IgPro20 for POTS

Recruiting at 41 trial locations

Overseen By Trial Registration Coordinator

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: CSL Behring

Must not be taking: Immunoglobulin G, Plasmapheresis

Disqualifiers: Neurologic, Autoimmune, Endocrine, others

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 5 Jurisdictions

Trial Summary

What is the purpose of this trial?

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 \[post-COVID-POTS\]).

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.

What data supports the effectiveness of the drug IgPro20 for treating POTS?

The drug IgPro20 has been shown to be effective in maintaining stable IgG levels and protecting against infections in patients with primary immunodeficiency, with fewer side effects compared to intravenous administration. While this data is specific to primary immunodeficiency, it suggests that IgPro20 can effectively maintain necessary immune function, which may be relevant for its use in other conditions like POTS. ^{1 2 3 4 5}

Is IgPro20 safe for use in humans?

IgPro20, also known as Hizentra, has been shown to be generally safe for humans, with most side effects being mild or moderate. In studies with patients having primary immunodeficiency, no serious side effects related to IgPro20 were reported, and it was well tolerated. ^{2 3 4 5 6}

How does the drug IgPro20 differ from other treatments for POTS?

IgPro20 is unique because it is administered subcutaneously (under the skin) rather than intravenously, which can offer more consistent IgG levels and fewer side effects. It is also stabilized with L-proline, enhancing its stability and tolerability. ^{3 4 5 7 8}

Research Team

Study Director

Principal Investigator

CSL Behring

Eligibility Criteria

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 am 18 years old or older.

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.

Trial Timeline

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

Treatment Details

Interventions

• IgPro20 (Monoclonal Antibodies)

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.

Participant Groups

Group I: IgPro20 Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

IgPro20 is already approved in Canada, Japan, Switzerland for the following indications:

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

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Cost-minimization analysis of IgPro20, a subcutaneous immunoglobulin, in Japanese patients with primary immunodeficiency. [2018]

2. Netherlands 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. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy and safety of a new 20% immunoglobulin preparation for subcutaneous administration, IgPro20, in patients with primary immunodeficiency. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Population pharmacokinetic analysis of weekly and biweekly IgPro20 (Hizentra®) dosing in patients with primary immunodeficiency. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of subcutaneous IgPro20 in patients with primary immunodeficiency. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

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

7. New Zealand pubmed.ncbi.nlm.nih.gov

Immune Globulin Subcutaneous (Human) 20% (Hizentra®): A Review in Chronic Inflammatory Demyelinating Polyneuropathy. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Switch from intravenous to subcutaneous immunoglobulin IgPro20 in CIDP patients: a prospective observational study under real-world conditions. [2022]