Clinical trial NCT05633407: Efficacy and Safety Study of Efgartigimod in Adults With Post-COVID-19 POTS
Official title: A Phase 2 Randomized, Double-blinded, Placebo-controlled Study to Evaluate the Efficacy and Safety of Efgartigimod IV in Adult Patients With Post-COVID-19 Postural Orthostatic Tachycardia Syndrome (POTS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Postural Orthostatic Tachycardia Syndrome
Keywords: POTS
Long COVID
Postural Orthostatic Tachycardia Syndrome
efgartigimod
Lead sponsor: argenx
Sponsor class: INDUSTRY
Collaborators: name: Iqvia Pty Ltd
First posted: 2022-12-01
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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). Efgartigimod may be a viable treatment option for individuals diagnosed with post-COVID-19 POTS because it has been shown to reduce IgG levels, including IgG autoantibodies, which may underlie some of the autonomic disease manifestations in these patients.

Eligibility criteria: Inclusion Criteria:

1. Reached the age of consent when signing the informed consent form
2. Capable of providing signed informed consent and complying with protocol requirements
3. Diagnosed with new-onset POTS post-COVID-19 established by the following:

   1. History of COVID-19 based on a previous positive test result from either laboratory-confirmed COVID-19 test (eg, a PCR test) or non-laboratory-confirmed COVID-19 test (eg, rapid antigen test); this positive result may be either documented or patient-reported
   2. Tilt 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)
   3. 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 diaphoresis
4. COMPASS 31 ≥35 at screening
5. Agree to use contraceptives consistent with local regulations regarding the methods of contraception for those participating in clinical studies and the following:

   Male participants: No male contraception is required 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.
6. Body mass index (BMI) \<35 kg/m2

Exclusion Criteria:

1. 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 exam
2. History 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 myopathy
3. Known 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 risk
4. Known HIV disease or common variable immunodeficiency
5. History 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:

   1. Basal cell or squamous cell skin cancer
   2. Carcinoma in situ of the cervix
   3. Carcinoma in situ of the breast
   4. Incidental histological finding of prostate cancer (TNM stage T1a or T1b)
6. Clinically significant uncontrolled active or chronic bacterial, viral, or fungal infection or positive SARS-CoV-2 PCR test at screening
7. Positive serum test at screening for an active infection with any of the following:

   1. 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 test
   2. Hepatitis C virus (HCV) based on HCV antibody assay unless a negative RNA test is available
   3. HIV
8. A medical condition that could confound the results of the study or put the participant at undue risk in the investigator's judgment
9. Clinically 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 risk
10. Total IgG \<4 g/L at screening
11. Received within 12 weeks or 5 half-lives (whichever is longer) before screening an investigational product
12. Received within 12 weeks before screening either intravenous immunoglobulin (Ig) IV or SC or plasmapheresis/plasma exchange (PLEX)
13. Received a live or live-attenuated vaccine less than 4 weeks before screening
14. Known hypersensitivity to IMP or 1 of its excipients
15. Previously participated in an efgartigimod clinical study and received at least 1 dose of IMP
16. Currently participating in another interventional clinical study
17. History (within 12 months of screening) of or current alcohol, drug, or medication abuse
18. Pregnant or lactating or intends to become pregnant during the study
19. Unwilling to remain on a stable regimen of medications during the study
20. Unwilling to avoid initiation of new physical rehabilitation or other physician-prescribed exercise programs during the 24-week treatment period

Primary outcomes:
measure: Change From Baseline to Week 24 in the COMPASS 31 (2-week Recall Version)
timeFrame: Baseline (Day 1) and Week 24
measure: Change From Baseline to Week 24 in the MaPS
timeFrame: Baseline (Day 1) and Week 24
measure: Number of Participants With TEAEs and TESAEs
timeFrame: From the first dose of study drug (Day 1) up to 60 days post last dose of study drug, up to 236 days
Secondary outcomes:
measure: Percentage of Participants With Improved PGI-S at Week 24
timeFrame: Baseline (Day 1) and Week 24
measure: Percentage of Participants With Improved in PGI-C at Week 24
timeFrame: Baseline (Day 1) and Week 24
measure: Change From Baseline to Week 24 in the PROMIS Fatigue Short Form 8a
timeFrame: Baseline (Day 1) and Week 24
measure: Change From Baseline to Week 24 in the PROMIS Cognitive Function Short Form 6a
timeFrame: Baseline (Day 1) and Week 24
measure: Percent Change From Baseline in Total IgG Levels at Week 24
timeFrame: Baseline (Day 1) and Week 24
measure: Serum Concentration of Efgartigimod
timeFrame: Pre-dose and post-dose at Baseline (Day 1), Weeks 1, 4, 12 and at Week 24
measure: Number of Participants With ADAs Against Efgartigimod
timeFrame: Up to Week 24
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California, San Diego Sulpizio Cardiovascular Center
state: California
city: Palo Alto
country: United States
facility: Stanford Movement Disorder Center
state: California
city: Glenview
country: United States
facility: Northshore University Health System
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Harvard Medical School, Brigham and Women's Hospital
state: Massachusetts
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Nashville
country: United States
facility: Vandetbilt University Medical Center / Clinical Research Center
state: Tennessee
city: Fort Worth
country: United States
facility: Apex Trials Croup, LLC
state: Texas
city: McKinney
country: United States
facility: Texas Institute of Cardiology
state: Texas
city: Rosharon
country: United States
facility: Pioneer Clinical Research
state: Texas
city: West Valley City
country: United States
facility: Metrodora Institute
state: Utah
Study officials:
References: