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

• ClinicalTrials.gov Identifier: NCT05633407
• Recruitment Status: Completed
• First Posted: December 1, 2022
• Last Update Posted: May 7, 2024
• Sponsor: argenx
• Collaborator: Iqvia Pty Ltd
• Information provided by (Responsible Party): argenx

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Postural Orthostatic Tachycardia Syndrome	Drug: Efgartigimod; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 53 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: September 23, 2022
• Actual Primary Completion Date: April 18, 2024
• Actual Study Completion Date: April 18, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Efgartigimod; Receive efgartigimod IV 10mg/kg during weekly infusions during a treatment period of 24 weeks	Drug: Efgartigimod; Efgartigimod IV 10 mg/kg infusion qw for 24 weeks. Participants will be randomized to receive efgartigimod IV 10 mg/kg or matching placebo in a 2:1 ratio, respectively
Placebo Comparator: Placebo; Receive a matching placebo during weekly infusions during a treatment period of 24 weeks	Drug: Placebo; Receive a matching placebo during weekly infusions during a treatment period of 24 weeks. Participants will be randomized to receive efgartigimod IV 10 mg/kg or matching placebo in a 2:1 ratio, respectively

Outcome Measures

Primary Outcome Measures :

1. Evaluate the efficacy of efgartigimod in reducing the severity of post-COVID-19 POTS symptoms [ Time Frame: Outcome measure is assessed at baseline and week 24. ]
   Change from baseline to week 24 in the Composite Autonomic Symptom Score 31 (COMPASS 31).
2. Evaluate the efficacy of efgartigimod in reducing the severity of post-COVID-19 POTS symptoms [ Time Frame: Outcome measure is assessed at baseline and week 24. ]
   Change from baseline to week 24 in the Malmo POTS Symptom Score (MaPS).
3. Evaluate the safety and tolerability of efgartigimod in patients with post-COVID-19 POTS [ Time Frame: 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.

Secondary Outcome Measures :

1. Evaluate the efficacy of efgartigimod on patient global assessment of disease activity and fatigue [ Time Frame: Change from baseline to week 24 ]
   Change from baseline to week 24 in the Patient Global Impression of Severity (PGI-S)
2. Evaluate the efficacy of efgartigimod on patient global assessment of disease activity and fatigue [ Time Frame: Change from baseline to week 24 ]
   Change from baseline to week 24 in the Patient Global Impression of Change (PGI-C)
3. Evaluate the efficacy of efgartigimod on patient global assessment of disease activity and fatigue [ Time Frame: Change from baseline to week 24 ]
   Change from baseline to week 24 in the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form 8a
4. Evaluate the efficacy of efgartigimod on patient global assessment of disease activity and fatigue [ Time Frame: Change from baseline to week 24 ]
   Change from baseline to week 24 in the PROMIS Cognitive Function Short Form 6a
5. Assess the pharmacodynamic (PD) effect of efgartigimod [ Time Frame: From Baseline to week 24 ]
   Absolute values, changes from baseline, and percent reduction from baseline in total IgG levels
6. Assess the pharmacokinetic (PK) profile of efgartigimod [ Time Frame: From Baseline to week 24 ]
   Efgartigimod serum concentration-time profile
7. Assess the immunogenicity of efgartigimod [ Time Frame: From Baseline to week 24 ]
   Incidence and prevalence of antidrug antibodies (ADA) against efgartigimod

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, California

University of California, San Diego Sulpizio Cardiovascular Center

La Jolla, California, United States, 92037

Stanford Movement Disorder Center

Palo Alto, California, United States, 94304

United States, Illinois

Northshore University Health System

Glenview, Illinois, United States, 60026

United States, Maryland

Johns Hopkins University

Baltimore, Maryland, United States, 21224

United States, Massachusetts

Harvard Medical School, Brigham and Women's Hospital

Boston, Massachusetts, United States, 02115

United States, Ohio

Case Western Reserve University

Cleveland, Ohio, United States, 44106

United States, Tennessee

Vandetbilt University Medical Center / Clinical Research Center

Nashville, Tennessee, United States, 37232

United States, Texas

Apex Trials Croup, LLC

Fort Worth, Texas, United States, 76132

Texas Institute of Cardiology

McKinney, Texas, United States, 75071

Pioneer Clinical Research

Rosharon, Texas, United States, 77583

United States, Utah

Metrodora Institute

West Valley City, Utah, United States, 84119

Sponsors and Collaborators

argenx

Iqvia Pty Ltd

More Information

• Responsible Party: argenx
• ClinicalTrials.gov Identifier: NCT05633407
• Other Study ID Numbers: ARGX-113-2104
• First Posted: December 1, 2022
• Last Update Posted: May 7, 2024
• Last Verified: May 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by argenx:

POTS; Long COVID; Postural Orthostatic Tachycardia Syndrome; efgartigimod

Additional relevant MeSH terms:

Postural Orthostatic Tachycardia Syndrome; Tachycardia; Syndrome; Disease; Pathologic Processes; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Cardiac Conduction System Disease; Orthostatic Intolerance; Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases