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

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.

Time frame: From the first dose of study drug (Day 1) up to 60 days post last dose of study drug, up to 383 days

Population: The safety analysis set (SAF) included all enrolled participants exposed to study drug.

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.

Time frame: Baseline (Day 1) and Weeks 24 and 48

Population: The FAS included all enrolled participants. Only those participants with data collected at Baseline, Weeks 24 and 48 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 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.

Time frame: Baseline (Day 1) and Weeks 24 and 48

Population: The FAS included all enrolled participants. Only those participants with data collected at Baseline, Weeks 24 and 48 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.

Time frame: Baseline (Day 1) and Weeks 24 and 48

Population: The FAS included all enrolled participants. Only those participants with data collected at Baseline, Weeks 24 and 48 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.

Time frame: Baseline (Day 1) and Weeks 24 and 48

Population: The FAS included all enrolled participants. Only those participants with data collected at Baseline, Weeks 24 and 48 are reported.

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.

Time frame: From the first dose of study drug (Day 1) up to Week 48

Population: The SAF included all enrolled participants exposed to study drug.

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.

Time frame: Baseline (Day 1) and Weeks 24 and 48

Population: The FAS included all enrolled participants. Only those participants with data collected at Baseline, Weeks 24 and 48 are reported.

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.

Time frame: Baseline (Day 1) and Weeks 24 and 48

Population: The FAS included all enrolled participants. Only those participants with data collected at Baseline, Weeks 24 and 48 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.

Time frame: Baseline (Day 1) and Weeks 24 and 48

Population: The SAF included all enrolled participants exposed to study drug. Only those participants with data collected at Baseline, Weeks 24 and 48 are reported.

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

Time frame: Pre-dose at Baseline (Day 1) and Weeks 1, 4, 12 and 24

Population: The pharmacokinetic analysis set (PKAS) included all enrolled 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.