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

NCT05633407 | Completed Phase 2 Results FDA Drug

• 1 other identifier: ARGX-113-2104
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 11

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).

Conditions

Postural Orthostatic Tachycardia Syndrome

Keywords

POTS; Long COVID; Postural Orthostatic Tachycardia Syndrome; efgartigimod

Outcome Measures

Primary Outcomes (3)

• Change From Baseline to Week 24 in the COMPASS 31 (2-week Recall Version)

  Composite Autonomic Symptom Score (COMPASS) 31 modified version (2-week recall) is a self-rated questionnaire to evaluate the severity and distribution of autonomic symptoms in various autonomic nerve disorders. It consists of 31 questions in 6 weighted domains (orthostatic intolerance, vasomotor, secretomotor, gastrointestinal {GI}-mixed upper and diarrhea, bladder, and pupillomotor). A weighted total score of 0 (mild) to 100 (severe) was determined by adding a maximum raw score for each domain. Higher scores indicated a more severe degree of autonomic symptoms.

  Baseline (Day 1) and Week 24

• Change From Baseline to Week 24 in the MaPS

  The Malmö POTS Symptom Score (MaPS) score is a dedicated POTS symptom scoring questionnaire. The score consists of 12 questions that assess symptom burden related (tachycardia, palpitations, dizziness, presyncope) and unrelated to orthostatic intolerance (GI symptoms, insomnia, concentration difficulties). Participants graded their symptoms for the past 7 days using a visual analog scale ranging from 0 (no symptoms) to 10 (worst possible). The total score was calculated by summing up the items/individual items and range was 0 to 120 points, with higher scores indicating more severe symptoms.

  Baseline (Day 1) and Week 24

• Number of Participants With TEAEs and TESAEs

  An adverse event (AE) was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study drug, whether or not considered related to the study drug. A serious adverse event (SAE) was any untoward medical occurrence that at any dose resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or any other medically important event. Treatment-emergent adverse events (TEAEs) were defined as AEs with onset on or after the first administration of study drug up to and including 60 days after the last study drug administration.

  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 (7)

• Percentage of Participants With Improved PGI-S at Week 24

  Baseline (Day 1) and Week 24

• Percentage of Participants With Improved in PGI-C at Week 24

  Baseline (Day 1) and Week 24

• Change From Baseline to Week 24 in the PROMIS Fatigue Short Form 8a

  Baseline (Day 1) and Week 24

• Change From Baseline to Week 24 in the PROMIS Cognitive Function Short Form 6a

  Baseline (Day 1) and Week 24

• Percent Change From Baseline in Total IgG Levels at Week 24

  Baseline (Day 1) and Week 24

Study Arms (2)

Efgartigimod

EXPERIMENTAL

Receive efgartigimod IV 10mg/kg during weekly infusions during a treatment period of 24 weeks

Drug: Efgartigimod

Placebo

PLACEBO COMPARATOR

Receive a matching placebo during weekly infusions during a treatment period of 24 weeks

Drug: Placebo

Interventions

Efgartigimod DRUG

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

Efgartigimod

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Reached the age of consent when signing the informed consent form
• Capable of providing signed informed consent and complying with protocol requirements
• Diagnosed with new-onset POTS post-COVID-19 established by the following:
• 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
• 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)
• 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
• COMPASS 31 ≥35 at screening
• 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.
• Body mass index (BMI) \<35 kg/m2

You may not qualify if:

• 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
• 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
• 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
• Known HIV disease or common variable immunodeficiency
• 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:
• Basal cell or squamous cell skin cancer
• Carcinoma in situ of the cervix
• Carcinoma in situ of the breast
• Incidental 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 screening
• Positive 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 test
• Hepatitis C virus (HCV) based on HCV antibody assay unless a negative RNA test is available
• HIV
• A medical condition that could confound the results of the study or put the participant at undue risk in the investigator's judgment

Sponsors & Collaborators

• argenx: lead
• Iqvia Pty Ltd: collaborator

Study Sites (11)

University of California, San Diego Sulpizio Cardiovascular Center

La Jolla, California, 92037, United States

Location

Stanford Movement Disorder Center

Palo Alto, California, 94304, United States

Location

Northshore University Health System

Glenview, Illinois, 60026, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21224, United States

Location

Harvard Medical School, Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

Vandetbilt University Medical Center / Clinical Research Center

Nashville, Tennessee, 37232, United States

Location

Apex Trials Croup, LLC

Fort Worth, Texas, 76132, United States

Location

Texas Institute of Cardiology

McKinney, Texas, 75071, United States

Location

Pioneer Clinical Research

Rosharon, Texas, 77583, United States

Location

Metrodora Institute

West Valley City, Utah, 84119, United States

Location

Related Publications (1)

• Dani M, Fedorowski A. Tackling POTS Needs More Than Just a Sympathetic Approach. Hypertension. 2024 Nov;81(11):2248-2250. doi: 10.1161/HYPERTENSIONAHA.124.23716. Epub 2024 Oct 16. No abstract available.

  PMID: 39413203 DERIVED

MeSH Terms

Conditions

Postural Orthostatic Tachycardia Syndrome; Post-Acute COVID-19 Syndrome

Interventions

efgartigimod alfa

Condition Hierarchy (Ancestors)

Orthostatic Intolerance; Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Regulatory Manager
• Organization: argenx BV

regulatory@argenx.com

+32 93103400

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2022
• First Posted: December 1, 2022
• Study Start: September 23, 2022
• Primary Completion: April 18, 2024
• Study Completion: April 18, 2024
• Last Updated: May 23, 2025
• Results First Posted: May 23, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (11)