Open Label Extension of Efgartigimod in Adults With Post-COVID-19 POTS (POTS)

Open-Label Extension Study to Evaluate the Long-term Safety and Efficacy of Efgartigimod in Adult Patients With Post-COVID-19 Postural Orthostatic Tachycardia Syndrome (PC-POTS) Who Completed Study ARGX-113-2104

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

Study Overview

• Status: Terminated
• Conditions: Post-COVID Postural Orthostatic Tachycardia Syndrome Postural Orthostatic Tachycardia Syndrome
• Intervention / Treatment: Drug: Efgartigimod

Detailed Description

Study ARGX-113-2105 is a long-term, single-arm, open-label, multicenter extension of the ARGX-113-2104 study, designed to evaluate the long-term safety of efgartigimod IV in adult patients with PC-POTS. Participants will be enrolled from both active and placebo arms of the ARGX-113-2104 study and will receive efgartigimod IV 10 mg/kg in the extension study without knowledge of their prior treatment arm. To be eligible to enroll in this study, participants must have completed the 24-week treatment period of the ARGX-113-2104 study and must not have permanently discontinued the IMP in that study.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92037
      • UC Sand Diego Sulpizio Cardiovascular Center
    • Palo Alto, California, United States, 94304
      • Standford Movement Disorder Center
  • Illinois
    • Glenview, Illinois, United States, 60026
      • North Shore University HealthSystem
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals, Neurology Clinical Trials
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Apex Trials Group
    • Rosharon, Texas, United States, 77583
      • Pioneer Clinical Research
  • Utah
    • West Valley City, Utah, United States, 84119
      • Metrodora Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. The participant has completed the ARGX-113-2104 study without permanent discontinuation of IMP and agrees to directly roll over into the extension study without discontinuation of IMP.
2. The participant signs the informed consent form, and can comply with OLE study (ARGX-113-2105) protocol requirements.
3. The participant agrees to use contraceptives consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Contraceptive requirements are provided.
4. Female participants of childbearing potential must have a negative urine pregnancy test at baseline before receiving IMP.

Exclusion Criteria:

1. The participant has a clinically significant condition, based on the judgement of the Study Investigator, eg, laboratory abnormalities, 12-lead ECG readings, concomitant medical disease(s), etc., which may place them at undue risk or confound interpretation of study data.
2. The participant intends to become pregnant or start breastfeeding during the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Efgartigimod; Receive efgartigimod IV 10mg/kg infusions during a treatment period of 48 weeks	Drug: Efgartigimod; Participants will receive efgartigimod IV 10 mg/kg open label, respectively.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With TEAEs, TESAEs and TEAESIs	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. An adverse event of special interest (AESI) was an AE of scientific and medical concern specific to the sponsor's product or program. 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 383 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Weeks 24 and 48 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 Weeks 24 and 48
Change From Baseline to Weeks 24 and 48 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 numerical rating scale ranging from 0 (no symptoms) to 10 (very pronounced symptoms). 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 Weeks 24 and 48
Percentage of Participants With Improved PGI-S at Weeks 24 and 48	The Patient Global Impression-Severity (PGI-S) is a participant-rated, single-item scale to assess the severity of a health condition. The scale was used to assess the severity of symptoms over the past week (1-week recall) and overall experience of symptoms over the past 2 weeks (2-week recall). Both were rated on a 4-point type Likert scale, with scores ranging from 1 (none), 2 (mild), 3 (moderate), and 4 (severe). Higher scores indicate greater symptom severity. An "improved PGI-S" was defined by a change from baseline of -3, -2 and -1.	Baseline (Day 1) and Weeks 24 and 48
Percentage of Participants With Improved PGI-C at Weeks 24 and 48	The Patient Global Impression-Change (PGIC) is a single-item scale to capture the participant's perception of an overall change in their symptoms from start of study drug. It was rated on a 7-point Likert scale, with scores ranging from 1 (much better), 2 (somewhat better), 3 (a little better), 4 (no change), 5 (a little worse), 6 (somewhat worse), and 7 (much worse). Higher PGI-C scores signify worse outcome. An "improved PGI-C" was defined by a change from baseline of 1, 2 and 3.	Baseline (Day 1) and Weeks 24 and 48
Change From Baseline to Weeks 24 and 48 in the PROMIS Fatigue Short Form 8a	The Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form 8a assesses the impact and perceived fatigue during the last 7 days. This validated 8-question scale has 5 response options, with scores ranging from 1 (not at all) to 5 (very much). Total scores ranged from 8 to 40; higher scores indicated higher fatigue levels and were converted to a T-score with a mean of 50 and standard deviation of 10. A decrease in T-score (negative change from baseline) indicated improvement in fatigue.	Baseline (Day 1) and Weeks 24 and 48
Change From Baseline to Weeks 24 and 48 in the PROMIS Cognitive Function Short Form 6a	PROMIS Cognitive Function Short Form 6a assesses the frequency of cognitive difficulties experienced in the past 7 days. The questionnaire comprises 6 questions on subjective cognitive difficulties regarding a participant's concentration, memory, language, mental acuity, and perceived changes in cognitive functioning. The participant marks their response on a 5-point Likert scale (1: never and 5: very often). Scores ranged from 6 to 30; higher scores indicated worse perceived cognitive functioning and were converted to a T-score with a mean of 50 and standard deviation of 10. An increase in T-score (positive change from baseline) indicated better cognitive function.	Baseline (Day 1) and Weeks 24 and 48
Percent Change From Baseline in Total IgG Levels at Weeks 24 and 48	Blood samples for immunoglobulin G (IgG) analysis were collected at specified time points. Total IgG concentrations were quantified using validated methods at a central laboratory.	Baseline (Day 1) and Weeks 24 and 48
Serum Concentration of Efgartigimod	Serum samples were collected at specified timepoints to determine the concentration of efgartigimod.	Pre-dose at Baseline (Day 1) and Weeks 1, 4, 12 and 24
Number of Participants With ADAs Against Efgartigimod	Blood samples were collected at specified timepoints to assess anti-drug antibodies (ADAs) against efgartigimod. ADA incidence reported here was defined as total number of participants with treatment-induced and treatment-boosted ADA. Treatment-induced ADA was defined as a baseline negative sample and at least 1 positive post-baseline sample. Treatment-boosted ADA was defined as a baseline positive sample and the titer value increased 4-fold or more compared to baseline.	From the first dose of study drug (Day 1) up to Week 48

Collaborators and Investigators

• Sponsor: argenx
• Collaborators: IQVIA Pty Ltd

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2023
• Primary Completion (Actual): August 15, 2024
• Study Completion (Actual): August 15, 2024

Study Registration Dates

• First Submitted: June 22, 2023
• First Submitted That Met QC Criteria: June 22, 2023
• First Posted (Actual): June 26, 2023

Study Record Updates

• Last Update Posted (Estimated): October 23, 2025
• Last Update Submitted That Met QC Criteria: October 8, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Tachycardia Post-COVID; Postural Orthostatic Tachycardia Syndrome efgartigimod
• Additional Relevant MeSH Terms: Cardiac Conduction System Disease; Nervous System Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Disease; Arrhythmias, Cardiac; Primary Dysautonomias; Autonomic Nervous System Diseases; Orthostatic Intolerance; Syndrome; Tachycardia; Postural Orthostatic Tachycardia Syndrome; efgartigimod alfa
• Other Study ID Numbers: ARGX-113-2105

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No