| Eligibility |
Inclusion criteria:
1. The subject is between 18 to 65 years of age, inclusive, at the time the informed
consent form (ICF) is signed.
2. The subject is either male, or female of nonchildbearing potential. Females in the
following categories are considered a woman of nonchildbearing potential:
1. Postmenopausal female: A postmenopausal state is defined as continuous amenorrhea
for at least 1 year without an alternative medical cause and a
follicle-stimulating hormone (FSH) measurement of >40 IU/L. A historical
pretreatment FSH measurement of>40 IU/L is accepted as proof of a postmenopausal
state for subjects on hormone replacement therapy.
2. Surgically sterile female: women who have had a documented permanent
sterilization procedure (ie, hysterectomy, bilateral salpingectomy, or bilateral
oophorectomy).
3. Female subjects must have a negative serum pregnancy test on day -1 before IMP can be
administered.
4. The subject has a body mass index (BMI) within the range 18 to 30 kg/m2 and body
weight 50 to 100 kg (inclusive) before IMP administration.
5. The subject is able to understand the requirements of the study and provide written
informed consent (including consent for the use and disclosure of research-related
health information), and is willing and able to comply with the study protocol
procedures (including the required study visits).
6. The subject is in good physical and mental health, per the opinion of the
investigator, based on medical history; physical examination findings; ECG recordings;
vital sign measurements; systemic lupus erythematous (SLE) panel results; and
biochemistry, hematology, INR, and urinalysis laboratory test results prior to the
first dose of IMP on day 1.
7. Nonsterilized male subjects who are sexually active with a female partner of
childbearing potential must use effective contraception from the signing of the ICF
through 260 days after the last IMP administration. A male subject practicing true
sexual abstinence (as consistent with the preferred and usual lifestyle) can be
included. Sterilized male subjects who have had a vasectomy and with documented
absence of sperm post-procedure can be included. Male subjects are not allowed to
donate sperm from signing of the ICF through 260 days after the last dose of IMP.
8. The subject has abdominal skin that, in the opinion of the investigator, allows for
the absorption and localized safety assessment of SC administration (applicable for
dose levels with SC administration only).
9. The subject agrees to discontinue and refrain from the use of all medications,
including nonprescription and/or prescription medications, for at least 2 weeks before
the first dose of IMP through the EOS visit on day 260 (Part A [SAD]), day 288 (Part B
[MAD], cohorts 1 through 5). The occasional use of paracetamol at doses up to 2 g/day
with a maximum of 10 g/2 weeks is allowed upon approval from the investigator.
COVID-19 immunization recommendations are described in Section 4.3.1.1.
10. The subject is a nonsmoker and does not use any nicotine-containing products. A
nonsmoker is defined as an individual who has abstained from smoking for at least 3
months prior to screening.
11. The subject has a negative urine drug and alcohol screen for amphetamines,
barbiturates, benzodiazepines, cannabis, cocaine, opiates, methadone, tricyclic
antidepressants and alcohol at screening and on day -1.
12. The subject has a body temperature of 35.5 °C to 37.6 °C at screening and prior to the
first dose of IMP day 1.
Exclusion criteria:
1. The subject has a known hypersensitivity to any of the components of the IMP, or, in
the opinion of the investigator, a history of a significant allergic reaction to any
drug.
2. The subject has previously participated in a clinical study with efgartigimod and was
administered an IMP.
3. The subject has a positive serum test at screening for an active viral infection with
any of the following conditions:
1. Hepatitis B virus (HBV) that is indicative of an acute or chronic infection
(https://www.cdc.gov/hepatitis/HBV/PDFs/SerologicChartv8.pdf)
2. Hepatitis C virus (HCV) based on HCV antibody assay
3. Human immunodeficiency virus
4. The subject tests positively at screening for SLE as determined by the SLE test panel.
5. The subject has a known family history of SLE.
6. The subject has known clinically relevant immunological disorders.
7. The subject has a history of severe allergic or anaphylactic reactions.
8. The subject has clinical evidence of significant serious diseases, underwent a recent
major surgery, or has any other condition that, in the opinion of the investigator,
could confound the results of the study or put the subject at undue risk. The
conditions and diseases that will lead to subject exclusion include recognized
uncontrolled risk factors associated with acute respiratory distress syndrome (ARDS)
and death in subjects with COVID-19 (eg, hypertension, diabetes, asthma, or chronic
obstructive pulmonary disease [COPD]).
9. The subject has a clinically significant uncontrolled active or chronic bacterial,
viral, or fungal infection at screening.
10. The subject has the presence or sequelae of gastrointestinal, liver, kidney, or other
conditions known to potentially interfere with the absorption, distribution,
metabolism, or excretion of IMP.
11. The subject has an estimated glomerular filtration rate of <80 mL/min/1.73 m²
(calculated per the Chronic Kidney Disease Epidemiology Collaboration method) at
screening.
12. The subject has a history of malignancy except for:
1. Adequately treated basal cell or squamous cell skin cancer
2. Carcinoma in situ of the cervix
13. The subject has known genetic deficiencies for the complement cascade system.
14. The subject has clinically relevant abnormalities detected on an ECG that are related
to either rhythm or conduction (eg, QTcF >450 ms for male and QTcF >470 ms for female
subjects, or a known long QT syndrome).
15. The subject has clinically relevant vital sign abnormalities before the first dose of
IMP.
16. The subject had significant blood loss, including blood donation >500 mL, or
transfusion of any blood product within 12 weeks before the first dose of IMP, or the
subject has a scheduled transfusion within 4 weeks after the end of the study.
17. The subject has received treatment with any drug known to have a well-defined
potential for toxicity to a major organ in the last 3 months before the first dose of
IMP.
18. The subject has a history of any of the following:
1. consuming more than 21 units of alcoholic beverages per week (Note: 1 unit is 330
mL of beer, 110 mL of wine, or 28 mL of spirits)
2. alcoholism or drug, chemical, substance abuse within 2 years before screening
3. consuming a large quantity (>6 cups per day) of coffee, tea, or the equivalent in
the 4 weeks before the first dose of IMP.
19. The subject is concurrently participating or has participated, within 90 days before
the first dose of IMP or, if known, 5 half-lives of the investigational drug
(whichever is longer), in any drug/device or biologic investigational research study.
20. The subject has been administered any systemic immunosuppressant agent within 6 months
prior to the first dose of IMP.
21. The subject has been administered any systemic steroid within 3 months prior to the
first dose of IMP.
22. The subject is an investigator, subinvestigator, research assistant, pharmacist, study
coordinator, or other staff or relative of study personnel directly involved with the
conduct of the study.
23. The subject has any condition or circumstances that, in the opinion of the
investigator, may make a subject unlikely or unable to complete the study or comply
with study procedures and requirements.
24. The subject is a pregnant or lactating female, or intends to become pregnant during
the study or within 260 days after the last dose of IMP.
25. The subject has any condition that impairs phlebotomy.
26. The subject has a positive nasopharyngeal polymerase chain reaction (PCR) test for
SARS-CoV-2 on day -2 or -1.
27. The subject has any contact with anyone who has tested positive for SARS-CoV-2 or
COVID-19 within the last 2 weeks prior to admission to the clinical research center.
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