Spirometry and IgG Therapy for Common Variable Immunodeficiency

Overseen By Tracy Hwangpo, MD/PhD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Alabama at Birmingham

Must be taking: IGRT

Disqualifiers: Age <21, Smokers, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 6 months

22 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called Hizentra (a subcutaneous immunoglobulin therapy) to determine if adjusting its dose can improve lung function in people with common variable immune deficiency (CVID). Researchers aim to discover if spirometry (a breathing test) can guide when to increase the dose of immunoglobulin replacement therapy (IGRT) to reduce lung infections. Participants with CVID who have been on a stable IGRT dose for at least 3 months and experience mild to moderate breathing issues may be suitable for this study. As a Phase 4 trial, this research seeks to understand how this already FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

The trial does not specify whether you need to stop taking your current medications. However, it seems that participants need to be on stable IGRT (immunoglobulin replacement therapy) for at least 3 months before joining the study.

What is the safety track record for Hizentra?

Research has shown that Hizentra is generally safe for people with common variable immunodeficiency (CVID). Studies have found that it helps maintain or even boost IgG levels, which are crucial for fighting infections. Most patients with CVID tolerate Hizentra well, even at higher doses. Evidence also indicates that Hizentra can be safely used in various infusion settings, which suggests good overall tolerability. Furthermore, the FDA has already approved Hizentra for treating primary immunodeficiency, supporting its safety. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Hizentra is unique because it allows for a flexible adjustment in immunoglobulin replacement therapy, specifically tailored to the needs of individuals with Common Variable Immunodeficiency (CVID). Unlike traditional treatments that maintain a static dosage, this approach increases the dose by about 2 grams per week, potentially improving the body's immune response. Researchers are excited about this treatment because it offers a more personalized and potentially more effective way to manage CVID, aiming for better protection against infections by fine-tuning the therapy to each patient's requirements.

What evidence suggests that spirometry-guided IG therapy could be effective for common variable immunodeficiency?

Research has shown that Hizentra, a type of immune therapy, is effective for people with common variable immunodeficiency (CVID). Studies have demonstrated that Hizentra can improve or maintain levels of IgG, a protein that helps fight infections. These studies also found that Hizentra reduces the frequency of infections in patients. Long-term evidence supports its effectiveness and safety for extended use. In this trial, participants in the treatment group will receive an increased level of immunoglobulin replacement therapy, while those in the control group will continue at their current dose. The treatment enhances the immune system by providing extra antibodies. ^{1 2 6 7 8}

Who Is on the Research Team?

Harry Schroeder, MD/PhD

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

This trial is for people with Common Variable Immunodeficiency (CVID) who've been on stable immunoglobulin replacement therapy (IGRT) for at least 3 months. They should have specific lung function test results showing mild to moderate obstruction. Preference is given to those already using Hizentra.

Inclusion Criteria

I am currently taking Hizentra.

I have CVID, been on IGRT for 3+ months, and my lung function is moderately reduced.

Exclusion Criteria

I am under 21 years old or unable to perform a lung function test.

I have heart failure, TB, bronchiolitis, or lymphangioleiomyomatosis.

Patients with specific antigen-specific antibody deficiencies or X-linked agammaglobulinemia on IGRT will not be included among the 20 study subjects, but will be considered separately in ancillary studies

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Baseline measurements of lung function using FOT, FEV1/FVC ratio, FEF25-75%, and FVC

1 week

1 visit (in-person)

Treatment

Participants receive either stable or increased dose of IGRT for 6 months

6 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Hizentra

Trial Overview The study tests if using spirometry, a lung function test, can help adjust the dose of IGRT in CVID patients with airway disease. Half will continue their current IGRT dose; the other half will receive an increased dose of Hizentra for six months.

How Is the Trial Designed?

Group I: Treatment Group Experimental Treatment 1 Intervention

11 subjects will have their level of immunoglobulin replacement therapy increased by the equivalent of 0.05 gm/kg in dose per 4 weeks, adjusted for bioavailability as per manufacturer's instructions. On average, rounded up to the nearest gram, this will typically increase their dose of Hizentra by 2 gm per week.

Group II: Control Group Active Control 1 Intervention

11 subjects will be treated for 6 months at their current dose of Hizentra

Hizentra is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Hizentra for:

• Primary Humoral Immunodeficiency (PI)

Approved in European Union as Hizentra for:

• Primary Immunodeficiency Syndromes

Approved in Canada as Hizentra for:

• Primary Immunodeficiency Disorders

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Published Research Related to This Trial

A 35-year-old woman with common variable immune deficiency showed a significant reduction in infection rates after switching from intravenous immunoglobulin (IVIg) therapy to subcutaneous immunoglobulin (SCIg) therapy, indicating improved efficacy with the latter.

The patient's IgG3 levels, which were undetectable during IVIg treatment, increased significantly during SCIg therapy, suggesting that monitoring IgG3 levels could be a useful way to assess the effectiveness of immunoglobulin replacement therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved IgG3 levels and reduced infection rate in a woman with CVID switched from intravenous to subcutaneous immunoglobulin therapy. Shapiro, RS.[2012]

Hizentra® (subcutaneous IgG) was shown to be effective and well-tolerated in a large cohort of 125 patients over a total observation period of 250.9 patient-years, with low rates of infections (3.10 events per patient/year) and serious bacterial infections (0.03 events per patient/year).

