NCT05633407: POTS

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

Completed Phase 2 Results posted Last updated 23 May 2025

What this trial tests

Phase 2 trial testing Efgartigimod in Postural Orthostatic Tachycardia Syndrome in 53 participants. Completed in 18 April 2024.

Timeline

23 September 2022

Primary endpoint
18 April 2024

18 April 2024

Quick facts

Lead sponsor	argenx
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	53
Start date	23 September 2022
Primary completion	18 April 2024
Estimated completion	18 April 2024
Sites	11 locations across United States

Drugs / interventions tested

• Efgartigimod — full drug profile →
• Placebo

Conditions studied

• Postural Orthostatic Tachycardia Syndrome — all drugs for Postural Orthostatic Tachycardia Syndrome →

Sponsor

argenx — full company profile →

Who can join

18 and older, any sex, with Postural Orthostatic Tachycardia Syndrome. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline to Week 24 in the COMPASS 31 (2-week Recall Version) Primary · Baseline (Day 1) and Week 24

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.

Group	Value	95% CI
Efgartigimod	-14.369	± 15.2541
Placebo	-15.957	± 17.2963

Change From Baseline to Week 24 in the MaPS Primary · Baseline (Day 1) and Week 24

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.

Group	Value	95% CI
Efgartigimod	-23.5	± 25.87
Placebo	-19.8	± 27.75

Number of Participants With TEAEs and TESAEs Primary · From the first dose of study drug (Day 1) up to 60 days post last dose of study drug, up to 236 days

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 w

TEAEs

Group	Value	95% CI
Efgartigimod	31
Placebo	14

TESAEs

Group	Value	95% CI
Efgartigimod	0
Placebo	0

Percentage of Participants With Improved PGI-S at Week 24 Secondary · Baseline (Day 1) and Week 24

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.

1-week recall

Group	Value	95% CI
Efgartigimod	45.5
Placebo	53.3

2-week recall

Group	Value	95% CI
Efgartigimod	54.5
Placebo	33.3

Percentage of Participants With Improved in PGI-C at Week 24 Secondary · Baseline (Day 1) and Week 24

The Patient Global Impression-Change (PGIC) is a single-item scale to capture the participant's perception of a change in their overall symptom severity. Overall change in symptoms 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.

Group	Value	95% CI
Efgartigimod	65.4
Placebo	53.3

Change From Baseline to Week 24 in the PROMIS Fatigue Short Form 8a Secondary · Baseline (Day 1) and Week 24

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.

Group	Value	95% CI
Efgartigimod	-9.5	± 8.77
Placebo	-7.0	± 9.40

Change From Baseline to Week 24 in the PROMIS Cognitive Function Short Form 6a Secondary · Baseline (Day 1) and Week 24

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-

Group	Value	95% CI
Efgartigimod	3.9	± 9.58
Placebo	6.7	± 9.74

Percent Change From Baseline in Total IgG Levels at Week 24 Secondary · Baseline (Day 1) and Week 24

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.

Group	Value	95% CI
Efgartigimod	-69.341	± 6.0637
Placebo	5.868	± 13.1379

Serum Concentration of Efgartigimod Secondary · Pre-dose and post-dose at Baseline (Day 1), Weeks 1, 4, 12 and at Week 24

Serum samples were collected at specified timepoints to determine the concentration of efgartigimod.

Baseline, pre-dose

Group	Value	95% CI
Efgartigimod	NA	± NA

Baseline, post-dose

Group	Value	95% CI
Efgartigimod	260536	± 235110

Week 1, pre-dose

Group	Value	95% CI
Efgartigimod	10711	± 3580

Week 1, post-dose

Group	Value	95% CI
Efgartigimod	235100	± 68316

Week 4, pre-dose

Group	Value	95% CI
Efgartigimod	12612	± 5631

Week 4, post-dose

Group	Value	95% CI
Efgartigimod	230308	± 54329

Week 12, pre-dose

Group	Value	95% CI
Efgartigimod	18966	± 39993

Week 12, post-dose

Group	Value	95% CI
Efgartigimod	216760	± 56621

Number of Participants With ADAs Against Efgartigimod Secondary · Up to Week 24

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.

Group	Value	95% CI
Efgartigimod	5
Placebo	1

Adverse events — posted to ClinicalTrials.gov

Time frame: From the first dose of study drug (Day 1) up to 60 days post last dose of study drug, up to 236 days.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Efgartigimod

Serious: 0/36 (0%)

Deaths: 0/36

Placebo

Serious: 0/17 (0%)

Deaths: 0/17

Other adverse events (77 terms — click to expand)

Reaction	System	Efgartigimod	Placebo
Fatigue	General disorders	—	—
Headache	Nervous system disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Urinary tract infection	Infections and infestations	—	—
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Pyrexia	General disorders	—	—
COVID-19	Infections and infestations	—	—
Contusion	Injury, poisoning and procedural complications	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—
Dizziness	Nervous system disorders	—	—
Insomnia	Psychiatric disorders	—	—
Nasal congestion	Respiratory, thoracic and mediastinal disorders	—	—
Tachycardia	Cardiac disorders	—	—
Abdominal discomfort	Gastrointestinal disorders	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Gastritis	Gastrointestinal disorders	—	—
Chills	General disorders	—	—
Infusion site bruising	General disorders	—	—
Infusion site pain	General disorders	—	—
Malaise	General disorders	—	—
Bronchitis	Infections and infestations	—	—
Infusion related reaction	Injury, poisoning and procedural complications	—	—
Blood glucose increased	Investigations	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—
Dysgeusia	Nervous system disorders	—	—
Migraine	Nervous system disorders	—	—
Pollakiuria	Renal and urinary disorders	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	—	—
Rash	Skin and subcutaneous tissue disorders	—	—
Palpitations	Cardiac disorders	—	—
Ear discomfort	Ear and labyrinth disorders	—	—
Ear pain	Ear and labyrinth disorders	—	—

Data from ClinicalTrials.gov NCT05633407 adverse events section.

Sponsor's own 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).

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

1. Fighting Post-COVID and ME/CFS - development of curative therapies.
   Scheibenbogen C, Bellmann-Strobl JT, Heindrich C, Wittke K, et al · · 2023 · cited 32× · PMID 37396922 · DOI 10.3389/fmed.2023.1194754
2. Efficacy of repeated immunoadsorption in patients with post-COVID myalgic encephalomyelitis/chronic fatigue syndrome and elevated β2-adrenergic receptor autoantibodies: a prospective cohort study.
   Stein E, Heindrich C, Wittke K, Kedor C, et al · · 2025 · cited 18× · PMID 39759581 · DOI 10.1016/j.lanepe.2024.101161
3. Dysautonomia following Lyme disease: a key component of post-treatment Lyme disease syndrome?
   Adler BL, Chung T, Rowe PC, Aucott J. · · 2024 · cited 15× · PMID 38390594 · DOI 10.3389/fneur.2024.1344862
4. Postural Orthostatic Tachycardia Syndrome in COVID-19: A Contemporary Review of Mechanisms, Clinical Course and Management.
   Narasimhan B, Calambur A, Moras E, Wu L, et al · · 2023 · cited 14× · PMID 37204997 · DOI 10.2147/vhrm.s380270
5. Targeting the Neonatal Fc Receptor in Autoimmune Diseases: Pipeline and Progress.
   Gjølberg TT, Mester S, Calamera G, Telstad JS, et al · · 2025 · cited 10× · PMID 40156757 · DOI 10.1007/s40259-025-00708-2