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

Trial Summary

What is the purpose of this trial?

Although there is evidence in the literature that gammaglobulin replacement therapy can lead to a reduction in the prevalence of pulmonary infection and improved lung function, there is no published study to guide immunologists regarding the use of spirometry in titrating IG therapy to assist in the management of immunodeficiency patients with regards to gammaglobulin replacement therapy. The investigators propose to study the use of spirometry to identify patients that could potentially benefit from an increase in IGRT. The investigators will identify 22 common variable immune deficiency (CVID) study subjects on stable IGRT replacement therapy equivalent to 0.40 to 0.60 gm/kg per 4 weeks who have evidence of mild to moderate obstruction as assessed by an FEF25-75% between 50% and 80% of predicted. Patients who are on Hizentra will be preferentially recruited. Of these 22, 11 will be identified at random and treated for 6 months at their current dose (control population). The remaining 11 study subjects (treatment group) will have their level of IGRT 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.

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 data supports the effectiveness of the drug Hizentra for treating common variable immunodeficiency?

Hizentra, a subcutaneous immunoglobulin, has been shown to maintain or increase IgG levels in patients, providing effective protection against serious bacterial infections in both adults and children with primary immunodeficiency. It is well-tolerated, can be self-administered, and offers convenience with shorter infusion times, making it a beneficial option for home therapy. ^{1 2 3 4 5}

Is Hizentra safe for use in humans?

Hizentra, a subcutaneous immunoglobulin therapy, is generally safe and well-tolerated in humans, with most adverse effects being mild, such as local injection site reactions. It has been used effectively in both adults and children with primary immunodeficiencies, showing no serious treatment-related adverse events in multiple studies. ^{1 2 4 6 7}

How is the drug Hizentra different from other treatments for common variable immunodeficiency?

Hizentra is unique because it is a highly concentrated (20%) liquid form of immunoglobulin G (IgG) that is administered subcutaneously (under the skin), allowing for self-administration at home. This method offers more convenience and flexibility compared to traditional intravenous (IV) administration, with shorter infusion times and the option for biweekly dosing, which can improve the quality of life for patients. ^{3 4 5 8 9}

Research Team

Harry Schroeder, MD/PhD

Principal Investigator

University of Alabama at Birmingham

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

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]

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]

References

1. 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]

2. Netherlands pubmed.ncbi.nlm.nih.gov

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

3. England pubmed.ncbi.nlm.nih.gov

Hizentra for the treatment of primary immunodeficiency. [2014]

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

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

5. Australia pubmed.ncbi.nlm.nih.gov

Real-world results with IgPro20 for hypo- or agammaglobulinemia in Japan. [2023]

6. United States 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. [2011]

7. Netherlands 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. [2020]

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

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

9. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetic modeling and simulation of biweekly subcutaneous immunoglobulin dosing in primary immunodeficiency. [2013]