The therapy resulted in increased serum IgG levels for patients switching from intravenous IgG, and most adverse events were mild or moderate, with injection site reactions being the most common, indicating a favorable safety profile for long-term use in patients with primary immunodeficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Efficacy and Safety of Hizentra® in Patients with Primary Immunodeficiency in Japan, Europe, and the United States: a Review of 7 Phase 3 Trials. Jolles, S., Rojavin, MA., Lawo, JP., et al.[2020]

In a real-world study of 85 patients receiving IgPro20 for hypogammaglobulinemia, 45.9% experienced adverse events, with injection site reactions being the most common, but the treatment was generally considered safe.

The effectiveness of IgPro20 was demonstrated by a reduction in infection rates from 0.54 per patient before treatment to 0.39 during treatment, indicating it helps protect against infections in patients with primary and secondary immunodeficiencies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world results with IgPro20 for hypo- or agammaglobulinemia in Japan. Imai, K., Ishii, T., Nonoyama, S., et al.[2023]

Subcutaneous Hizentra(®) treatment for primary immunodeficiencies in children is effective, maintaining or increasing IgG levels without serious bacterial infections reported during the 40-week study involving 23 participants.

The treatment is well-tolerated, with a low incidence of adverse events, and is particularly suitable for children as it avoids the need for venous access and has minimal systemic side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of hizentra®, a new 20% immunoglobulin preparation for subcutaneous administration, in pediatric patients with primary immunodeficiency. Borte, M., Pac, M., Serban, M., et al.[2021]

Hizentra(®), a 20% concentrated IgG solution for subcutaneous infusion, offers improved safety and tolerability for patients with primary immunodeficiency disease, enhancing their protection from infections.

The use of highly concentrated IgG products like Hizentra allows for flexible dosing and shorter infusion times, which can lead to better patient adherence to therapy and improved quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hizentra for the treatment of primary immunodeficiency. Wasserman, RL.[2014]

In a Phase III study involving 51 patients with primary immunodeficiency, Hizentra(®), a 20% human IgG for subcutaneous use, effectively maintained or improved serum IgG levels without requiring dose increases over a 40-week period.

The treatment was safe, with no serious bacterial infections reported and mostly mild local reactions occurring at a low rate, indicating that Hizentra(®) is a well-tolerated option for patients transitioning from intravenous to subcutaneous immunoglobulin therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of Hizentra(®) in patients with primary immunodeficiency after a dose-equivalent switch from intravenous or subcutaneous replacement therapy. Jolles, S., Bernatowska, E., de Gracia, J., et al.[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]

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]

A new population pharmacokinetic model was created using data from 151 patients to predict IgG levels for different administration routes and schedules, enhancing treatment for primary immunodeficiency.

The model suggests that biweekly subcutaneous (SC) dosing of Hizentra can maintain stable IgG levels similar to weekly dosing, providing patients with more flexible treatment options and potentially improving their quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic modeling and simulation of biweekly subcutaneous immunoglobulin dosing in primary immunodeficiency. Landersdorfer, CB., Bexon, M., Edelman, J., et al.[2013]

Citations

1. labeling.cslbehring.com labeling.cslbehring.com/product-document/US/Hizentra/EN/Hizentra-P&T-Summary.pdf

Hizentra® P&T summary - CSL Behring Hizentra is a ready-to-use, sterile 20% (0.2 g/mL) protein liquid preparation of polyvalent human immunoglobulin G (IgG) for subcutaneous administration.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6292970/

Long-Term Efficacy and Safety of Hizentra® in Patients with ... The results from these seven studies indicate that Hizentra® therapy was both efficacious and well tolerated during long-term treatment.

3. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1532367/full

data of a GEIE Spanish Registry This study, conducted by expert immunodeficiency nursing teams, assesses the clinical characteristics, reported adverse effects, and quality-of-life outcomes ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2935641/

Immune Globulin Subcutaneous (Human), 20% Liquid - PMC The route was successfully used in a woman with common variable immunodeficiency and splenectomy, as reported by investigators in 1982 (Berger 1982). Another ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1521661611001884

Efficacy and safety of Hizentra® in patients with primary ... Hizentra maintained or improved serum IgG levels without dose increases and effectively protected patients against infections.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10611600/

Real-World Use, Safety, and Patient Experience of 20% ... Common variable immunodeficiency (CVID) represented the most common type of PID in this patient population (58.3%). Patients most commonly ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03033745

Study Details | NCT03033745 | Safety and Tolerability of ... This multicenter, open-label, parallel-arm, non-randomized study is designed to evaluate safety and tolerability of higher infusion parameters of IgPro20 in ...

8. fda.gov fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM203150.pdf

Package Insert - Hizentra HIZENTRA is an Immune Globulin Subcutaneous (Human) (IGSC), 20% Liquid indicated for the treatment of the following conditions: 1.1 Primary Immunodeficiency (PI).