IgPro20 for POTS

No longer recruiting at 41 trial locations

Overseen By Trial Registration Coordinator

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: CSL Behring

Must not be taking: Immunoglobulin G, Plasmapheresis

Disqualifiers: Neurologic, Autoimmune, Endocrine, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 25 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called IgPro20 (a subcutaneous immunoglobulin) to determine its effectiveness for people with post-COVID POTS, a condition where heart rate significantly increases upon standing after COVID-19. The study compares IgPro20 to a placebo to evaluate its effectiveness and safety. Individuals who developed POTS symptoms within four months of a confirmed COVID-19 infection may qualify for this trial. Participants must demonstrate a significant heart rate increase when standing during a test. As a Phase 3 trial, this study is the final step before FDA approval, offering participants the opportunity to contribute to the potential availability of a new treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are currently receiving treatment for certain conditions like neurologic, autoimmune, or cardiac disorders, you may not be eligible to participate.

Is there any evidence suggesting that IgPro20 is likely to be safe for humans?

Research has shown that IgPro20 has been studied for its safety in treating postural orthostatic tachycardia syndrome (POTS) after COVID-19. In previous studies, IgPro20 was generally well-tolerated, with most participants not experiencing severe side effects.

Although specific safety data from the current trial are not yet available, IgPro20's progression to this stage suggests it has demonstrated a reasonable level of safety in earlier research. Typically, treatments at this phase have already been tested in many people to assess serious side effects.

For those considering joining a trial for IgPro20, it is reassuring that studies so far support its safety in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for POTS?

Unlike the standard treatments for Postural Orthostatic Tachycardia Syndrome (POTS), which typically include beta-blockers, fludrocortisone, or midodrine to manage symptoms, IgPro20 offers a unique approach. IgPro20 is an immunoglobulin therapy that targets the immune system, potentially addressing an underlying cause of POTS rather than just alleviating the symptoms. Researchers are excited about IgPro20 because it may offer a new mechanism of action, providing relief for patients who don't respond well to existing medications. Additionally, IgPro20 is administered subcutaneously, which can be more convenient than intravenous options, making it easier for long-term management.

What evidence suggests that IgPro20 might be an effective treatment for post-COVID-POTS?

Research has shown that IgPro20, a treatment that boosts the immune system, may help people with POTS, especially those who developed it after a COVID-19 infection. In this trial, participants will receive either IgPro20 or a placebo. Studies have found that patients with severe POTS symptoms improved significantly after receiving similar treatments. These patients reported fewer issues with symptoms like dizziness and a rapid heartbeat when standing up. The treatment uses antibodies to help balance the immune system, which might explain its effectiveness for POTS. Although more research is ongoing, these findings suggest that IgPro20 could be a promising option for managing post-COVID POTS. ^{1 2 4 5 6}

Who Is on the Research Team?

Study Director

Principal Investigator

CSL Behring

Are You a Good Fit for This Trial?

This trial is for individuals who have developed Postural Orthostatic Tachycardia Syndrome (POTS) following a SARS-CoV-2 infection. Participants should be experiencing symptoms like rapid heartbeat when standing up.

Inclusion Criteria

Provide written informed consent and be willing and able to adhere to all protocol requirements

COMPASS-31 score of at least 40 at the Screening visit

I was diagnosed with POTS after having COVID-19.

Exclusion Criteria

I was diagnosed or treated for POTS before getting COVID-19.

I have not had IgG or plasmapheresis in the last 12 weeks.

I do not have any active infections like HIV, hepatitis B/C, COVID-19, or other uncontrolled infections.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive repeat doses of IgPro20 or placebo in a double-blind, randomized manner

25 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• IgPro20

Trial Overview The study is testing the effectiveness and safety of IgPro20, an immunoglobulin therapy, compared to a placebo in treating post-COVID-19 POTS. Patients are randomly assigned to receive either IgPro20 or a placebo without knowing which one they get.

How Is the Trial Designed?

Group I: IgPro20 Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

IgPro20 is already approved in European Union, United States, Canada, Japan, Switzerland for the following indications:

Approved in European Union as Hizentra for:

• Chronic inflammatory demyelinating polyneuropathy
• Primary immunodeficiency

Approved in United States as Hizentra for:

• Chronic inflammatory demyelinating polyneuropathy
• Primary immunodeficiency

Approved in Canada as Hizentra for:

• Chronic inflammatory demyelinating polyneuropathy
• Primary immunodeficiency

Approved in Japan as Hizentra for:

• Chronic inflammatory demyelinating polyneuropathy
• Primary immunodeficiency

Approved in Switzerland as Hizentra for:

• Chronic inflammatory demyelinating polyneuropathy
• Primary immunodeficiency

Who Is Running the Clinical Trial?

CSL Behring

Lead Sponsor

Trials

204

Recruited

1,207,000+

Dr. Paul McKenzie

CSL Behring

Chief Executive Officer since 2023

PhD in Chemical Engineering from Carnegie Mellon University, B.S. in Chemical Engineering from the University of Pennsylvania

Dr. Bill Mezzanotte

CSL Behring

Chief Medical Officer since 2021

MD from Duke University

Published Research Related to This Trial

The study validated a population pharmacokinetic (popPK) model for IgPro20 (Hizentra®), showing it accurately predicts serum IgG concentration profiles after biweekly administration in 173 patients, with a total of 4078 observations.

IgPro20 demonstrated a clearance rate of 0.138 L/day and a central compartment volume of 3.95 L, indicating effective dosing regimens for patients with primary immunodeficiencies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population pharmacokinetic analysis of weekly and biweekly IgPro20 (Hizentra®) dosing in patients with primary immunodeficiency. Zhang, Y., Baheti, G., Chapdelaine, H., et al.[2021]

In a Phase III study involving 24 Japanese patients with primary immunodeficiency, switching from intravenous immunoglobulin (IVIG) to subcutaneous immunoglobulin (IgPro20) significantly improved quality of life, with Life Quality Index scores increasing from 45.1 to 71.9, indicating a large effect size.

