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).
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). Efgartigimod may be a viable treatment option for individuals diagnosed with post-COVID-19 POTS because it has been shown to reduce IgG levels, including IgG autoantibodies, which may underlie some of the autonomic disease manifestations in these patients.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
53
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
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
University of California, San Diego Sulpizio Cardiovascular Center
La Jolla, California, United States
Stanford Movement Disorder Center
Palo Alto, California, United States
Northshore University Health System
Glenview, Illinois, United States
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.
Time frame: 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.
Time frame: 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.
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
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Johns Hopkins University
Baltimore, Maryland, United States
Harvard Medical School, Brigham and Women's Hospital
Boston, Massachusetts, United States
Case Western Reserve University
Cleveland, Ohio, United States
Vandetbilt University Medical Center / Clinical Research Center
Nashville, Tennessee, United States
Apex Trials Croup, LLC
Fort Worth, Texas, United States
Texas Institute of Cardiology
McKinney, Texas, United States
Pioneer Clinical Research
Rosharon, Texas, United States
...and 1 more locations
Percentage of Participants With Improved PGI-S at 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.
Time frame: Baseline (Day 1) and Week 24
Percentage of Participants With Improved in PGI-C at 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.
Time frame: Baseline (Day 1) and Week 24
Change From Baseline to Week 24 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.
Time frame: Baseline (Day 1) and Week 24
Change From Baseline to Week 24 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.
Time frame: Baseline (Day 1) and Week 24
Percent Change From Baseline in Total IgG Levels at 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.
Time frame: Baseline (Day 1) and Week 24
Serum Concentration of Efgartigimod
Serum samples were collected at specified timepoints to determine the concentration of efgartigimod.
Time frame: Pre-dose and post-dose at Baseline (Day 1), Weeks 1, 4, 12 and at Week 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.
Time frame: Up to Week 24