Trial Outcomes & Findings for Efficacy and Safety Study of Efgartigimod in Adults With Post-COVID-19 POTS (NCT NCT05633407)

Last Updated: 2025-05-23

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

53 participants

Primary outcome timeframe

Baseline (Day 1) and Week 24

Results posted on

2025-05-23

Participant Flow

This phase 2, randomized, double-blind study was conducted at 11 sites in the United States from 23-Sep-22 to 18-Apr-24 in participants with post-coronavirus disease 2019 (COVID-19) postural orthostatic tachycardia syndrome (POTS).

The study consisted of a screening period (approximately 4 weeks), a treatment period (24 weeks) and a follow-up period (approximately 8 weeks for participants who did not roll over to the open label extension study ARGX-113-2105 \[NCT05918978). A total of 53 participants were randomized in a 2:1 ratio to receive either efgartigimod or matching placebo, respectively.

Participant milestones

Participant milestones
Measure	Efgartigimod Participants received efgartigimod 10 milligram/kilogram (mg/kg) via intravenous (IV) infusion once weekly from Day 1 up to 24 weeks.	Placebo Participants received placebo matched to efgartigimod via IV infusion once weekly from Day 1 up to 24 weeks.
Overall Study STARTED	36	17
Overall Study COMPLETED	31	16
Overall Study NOT COMPLETED	5	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Efgartigimod Participants received efgartigimod 10 milligram/kilogram (mg/kg) via intravenous (IV) infusion once weekly from Day 1 up to 24 weeks.	Placebo Participants received placebo matched to efgartigimod via IV infusion once weekly from Day 1 up to 24 weeks.
Overall Study Physician Decision	2	0
Overall Study Adverse Event	1	0
Overall Study Withdrawal by Subject	1	0
Overall Study Other	1	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Efgartigimod n=36 Participants Participants received efgartigimod 10 mg/kg via IV infusion once weekly from Day 1 up to 24 weeks.	Placebo n=17 Participants Participants received placebo matched to efgartigimod via IV infusion once weekly from Day 1 up to 24 weeks.	Total n=53 Participants Total of all reporting groups
Age, Continuous	38.4 years STANDARD_DEVIATION 12.82 • n=5 Participants	36.8 years STANDARD_DEVIATION 11.99 • n=7 Participants	37.9 years STANDARD_DEVIATION 12.47 • n=5 Participants
Sex: Female, Male Female	30 Participants n=5 Participants	15 Participants n=7 Participants	45 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	33 Participants n=5 Participants	13 Participants n=7 Participants	46 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	33 Participants n=5 Participants	17 Participants n=7 Participants	50 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) and Week 24

Population: The FAS included all randomized participants who received at least 1 dose of study drug. Only those participants with data collected at Baseline and Week 24 are reported.

Outcome measures

Outcome measures
Measure	Efgartigimod n=22 Participants Participants received efgartigimod 10 mg/kg via IV infusion once weekly from Day 1 up to 24 weeks.	Placebo n=15 Participants Participants received placebo matched to efgartigimod via IV infusion once weekly from Day 1 up to 24 weeks.
Change From Baseline to Week 24 in the COMPASS 31 (2-week Recall Version)	-14.369 score on a scale Standard Deviation 15.2541	-15.957 score on a scale Standard Deviation 17.2963

PRIMARY outcome

Timeframe: Baseline (Day 1) and Week 24

Population: The FAS included all randomized participants who received at least 1 dose of study drug. Only those participants with data collected at Baseline and Week 24 are reported.

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.

Outcome measures

Outcome measures
Measure	Efgartigimod n=22 Participants Participants received efgartigimod 10 mg/kg via IV infusion once weekly from Day 1 up to 24 weeks.	Placebo n=15 Participants Participants received placebo matched to efgartigimod via IV infusion once weekly from Day 1 up to 24 weeks.
Change From Baseline to Week 24 in the MaPS	-23.5 score on a scale Standard Deviation 25.87	-19.8 score on a scale Standard Deviation 27.75

PRIMARY outcome

Timeframe: From the first dose of study drug (Day 1) up to 60 days post last dose of study drug, up to 236 days

Population: The safety analysis set (SAF) included all randomized participants who received at least 1 dose of study drug.

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.

Outcome measures

Outcome measures
Measure	Efgartigimod n=36 Participants Participants received efgartigimod 10 mg/kg via IV infusion once weekly from Day 1 up to 24 weeks.	Placebo n=17 Participants Participants received placebo matched to efgartigimod via IV infusion once weekly from Day 1 up to 24 weeks.
Number of Participants With TEAEs and TESAEs TEAEs	31 Participants	14 Participants
Number of Participants With TEAEs and TESAEs TESAEs	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 24

Population: The FAS included all randomized participants who received at least 1 dose of study drug. Only participants with available data at week 24 are included.

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.

Outcome measures

Outcome measures
Measure	Efgartigimod n=22 Participants Participants received efgartigimod 10 mg/kg via IV infusion once weekly from Day 1 up to 24 weeks.	Placebo n=15 Participants Participants received placebo matched to efgartigimod via IV infusion once weekly from Day 1 up to 24 weeks.
Percentage of Participants With Improved PGI-S at Week 24 1-week recall	45.5 percentage of participants	53.3 percentage of participants
Percentage of Participants With Improved PGI-S at Week 24 2-week recall	54.5 percentage of participants	33.3 percentage of participants

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 24

Population: The FAS included all randomized participants who received at least 1 dose of study drug. Only participants with data available for week 24 are included.

