center

Change from baseline in total serum IgG antibodies levels were reported.

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 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 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]) and c) opportunistic infections. 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 (including chemistry, hematology, coagulation, and urinalysis) will be reported.

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 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 samples will be analyzed to determine concentrations of nipocalimab using a validated, specific, and sensitive immunoassay method.

CL is defined as the volume of serum from which nipocalimab is completely removed per unit time.

V is defined as the representation of nipocalimab's propensity to either remain in the serum or redistribute to other tissue compartments.

t1/2 is defined as the time it takes for nipocalimab's active substance in the body to reduce by half.

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.

Change from baseline in MG-ADL score will be reported. The MG-ADL score provides a rapid assessment of the participant's myasthenia gravis (MG) symptom severity. Eight functions (talking, chewing, swallowing, breathing, impairment of ability to brush teeth or comb hair, impairment of ability to arise from a chair, double vision, eyelid droop) are rated on a 4-point scale: 0 (no impairment) to 3 (severe impairment). The total score will be sum of eight function scores and can range from 0 to 24. A higher score indicates greater symptom severity.

The QMG score is a standardized quantitative strength assessment comprising 13 components (and is administered by a trained qualified healthcare professional [HCP] eg, physician, physician assistant, nurse practitioner, nurse). The quantitative results of each strength component are mapped to the following 4-point scale: 0 equals to (=) none, 1 = mild, 2 = moderate and 3 = severe. The total score will be sum of 13 components scores and can range from 0 to 39. A higher score indicates greater weakness.

The EQ-5D-Y is a standardized child friendly instrument for use as a measure of health status, primarily designed for self-completion by children and adolescents, or via a proxy version to be completed by the child's caregiver. The EQ-5D-Y descriptive system comprises the following 5 dimensions: Mobility, looking after myself (washing and dressing), usual activities, pain or discomfort and feeling worried or unhappy. Each of the 5 dimensions is divided into 3 levels of perceived problems (Level 1 indicating no problem, Level 2 indicating some problems, Level 3 a lot of problems).

The Neuro-QoL pediatric fatigue score will be used to assess the impact of fatigue in participants aged 10 to less than (<) 18 years. The participant will rate each of the 11 items on a 5-point scale. Higher scores indicate greater fatigue.

The PGI-S score will be used to assess the severity of fatigue due to generalized myasthenia gravis (gMG) in participants aged 10 to < 18 years. Participants will be asked to rate their fatigue over the past 7 days using the following 5-point scale: 1 = None, 2 = Mild, 3 = Moderate, 4 = Severe, and 5 = Very severe. Higher scores indicate greater severity of fatigue.

The PGI-C score will be used to assess if there has been an improvement or decline in patient-reported fatigue since the beginning of the treatment in participants aged 10 to <18 years. Participants will be asked to rate their current fatigue as compared to when they started the study, using the following 7-point scale: 1 = Much better, 2 = Moderately better, 3 = A little better, 4 = No change, 5 = A little worse, 6 = Moderately worse, and 7 = Much worse. Higher scores indicate greater change in overall fatigue.

Number of participants with vaccine antibody titers to diphtheria or tetanus will be reported.

Participants aged 2 to less than [<] 18 years of age 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).

A Study of Nipocalimab in Children Aged 2 to Less Than 18 Years With Generalized Myasthenia Gravis

Trials at a glance

Trials at a glance

A Study of Nipocalimab in Children Aged 2 to Less Than 18 Years With Generalized Myasthenia Gravis

Outcome measures

Primary outcome measures

Secondary outcome measures