The transition to IgPro20 also led to a 60% reduction in productivity loss and increased the number of patients able to maintain work and household duties, highlighting the economic benefits and reduced hospital visits associated with this home-based treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-minimization analysis of IgPro20, a subcutaneous immunoglobulin, in Japanese patients with primary immunodeficiency. Igarashi, A., Kanegane, H., Kobayashi, M., et al.[2018]

In a study involving 41 patients with chronic inflammatory demyelinating polyneuropathy (CIDP), switching from intravenous immunoglobulin (IVIg) to an equivalent dose of subcutaneous immunoglobulin (IgPro20) maintained stability in clinical outcomes such as disability and muscle strength over 6 months.

A significant 88% of patients preferred the subcutaneous IgPro20 treatment over IVIg after the switch, indicating not only efficacy but also improved patient satisfaction with the new treatment method.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Switch from intravenous to subcutaneous immunoglobulin IgPro20 in CIDP patients: a prospective observational study under real-world conditions. Gingele, S., Koch, M., Saparilla, AC., et al.[2022]

Hizentra (IgPro20) is a new 20% liquid preparation of human IgG for subcutaneous administration that provides high and stable serum IgG levels, is well tolerated, and can be self-administered, making it convenient for patients.

Clinical use of Hizentra has been shown to effectively protect both adults and children with primary immunodeficiencies from serious bacterial infections, representing a significant advancement in immunoglobulin replacement therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous immunoglobulin replacement therapy with Hizentra, the first 20% SCIG preparation: a practical approach. Jolles, S., Sleasman, JW.[2011]

The HILO study demonstrated that subcutaneous IgPro20 (Hizentra®) can be safely administered at high infusion rates (up to 100 mL/h) in patients with primary immunodeficiency, with low rates of adverse events (0.216 per infusion).

Responder rates were high, with 86.7% of patients successfully completing their planned infusions in the Volume Cohort, indicating that pump-assisted infusions are effective and can lead to fewer injection sites and shorter infusion times.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Tolerability of Subcutaneous IgPro20 at High Infusion Parameters in Patients with Primary Immunodeficiency: Findings from the Pump-Assisted Administration Cohorts of the HILO Study. Anderson, JT., Bonagura, VR., Cowan, J., et al.[2022]

A phase III study involving 49 patients with primary immunodeficiency demonstrated that subcutaneous IgPro20 therapy effectively maintained serum IgG levels and provided protection against infections over 15 months, with a mean serum IgG level of 12.5 g/L.

The therapy was well-tolerated, with 99% of adverse events being mild or moderate, and no serious IgPro20-related adverse events or serious bacterial infections reported, indicating a favorable safety profile compared to traditional intravenous immunoglobulin therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of a new 20% immunoglobulin preparation for subcutaneous administration, IgPro20, in patients with primary immunodeficiency. Hagan, JB., Fasano, MB., Spector, S., et al.[2022]

In a pivotal phase III trial, maintenance therapy with subcutaneous immunoglobulin (IgPro20) for 24 weeks significantly reduced relapse rates in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) compared to placebo, demonstrating its efficacy as a treatment option.

IgPro20 was well tolerated with low rates of systemic adverse events, and over half of the patients preferred it over their previous intravenous immunoglobulin (IVIg) therapy, indicating it may be a more convenient and safer alternative for long-term management of CIDP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune Globulin Subcutaneous (Human) 20% (Hizentra®): A Review in Chronic Inflammatory Demyelinating Polyneuropathy. Lamb, YN., Syed, YY., Dhillon, S.[2022]

The study demonstrated that the pharmacokinetics of subcutaneous IgPro20 (Hizentra®) are equivalent to those of intravenous IgPro10 (Privigen®), with similar area under the serum concentration-time curves (AUCs), indicating effective immunoglobulin replacement therapy.

Eighteen patients participated in the trial, and the results showed that IgPro20 can be safely administered with a dose adjustment coefficient of 1.53, ensuring adequate protection against infections without the risk of under-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of subcutaneous IgPro20 in patients with primary immunodeficiency. Wasserman, RL., Melamed, I., Nelson, RP., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06524739

Study Details | NCT06524739 | Double-blind, Randomized, ... Sponsor decision, not for safety reasons. Double-blind, Randomized, Placebo-controlled Study Evaluating Efficacy and Safety of IgPro20 in Post-COVID-19 POTS.

2. reaganudall.org reaganudall.org/clinical-trial/double-blind-randomized-placebo-controlled-study-evaluating-efficacy-and-safety

Double-blind, Randomized, Placebo-controlled Study ... This is a prospective, phase 3, multicenter, double-blind, randomized placebo-controlledstudy to investigate the efficacy, safety, and pharmacokinetics.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36008726/

Immunotherapy with subcutaneous immunoglobulin or ... Patients with severe, treatment-refractory POTS experienced significant functional improvement with reduction in the autonomic symptoms following immunotherapy ...

4. frontiersin.org frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2025.1647203/full

Immunotherapies for postural orthostatic tachycardia ... Double-blind, randomized, placebo-controlled phase 3 study evaluating efficacy and safety of igPro20 (Subcutaneous immunoglobulin, HIZENTRA®) in post-COVID-19 ...

5. covid.trialstoday.org covid.trialstoday.org/trial/NCT06524739

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

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11562304/

Postural orthostatic tachycardia syndrome after COVID-19 ... This systematic review evaluates the incidence, mechanisms, and clinical implications of POTS following COVID-19 vaccination.