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

1. Boy or girl 2 to <18 years of age.
2. Diagnosis of MG with generalized muscle weakness meeting the clinical
criteria for gMG as defined by the MGFA Clinical Classification Class IIa/b,
IIIa/b, or IVa/b at screening
3. Has a positive serologic test for acetylcholine receptor (anti-AChR)
antibodies or muscle-specific tyrosine kinase (anti-MuSK) antibodies at
screening.
4. Has suboptimal response to current stable therapy for gMG according to the
investigator. Stable therapy is defined as the following, as applicable to
their specific therapy(ies):
a. If taking an acetylcholinesterase inhibitor, the participant must have been
on a stable dose and regimen for at least 2 weeks prior to screening. Changes
to the dose of
acetylcholinesterase inhibitors may be permitted if medically necessary during
any phase of the trial.
b. If taking a glucocorticosteroid, the participant must have been on a stable
dose and regimen for at least 4 weeks prior to baseline.
c. If currently receiving immunosuppressants, the participant must have been on
the given immunosuppressant for >=6 months and on a stable dose for >=3 months
prior to
baseline. Allowed concomitant immunosuppressants are azathioprine,
mycophenolate mofetil/mycophenolic acid, methotrexate, cyclosporine, tacrolimus,
or cyclophosphamide.
OR
Has discontinued corticosteroids and/or immunosuppressants/immunomodulators
including eculizumab or other novel approved immune agents at least 4 weeks
prior to screening due to intolerance or lack of efficacy.

Note: All above background medications must be optimized and unchanged for the
duration specified in Criteria #4 prior to screening and/or baseline visits.
Investigators are encouraged to consider all treatment escalation options,
including thymectomy, prior to enrolling. Participants started on new
treatments must meet the above stable dose duration rules, and cannot meet
exclusion criterion #6 as defined in Section 5.2.

5. 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
6. Participants who have undergone splenectomy (if local regulatory authority
has not requested exclusion of participants with splenectomy) must be at least
3 months post resection prior to screening and must be vaccinated as per the
United States Center for Disease Control and
Prevention annual Recommended Immunization Schedule for Ages 18 years or
younger, United States. (www.cdc.gov) OR must be vaccinated as per
territory-specific guidelines or local regulations.
Note: This criterion is not applicable if splenectomy is excluded by the local
authority.
7. Has sufficient venous access to allow drug administration by infusion and
blood sampling as per the protocol.
8. Is recommended to be up to date on all age-appropriate vaccinations (eg
diphtheria and tetanus) prior to screening as per routine local medical
guidelines. It is strongly recommended that participants, as applicable, will
have completed a locally-approved (or emergency use-authorized) COVID-19
vaccination regimen and it should be at least 2 weeks prior to study-related
visits or procedures. Study participants should follow applicable local vaccine
labeling, guidelines, and standards-of-care for patients receiving
immune-targeted therapy when determining an appropriate interval between
vaccination and study enrollment. (see also Section 6.8.3).

Weight
9. 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.

Sex and Contraceptive/Barrier Requirements
10. Criterion removed per Amendment 1.
11. A female of childbearing potential must have a negative highly sensitive
serum (*-human chorionic gonadotropin [*-hCG]) at Screening and a negative
urine pregnancy test at Day 1 prior to administration of study intervention.
12. A female must be (as defined in Section 10.6, Appendix 6: Contraceptive and
Barrier Guidance.)
a. Not of childbearing potential, or
b. Of childbearing potential and
Sexual abstinence is strongly recommended; however heterosexually active
female participants must practice a highly effective, preferably user
independent method of contraception (failure rate of <1% per year when used
consistently and correctly) and agree to remain on a highly effective method
while receiving study intervention and until 30 days after last dose
- the end of relevant systemic exposure. The investigator should evaluate the
potential for contraceptive method failure (eg, noncompliance, recently
initiated) in relationship to the first dose of study intervention. Examples of
highly effective methods of contraception are located in Section 10.6,
Appendix 6: Contraceptive and Barrier Guidance.
Note: Labeling requirements of concomitant treatment a participant is
currently receiving
will supersede if more stringent.
13. Female participants of childbearing potential must agree not to donate or
freeze eggs (ova,
oocytes), for future use for the purposes of assisted reproduction, during the
study and for
a period of 30 days after the administration of study intervention.
14. 14.1 Sexual abstinence is strongly recommended; however, heterosexually
active
post-pubertal male participants must wear a condom when engaging in any
activity that
allows for passage of ejaculate to another person during the study and for at
least 90 days
after receiving the last administration of study intervention. In addition,
male participants
with partners who are females of childbearing potential are highly encouraged
to inform
their partner to use highly effective contraception methods that result in a
low failure rate
(less than 1% per year). See Section 10.6, Appendix 6: Contraceptive and Barrier
Guidance.
15. A post-pubertal male participant must agree not to donate sperm for the
purpose of
reproduction during the study and for a minimum 90 days after receiving the last
administration of study intervention.

