Efficacy and Safety Study of Efgartigimod in Adults With Post-COVID-19 POTS

The study aims to investigate the safety, tolerability, efficacy, pharmacodynamics (PD), pharmacokinetics (PK), and immunogenicity of efgartigimod compared to placebo in participants with post-COVID-19 postural orthostatic tachycardia syndrome (POTS) (post-COVID-19 POTS).

Inclusion Criteria:Reached the age of consent when signing the informed consent formCapable of providing signed informed consent and complying with protocol requirementsDiagnosed with new-onset POTS post-COVID-19 established by the following:Prior COVID-19 confirmed by documentation of historical PCR testTilt table or orthostatic vital sign measurements during screening consistent with consensus criteria: sustained HR increase of ≥30 bpm within 10 min of standing or head up tilt (≥40 bpm for individuals aged 18 to 19 years) and/or HR reaching >120 bpm within 10 min; absence of sustained 20 mmHg decrease in systolic blood pressure (SBP)Ongoing symptoms of POTS confirmed by the investigator with at least 3 symptoms in each of the following areas lasting longer than 12 weeks after either diagnosis of COVID-19 or after hospital discharge for COVID-19:i. Vasomotor symptoms: fatigue, orthostatic intolerance, brain fog, exertional dyspnea, difficulty with concentration, venous pooling, and exercise intolerance ii. Sympathetic over-compensation symptoms: palpitation, heat intolerance, nausea with or without vomiting, insomnia, anxiety, lack of appetite, chest pain, and diaphoresisCOMPASS 31 ≥35 at screeningAgree to use contraceptives consistent with local regulations regarding the methods of contraception for those participating in clinical studies and the following:Male participants Female participants of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline before receiving IMP. Contraceptive requirements.Body mass index (BMI) <35 kg/m2Exclusion Criteria:Diagnosis of or receiving treatment for the following conditions before COVID-19: peripheral neuropathy, POTS, myalgic encephalomyelitis encephalitis/chronic fatigue syndrome, Ehlers Danlos syndrome confirmed by genetic testing, autonomic neuropathy, multiple sclerosis, stroke, spinal cord injury, or any known lesions in the central nervous system by imaging or neurological examHistory of or currently being treated for clinically significant ongoing cardiac arrythmia, heart failure, myocarditis, pulmonary embolism requiring anticoagulation, pulmonary fibrosis, or critical illness-related polyneuropathy or myopathyKnown autoimmune disease that, in the investigator's judgment, would interfere with an accurate assessment of clinical symptoms of post-COVID-19 POTS or puts the participant at undue riskKnown HIV disease or common variable immunodeficiencyHistory of malignancy unless considered cured by adequate treatment with no evidence of recurrence for ≥3 years before the first administration of IMP. Adequately-treated participants with the following cancers may be included at any time:Basal cell or squamous cell skin cancerCarcinoma in situ of the cervixCarcinoma in situ of the breastIncidental histological finding of prostate cancer (TNM stage T1a or T1b)Clinically significant uncontrolled active or chronic bacterial, viral, or fungal infection or positive SARS-CoV-2 PCR test at screeningPositive serum test at screening for an active infection with any of the following:Hepatitis B virus (HBV) that is indicative of an acute or chronic infection, unless associated with a negative HB surface antigen (HBsAg) or negative HBV DNA testHepatitis C virus (HCV) based on HCV antibody assay unless a negative RNA test is availableHIVA medical condition that could confound the results of the study or put the participant at undue risk in the investigator's judgmentClinically significant disease, recent major surgery (within 3 months of screening), or intends to have surgery during the study; or any other condition that in the opinion of the investigator could confound the results of the study or put the participant at undue riskTotal IgG <4 g/L at screeningReceived within 12 weeks or 5 half-lives (whichever is longer) before screening an investigational productReceived within 12 weeks before screening either intravenous immunoglobulin (Ig) IV or SC or plasmapheresis/plasma exchange (PLEX)Received a live or live-attenuated vaccine less than 4 weeks before screeningKnown hypersensitivity to IMP or 1 of its excipientsPreviously participated in an efgartigimod clinical study and received at least 1 dose of IMPCurrently participating in another interventional clinical studyHistory (within 12 months of screening) of or current alcohol, drug, or medication abusePregnant or lactating or intends to become pregnant during the studyUnwilling to remain on a stable regimen of medications during the studyUnwilling to avoid initiation of new physical rehabilitation or other physician-prescribed exercise programs during the 24-week treatment period