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.

Outcome measures

Outcome measures
Measure	Efgartigimod n=26 Participants Participants received efgartigimod 10 mg/kg via IV infusion once weekly from Day 1 up to 24 weeks.	Placebo n=15 Participants Participants received placebo matched to efgartigimod via IV infusion once weekly from Day 1 up to 24 weeks.
Percentage of Participants With Improved in PGI-C at Week 24	65.4 percentage of participants	53.3 percentage of participants

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 24

Population: The FAS included all randomized participants who received at least 1 dose of study drug. Only those participants with data collected at Baseline and Week 24 are reported.

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.

Outcome measures

Outcome measures
Measure	Efgartigimod n=22 Participants Participants received efgartigimod 10 mg/kg via IV infusion once weekly from Day 1 up to 24 weeks.	Placebo n=15 Participants Participants received placebo matched to efgartigimod via IV infusion once weekly from Day 1 up to 24 weeks.
Change From Baseline to Week 24 in the PROMIS Fatigue Short Form 8a	-9.5 T-score Standard Deviation 8.77	-7.0 T-score Standard Deviation 9.40

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 24

Population: The FAS included all randomized participants who received at least 1 dose of study drug. Only those participants with data collected at Baseline and Week 24 are reported.

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.

Outcome measures

Outcome measures
Measure	Efgartigimod n=22 Participants Participants received efgartigimod 10 mg/kg via IV infusion once weekly from Day 1 up to 24 weeks.	Placebo n=15 Participants Participants received placebo matched to efgartigimod via IV infusion once weekly from Day 1 up to 24 weeks.
Change From Baseline to Week 24 in the PROMIS Cognitive Function Short Form 6a	3.9 T-score Standard Deviation 9.58	6.7 T-score Standard Deviation 9.74

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 24

Population: The SAF included all randomized participants who received at least 1 dose of study drug. Only those participants with data collected at Baseline and Week 24 are reported.

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.

Outcome measures

Outcome measures
Measure	Efgartigimod n=27 Participants Participants received efgartigimod 10 mg/kg via IV infusion once weekly from Day 1 up to 24 weeks.	Placebo n=14 Participants Participants received placebo matched to efgartigimod via IV infusion once weekly from Day 1 up to 24 weeks.
Percent Change From Baseline in Total IgG Levels at Week 24	-69.341 percent change Standard Deviation 6.0637	5.868 percent change Standard Deviation 13.1379

SECONDARY outcome

Timeframe: Pre-dose and post-dose at Baseline (Day 1), Weeks 1, 4, 12 and at Week 24

Population: The pharmacokinetic (PK) analysis set included all randomized participants who received at least 1 dose of efgartigimod and had at least 1 measured concentration of efgartigimod at a scheduled PK time point after start of dosing without protocol violations or events with potential to affect the PK concentration. Only those participants with data collected at specified timepoints are reported.

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

Outcome measures

Outcome measures
Measure	Efgartigimod n=34 Participants Participants received efgartigimod 10 mg/kg via IV infusion once weekly from Day 1 up to 24 weeks.	Placebo Participants received placebo matched to efgartigimod via IV infusion once weekly from Day 1 up to 24 weeks.
Serum Concentration of Efgartigimod Week 24	10450 nanogram (ng)/mL Standard Deviation 3894	—
Serum Concentration of Efgartigimod Baseline, pre-dose	NA nanogram (ng)/mL Standard Deviation NA NA indicates that the mean and standard deviation were below the lower limit of quantification (LLOQ). LLOQ was 200 ng/mL.	—
Serum Concentration of Efgartigimod Baseline, post-dose	260536 nanogram (ng)/mL Standard Deviation 235110	—
Serum Concentration of Efgartigimod Week 1, pre-dose	10711 nanogram (ng)/mL Standard Deviation 3580	—
Serum Concentration of Efgartigimod Week 1, post-dose	235100 nanogram (ng)/mL Standard Deviation 68316	—
Serum Concentration of Efgartigimod Week 4, pre-dose	12612 nanogram (ng)/mL Standard Deviation 5631	—
Serum Concentration of Efgartigimod Week 4, post-dose	230308 nanogram (ng)/mL Standard Deviation 54329	—
Serum Concentration of Efgartigimod Week 12, pre-dose	18966 nanogram (ng)/mL Standard Deviation 39993	—
Serum Concentration of Efgartigimod Week 12, post-dose	216760 nanogram (ng)/mL Standard Deviation 56621	—

SECONDARY outcome

Timeframe: Up to Week 24

Population: The SAF included all randomized participants who received at least 1 dose of study drug.

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.

Outcome measures

Outcome measures
Measure	Efgartigimod n=36 Participants Participants received efgartigimod 10 mg/kg via IV infusion once weekly from Day 1 up to 24 weeks.	Placebo n=17 Participants Participants received placebo matched to efgartigimod via IV infusion once weekly from Day 1 up to 24 weeks.
Number of Participants With ADAs Against Efgartigimod	5 Participants	1 Participants

Adverse Events

Efgartigimod

Serious events: 0 serious events

Other events: 31 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Regulatory Manager

argenx BV

Phone: +32 93103400

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER