Double-blind, Randomized, Placebo-controlled Study Evaluating Efficacy and Safety of IgPro20 in Post-COVID-19 POTS

Double-blind, Randomized, Placebo-controlled Phase 3 Study Evaluating Efficacy and Safety of IgPro20 (Subcutaneous Immunoglobulin, HIZENTRA®) in Post-COVID-19 Postural Orthostatic Tachycardia Syndrome (POTS)

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]).

Study Overview

• Status: Terminated
• Conditions: Post-COVID Postural Orthostatic Tachycardia Syndrome
• Intervention / Treatment: Biological: IgPro20; Biological: Placebo

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Calgary, Canada, T2N 4Z6
    • Libin Cardiovascular Institute University of Calgary
  • Edmonton, Canada, T6G 2B7
    • University of Alberta Hospital
  • Québec, Canada, H4A 3J1
    • McGill University Health Centre
  • Sherbrooke, Canada, J1H 5N4
    • Ciussse-Chus
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-1152
      • University of Alabama Hospital at Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Center for Complex Neurology, EDS & POTS
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic Arizona
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Arkansas Cardiology Clinic - Little Rock
  • California
    • La Jolla, California, United States, 92037
      • UC San Diego Health
    • Orange, California, United States, 92868
      • University of California Irvine
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Health
  • Florida
    • Miami, Florida, United States, 33173
      • Well Pharma Medical Research, Corp
    • Miami, Florida, United States, 33166
      • Hope Research Network
  • Georgia
    • Savannah, Georgia, United States, 31406
      • Velocity Clinical Research, Savannah
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • LSU Health Sciences Center
    • New Orleans, Louisiana, United States, 70119
      • Velocity Clinical Research, Metairie
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins Bayview Medical Center PMR
  • Massachusetts
    • Belmont, Massachusetts, United States, 02478
      • Mass General Brigham (Massachusetts General Hospital)
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Profound Research LLC at Millennium Affiliated Physicians
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • Velocity Clinical Research - Lincoln
  • New York
    • Buffalo, New York, United States, 14221
      • Dysautonomia Clinic
    • Patchogue, New York, United States, 11772
      • NYU Langone Health South Shore Neurologic Associates
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45236
      • Bernstein Clinical Research Center
    • Cleveland, Ohio, United States, 44195
      • University Hospital Cleveland Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73134
      • Hightower Clinical
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Penn Presbyterian Medical Center
  • South Carolina
    • Union, South Carolina, United States, 29379
      • Velocity Clinical Research - Union
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Austin, Texas, United States, 78712
      • UT Austin Dell Medical School
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77054
      • Prolato Clinical Research Center
    • McKinney, Texas, United States, 75069
      • Sunbeam Clinical Research
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center
  • Utah
    • Salt Lake City, Utah, United States, 84102
      • Bateman Horne Center
    • West Valley City, Utah, United States, 84119
      • Metrodora Institute
  • Virginia
    • Hampton, Virginia, United States, 23666
      • Velocity Clinical Research - Hampton
    • Richmond, Virginia, United States, 23219
      • Vcu Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Biological: Placebo; 2% human albumin solution administered subcutaneously as a volume-matched dose to the experimental IMP.
Experimental: IgPro20	Biological: IgPro20; IgPro20 is a 20% ready-to-use liquid formulation of polyvalent human immunoglobulin G (IgG) for subcutaneous (SC) administration; Other Names: HIZENTRA®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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])	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.	At Baseline and at Week 25

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Orthostatic Intolerance (OI) Score of Composite Autonomic Symptom Score 31 (COMPASS-31)	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.	At Baseline and at Week 25
Change From Baseline in COMPASS-31 Total Score	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.	At Baseline and at Week 25
Change From Baseline in Heart Rate Increase Within 10 Minutes of Standing Test	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.	At Baseline and at Week 25
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	The participant data were rounded to one decimal place.	Up to Week 45
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

Collaborators and Investigators

• Sponsor: CSL Behring
• Investigators: Study Director: Study Director, CSL Behring

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2024
• Primary Completion (Actual): June 20, 2025
• Study Completion (Actual): July 11, 2025

Study Registration Dates

• First Submitted: July 26, 2024
• First Submitted That Met QC Criteria: July 26, 2024
• First Posted (Actual): July 29, 2024

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: March 24, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: POTS
• Additional Relevant MeSH Terms: Cardiac Conduction System Disease; Nervous System Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Disease; Arrhythmias, Cardiac; Primary Dysautonomias; Autonomic Nervous System Diseases; Orthostatic Intolerance; Syndrome; Tachycardia; Postural Orthostatic Tachycardia Syndrome; Hizentra
• Other Study ID Numbers: IgPro20_3010; 2023-508744-22-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: CSL will consider on a case-by-case basis requests to share Individual Patient Data (IPD) with external bona-fide, qualified scientific and medical researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at clinicaltrials@cslbehring.com.
• IPD Sharing Time Frame: Requests for IPD will generally be considered once review by major regulatory authorities (ie FDA, EMA) is complete and the primary publication is available.

IPD Sharing Access Criteria

Proposed research should seek to answer a previously unanswered important medical or scientific question.

Applicable country specific privacy and other laws and regulations will be considered and may prevent sharing of IPD.

If the request is approved and the researcher has executed an appropriate data sharing agreement, IPD that has been appropriately anonymized will be available.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No