Post-COVID Postural Orthostatic Tachycardia Syndrome
Conditions
Keywords
POTS
Brief summary
This is a prospective, phase 3, multicenter, double-blind, randomized placebo-controlled study to investigate the efficacy, safety, and pharmacokinetics (PK) of repeat doses of IgPro20 in participants with post SARS-CoV-2 infection 2019 postural orthostatic tachycardia syndrome (post-Coronavirus Disease 2019 \[COVID-19\] POTS \[post-COVID-POTS\]).
Interventions
BIOLOGICALIgPro20
IgPro20 is a 20% ready-to-use liquid formulation of polyvalent human immunoglobulin G (IgG) for subcutaneous (SC) administration
BIOLOGICALPlacebo
2% human albumin solution administered subcutaneously as a volume-matched dose to the experimental IMP.
Sponsors
CSL Behring
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Period 1 (double-blind): Participant, Care Provider, Investigator, Outcomes Assessor Period 2 (open-label): No masking
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Provide written informed consent and be willing and, in the opinion of the investigator, able to adhere to all protocol requirements. 2. Males and females aged ≥ 18 at the time of providing written informed consent. 3. Diagnosis of post-COVID POTS, defined by both a preceding COVID-19 infection based on confirmed historical documentation and onset of POTS symptoms developing within 4 months after COVID-19 infection as defined per consensus criteria. 4. COMPASS-31 score of at least 40 at the Screening visit. 5. Positive confirmatory standardized standing test (ie, HR increase of ≥ 30 bpm \[≥ 40 bpm for participants aged 18 to 19 years\] within 10 minutes in the absence of orthostatic hypotension) at the Screening visit.
Exclusion criteria
1. Treatment with Immunoglobulin G (IgG) or plasmapheresis within 12 weeks before Screening 2. Symptoms and / or diagnosis of or receiving treatment for POTS before COVID-19 infection 3. Prior diagnosis of or receiving current treatment at Screening for the following conditions (unless onset was related to the inciting POTS-associated COVID-19 infection): certain neurologic, autoimmune, endocrine, cardiac, or other disorders, and pre-existing psychiatric disorders 4. Presence of active infections, including human immunodeficiency virus infection, hepatitis B, hepatitis C, active SARS-CoV-2 infection, or any uncontrolled systemic infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants No Longer Meeting Diagnostic Criteria of Post-COVID POTS as Measured by Standardized Standing Test (ie, No Longer Experiencing HR Increase of ≥30 Bpm, in the Absence of 20 mmHg Decrease of SBP [Orthostatic Hypotension]) | At Baseline and at Week 25 | The reported data reflect the percentage of participants who no longer met the diagnostic criteria for Post-Coronavirus Disease 2019 (COVID) Postural Orthostatic Tachycardia Syndrome (POTS), as assessed by a standardized standing test (i.e., no longer experiencing a heart-rate (HR) increase of \>=30 bpm in the absence of a 20 mmHg decrease in systolic blood pressure \[SBP; orthostatic hypotension\]), among participants evaluated at that visit. The Baseline data represent the proportion of participants who were meeting the diagnostic criteria for post-COVID POTS. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Orthostatic Intolerance (OI) Score of Composite Autonomic Symptom Score 31 (COMPASS-31) | At Baseline and at Week 25 | The COMPASS-31 was a self-reported questionnaire that measures autonomic symptoms across six domains: OI, vasomotor, secretomotor, gastrointestinal (GI), bladder, and pupillomotor. The OI domain assesses symptoms including faintness, dizziness, feeling "goofy," or had difficulty thinking soon after standing up from a sitting or lying position, and generates a total score ranging from 0 to 40 with higher scores representing a higher symptom burden. The treatment effect of interest was the difference from baseline in OI score of COMPASS-31. A more negative change from baseline indicates a greater improvement in OI symptoms. |
| Change From Baseline in COMPASS-31 Total Score | At Baseline and at Week 25 | The COMPASS-31 was a self-reported questionnaire that measured autonomic symptoms related to six domains: OI, vasomotor, secretomotor, gastrointestinal (GI), bladder, and pupillomotor. This questionnaire generated a weighted score ranging from 0 to 100, with higher scores representing a higher symptom burden. A COMPASS-31 score of \>=40 indicated that participants had severe autonomic dysfunction. A more negative change from baseline indicates a greater improvement in autonomic symptoms. |
| Change From Baseline in Heart Rate Increase Within 10 Minutes of Standing Test | At Baseline and at Week 25 | Heart rate for the standing test was measured at the end of 10 minutes in the supine position and at 1, 3, 5, 7, and 10 minutes of standing. The change in heart rate during the standing test was calculated as the difference between the average of the two highest heart rate measurements (bpm) within 10 minutes of standing and the heart rate measurement (bpm) at the end of 10 minutes in the supine position. |
| Number of Participants With Treatment-Emergent Adverse Event (TEAE), Related TEAE, Serious TEAE and Related Serious TEAE | Up to Week 45 | — |
| Percentage of Participants With TEAE, Related TEAE, Serious TEAE and Related Serious TEAE | Up to Week 45 | The participant data were rounded to one decimal place. |
| Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities | Up to Week 45 | — |
| Percentage of Participants With Clinically Significant ECG Abnormalities | Up to Week 45 | — |
| Number of Participants With Change From Baseline in Clinically Significant ECG Abnormalities | From Baseline up to Week 45 | — |
| Percentage of Participants With Change From Baseline in Clinically Significant ECG Abnormalities | From Baseline up to Week 45 | — |
Countries
Canada, United States
Contacts
STUDY_DIRECTORStudy Director
CSL Behring
Participant flow
Recruitment details
This study was conducted in the United States.
Pre-assignment details
A total of 66 participants were screened, and 50 of these were screen failures. A total of 16 participants were randomized in the study.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants |
| Age, Continuous | 31.2 Years STANDARD_DEVIATION 8.78 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 5 | 0 / 3 |
| other Total, other adverse events | 10 / 11 | 4 / 5 | 0 / 3 |
| serious Total, serious adverse events | 0 / 11 | 0 / 5 | 0 / 3 |
Outcome results
None listed