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

Phase 2

Completed

• Conditions: Postural Orthostatic Tachycardia Syndrome
• Interventions: Drug: Placebo; Drug: Efgartigimod

• Registration Number: NCT05633407
• Lead Sponsor: argenx

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.

Study Timeline

• Study Start: 2022-09-23
• Study First Submitted: 2022-11-08
• Study First Submitted QC: 2022-11-29
• Study First Posted: 2022-12-01
• Primary Completion: 2024-04-18
• Study Completion: 2024-04-18
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-02
• Last Update Posted: 2024-10-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 53

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Receive a matching placebo during weekly infusions during a treatment period of 24 weeks
Efgartigimod	Efgartigimod	Receive efgartigimod IV 10mg/kg during weekly infusions during a treatment period of 24 weeks

Primary Outcome Measures

Name	Time	Method
Evaluate the safety and tolerability of efgartigimod in patients with post-COVID-19 POTS	Up to 31 weeks	Incidence and severity of adverse events (AEs), incidence of serious adverse events (SAEs), changes in laboratory test results, vital sign measurements, and electrocardiogram (ECG) results.
Evaluate the efficacy of efgartigimod in reducing the severity of post-COVID-19 POTS symptoms	Outcome measure is assessed at baseline and week 24.	Change from baseline to week 24 in the Malmo POTS Symptom Score (MaPS).

Secondary Outcome Measures

Name	Time	Method
Evaluate the efficacy of efgartigimod on patient global assessment of disease activity and fatigue	Change from baseline to week 24	Change from baseline to week 24 in the PROMIS Cognitive Function Short Form 6a
Assess the pharmacodynamic (PD) effect of efgartigimod	From Baseline to week 24	Absolute values, changes from baseline, and percent reduction from baseline in total IgG levels
Assess the pharmacokinetic (PK) profile of efgartigimod	From Baseline to week 24	Efgartigimod serum concentration-time profile
Assess the immunogenicity of efgartigimod	From Baseline to week 24	Incidence and prevalence of antidrug antibodies (ADA) against efgartigimod

Trial Locations

Locations (11)

University of California, San Diego Sulpizio Cardiovascular Center; 🇺🇸 La Jolla, California, United States

Johns Hopkins University; 🇺🇸 Baltimore, Maryland, United States

Stanford Movement Disorder Center; 🇺🇸 Palo Alto, California, United States

Northshore University Health System; 🇺🇸 Glenview, Illinois, United States

Harvard Medical School, Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States

Texas Institute of Cardiology; 🇺🇸 McKinney, Texas, United States

Apex Trials Croup, LLC; 🇺🇸 Fort Worth, Texas, United States

Case Western Reserve University; 🇺🇸 Cleveland, Ohio, United States

Pioneer Clinical Research; 🇺🇸 Rosharon, Texas, United States

Metrodora Institute; 🇺🇸 West Valley City, Utah, United States

Vandetbilt University Medical Center / Clinical Research Center; 🇺🇸 Nashville, Tennessee, United States