Informed Consent
16. A legal guardian (as defined in Section 2. Introduction) must sign an
informed consent
form (ICF) indicating that he or she understands the purpose of, and procedures
required
for, the study and is willing to participate in the study. Parent(s)
(preferably both if
available or as per local requirements) [(or their legally acceptable
representative)] must
sign an ICF indicating that he or she understands the purpose of, and
procedures required
for, the study and is willing to allow the child to participate in the study.
Assent is also
required of children capable of understanding the nature of the study
(typically 7 years of
age and older) as described in Section 10.4.3, Appendix 4: Regulatory, Ethical,
and Study
Oversight Considerations
17. A legal guardian or primary caregiver must be available to help the
study-site personnel
ensure follow-up; accompany the participant to the study site on each
assessment day
according to the SoA; consistently and consecutively be available to provide
information
on the participant using the rating scales during the scheduled study visits.

1. Has a history of severe and/or uncontrolled hepatic (eg,
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) (eg, diabetes
mellitus), or
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.
Note: Any condition for which, in the opinion of the investigator,
participation would
not be in the best interest of the participants (eg, compromise well-being) or
that could
prevent, limit, or confound the protocol-specified assessments.
2. 3.1 Has MGFA Class I disease or presence of MG crisis (MGFA Class V) at
screening,
history of MG crisis within 1 month of screening, or fixed weakness (and/or
*burnt out*
MG). (Note: Participants should not be actively deteriorating at the screening
or
baseline visit such that they meet the criteria for Clinical Deterioration as
defined in
Section 6.8.2).
3. Has MGFA Class I disease or presence of MG crisis (MGFA Class V) at
screening,
history of MG crisis within 1 month of screening, or fixed weakness (and/or
*burnt out*
MG).
Note: Participants should not be actively deteriorating at the screening or
baseline visit such that they meet the criteria for Clinical Deterioration as
defined in
Section 6.8.2.
4. Is dependent on gastric tube for nutritional needs or is
ventilator-dependent.
5. Is actively undergoing radiation or chemotherapy for an unresected
thymoma/malignant
thymoma. Participants with stable, benign thymoma (stage I or IIa, for example)
for
which no treatment has been undertaken in the past 3 years may be allowed
following
discussion with the sponsor*s medical monitor.
6. Has had a thymectomy within 12 months prior to screening, or thymectomy is
planned
during the Active treatment Phase of the study.
7. Has current or a history of any neurologic disorder other than MG that might
interfere
with the accuracy of study assessments, including but not limited to any chronic
neurodegenerative disease, altered level of consciousness, dementia, abnormal
mental
status, major congenital neurologic defect, Lambert-Eaton myasthenic syndrome,
drug
induced MG, or hereditary forms of myasthenic syndrome.
8. Currently has a malignancy or has a history of malignancy within 3 years
before
screening (with the exception of localized basal cell carcinoma and/or squamous
cell
carcinoma skin cancer that has been adequately treated with no evidence of
recurrence
for at least 3 months [defined as a minimum of 12 weeks] before the first study
intervention administration or cervical carcinoma in situ that has been treated
with no
evidence of recurrence for at least 3 months before the first study intervention
administration).
9. Has known allergies, hypersensitivity, or intolerance to nipocalimab or its
excipients
(refer to the IB).
10. Has shown a previous severe immediate hypersensitivity reaction, such as
anaphylaxis
to therapeutic proteins (eg, monoclonal antibodies).
11. Has experienced myocardial infarction, unstable ischemic heart disease, or
stroke
within 12 weeks of screening.
12. A post-pubertal male participant is planning to father a child while
enrolled in this
study or donate sperm within 90 days after the last administration of study
intervention.
13.
13.1 A female of childbearing potential is currently breastfeeding, pregnant,
intends to
become pregnant during the study, or is planning egg donation during the study
or
within 30 days after the last dose of study intervention.
14. History of moderate or severe substance or alcohol use disorder according
to Diagnostic
and Statistical Manual of Mental Disorders (5th edition) (DSM-5) criteria,
except
nicotine or caffeine, within 1 year before Screening.
Prior/Concomitant Therapy
15. Is currently taking eculizumab or other novel immune agents, IgG Fc-related
protein therapeutics, or Fc-conjugated therapeutic agents, including factor or
enzyme
replacement.
16. Has received, rituximab within 6 months prior to first administration of
study
intervention.
17. Has received or is expected to receive a live vaccine within 4 weeks
prior to
screening or has a known need to receive a live vaccine during the study, or
within
8 weeks after the last administration of study intervention. For the Bacille
CalmetteGuerin
(BCG) vaccine, see exclusion criterion 33. Participants are allowed to receive a
vaccine conditionally approved by their regional health advisory for emergency
use for
severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), unless it is a
live
vaccine. Concomitant enrollment in an investigational trial for any SARS-CoV-2
(COVID-19) vaccine while participating in this study is not permitted.
18. Has received plasmapheresis, immunoadsorption therapy, or IVIg within 4
weeks prior
to baseline.
19. Has another medical condition that requires oral or parenteral
corticosteroids unless the
dose has been stable for at least 4 weeks prior to baseline and is expected to
remain
stable during the study. Inhaled, intra-articular, topical or ocular
corticosteroids are not
exclusionary.
20. Has another medical condition that requires an immunosuppressive agent
unless the
medication has been used for at least 6 months, the dose has been stable for at
least
3 months prior to baseline and the medication and the dose are expected to
remain stable
during the study.
21. Has previously received nipocalimab.
22. Has received an investigational intervention (including investigational
vaccines) within
3 months or 5 half-lives (whichever is longer) or used an invasive
investigational
medical device within 3 months before the planned first dose administration of
study
intervention [or is currently enrolled in an investigational study].
Participants are
allowed to receive a vaccine conditionally approved by their regional health
advisory
for emergency use for SARS-CoV-2.
23. Has a severe infection including opportunistic infections (eg, pneumonia,
biliary tract
infection, diverticulitis, Clostridium difficile infection, cytomegalovirus,
pneumocystosis, aspergillosis, etc.) requiring parenteral anti-infectives and/or
hospitalization, and/or is assessed as serious/clinically significant by the
Investigator,
within 8 weeks prior to Screening. The participant may be re-screened after the
8-week
exclusionary period has passed.
24. Has a chronic infection (eg, bronchiectasis, chronic osteomyelitis, chronic
pyelonephritis) or requires chronic treatment with anti-infectives (eg,
antibiotics,
antivirals).
25. Tests positive for hepatitis B virus (HBV) infection (see Section 10.3,
Appendix 3:
Hepatitis B Virus (HBV) Screening with HBV DNA).
26.
Is seropositive for antibodies to hepatitis C virus (HCV), unless they satisfy
1 of the
following conditions:
Has a history of successful treatment, defined as being negative for HCV RNA
at least 24 weeks after completing antiviral treatment, and has a negative HCV
RNA test result at screening,
OR
While seropositive, has a negative HCV RNA test result at least 24 weeks prior
to screening and a negative HCV RNA test at screening.
27. History of human immunodeficiency virus (HIV)1 or HIV2 antibody-positive, or
tests positive for HIV at screening.
28. COVID-19 infection:
During the 6 weeks prior to baseline, have had ANY of
(a) confirmed SARS-CoV-2 (COVID 19) infection (test positive), OR
(b) suspected SARS-CoV-2 infection (clinical features without documented test
results), OR
(c) close contact with a person with known or suspected SARS-CoV-2 infection:
Exception: may be included with a documented negative result for a validated
SARS
CoV-2 test
* obtained at least 2 weeks after conditions (a), (b), (c) above (timed from
resolution of key c