Usage of Spirometry in Managing IgG Therapy in CVID With Airway Disease

A Prospective Study of the Utility of Spirometry to Identify and Manage Immunoglobulin Replacement Dosage in Primary Antibody Deficiency in Patients With Potentially Reversible Airway Disease

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.

Study Overview

• Status: Recruiting
• Conditions: Common Variable Immunodeficiency
• Intervention / Treatment: Drug: Hizentra

Detailed Description

The key finding of the published retrospective study was that common variable immune deficiency (CVID) patients with moderate, presumed reversible, obstruction on stable, therapeutic doses of IgG who exhibited a decline in lung function from one clinic visit to the next responded to an increased dose of IgG with an improvement in lung function as assessed by spirometry.

The investigators now wish perform a clinical trial to assess whether primary antibody deficiency patients receiving IGRT who fit in this range of obstruction, i.e. an FEF25-75% that is 50-80% of predicted, will demonstrate an increase in lung function, as assessed by spirometry, after increasing the dose of IGRT. The presumption is that obstruction at this level is most likely due to the effects of subclinical infections that can be reduced or avoided by increasing the amount of gammaglobulin received by the patients.

• Study Type: Interventional
• Enrollment (Estimated): 22
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Leigh Powell; Phone Number: 2053319159; Email: lcpowell@uabmc.edu
• Study Contact Backup: Name: Tracy Hwangpo, MD/PhD; Phone Number: 2059960161; Email: thwangpo@uabmc.edu

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Recruiting
      • Community Health 20
      • Contact: Tracy Hwangpo, MD; Phone Number: 205-996-0161; Email: thwangpo@uabmc.edu
      • Contact: Melanese Leonard, MSN, RN; Phone Number: 205-490-4179; Email: mnleonard@uabmc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Patients who meet criteria for common variable immune deficiency (CVID) who are on stable IGRT for at least 3 months and who have an FEF25-75% between 50% and 80% of predicted.
2. Patients who are already on Hizentra will be preferred.

Exclusion Criteria:

1. Age <21 or cannot perform spirometry.
2. Smokers with 20 pack years or more, and active smokers will not be included among the study subjects, but will be considered separately as an ancillary study.
3. 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.
4. Patients with heart failure, TB, bronchiolitis, or lymphangioleiomyomatosis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control Group; 11 subjects will be treated for 6 months at their current dose of Hizentra
Experimental: Treatment Group; 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.	Drug: Hizentra; subjects level of immunoglobulin replacement therapy will be adjusted for bioavailability as per manufacturer's instructions; Other Names: subcutaneous gammaglobulin therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FEV1 at baseline	Pulmonary function will be measured by forced expiratory volume in one second (FEV1) at baseline.	baseline
FEV1 at 3 months	Pulmonary function will be measured by forced expiratory volume in one second (FEV1) at three months into the study.	3 months
FEV1 at 6 months.	Pulmonary function will be measured by forced expiratory volume in one second (FEV1) at six months into the study.	6 months
FVC at baseline	Pulmonary function will be measured by forced vital capacity (FVC) at baseline.	baseline
FVC at 3 months	Pulmonary function will be measured by forced vital capacity (FVC) at three months.	3 months
FVC at 6 months.	Pulmonary function will be measured by forced vital capacity (FVC) at six months.	6 months
FEF25-75% at baseline	Pulmonary function will be measured by forced expiratory flow at 25 and 75% of the pulmonary volume (FEF25-75%) at baseline.	baseline
FEF25-75% at 3 months	Pulmonary function will be measured by forced expiratory flow at 25 and 75% of the pulmonary volume (FEF25-75%) at 3 months.	3 months
FEF25-75% at 6 months	Pulmonary function will be measured by forced expiratory flow at 25 and 75% of the pulmonary volume (FEF25-75%) at six months.	6 months
FEV1/FVC ratio at baseline	FEV1/FVC ratio will be calculated at baseline. The FEV1/FVC ratio is the ratio of the forced expiratory volume in the first one second (FEV1) to the forced vital capacity (FVC) of the lungs.	baseline
FEV1/FVC ratio at 3 months	FEV1/FVC ratio will be calculated at 3 months. The FEV1/FVC ratio is the ratio of the forced expiratory volume in the first one second (FEV1) to the forced vital capacity (FVC) of the lungs.	3 months
FEV1/FVC ratio at 6 months	FEV1/FVC ratio will be calculated at 6 months. The FEV1/FVC ratio is the ratio of the forced expiratory volume in the first one second (FEV1) to the forced vital capacity (FVC) of the lungs.	6 months
FOT at baseline.	Forced Oscillation Technique (FOT) will be measured at baseline. Forced Oscillation Technique (FOT) measures lung impedance during tidal breathing.	baseline
FOT at 3 months.	Forced Oscillation Technique (FOT) will be measured at 3 months. Forced Oscillation Technique (FOT) measures lung impedance during tidal breathing.	3 months
FOT at 6 months.	Forced Oscillation Technique (FOT) will be measured at 6 months. Forced Oscillation Technique (FOT) measures lung impedance during tidal breathing.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FACIT score at baseline and monthly on therapy	assess the effect of increasing the dose of IGRT on the patients' well-being by quantitating their fatigue level. Scores range from zero (no fatigue) to 52 (maximum fatigue/worse outcome).	6 months
PADQOL-16 at baseline and monthly on therapy	assess the effect of increasing the dose of IGRT on the patients' well-being by quantitating their quality of life. Scores range from zero (no impairment) to 32 (maximum impairment/worse outcome).	6 months
St. George's Respiratory Questionnaire at baseline and monthly on therapy	Disease-specific instrument designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease. Scores range from zero (no impairment) to 100 (maximum impairment/worse outcome).	6 months

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Collaborators: CSL Behring
• Investigators: Principal Investigator: Harry Schroeder, MD/PhD, University of Alabama at Birmingham

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: August 6, 2021
• First Submitted That Met QC Criteria: December 27, 2021
• First Posted (Actual): January 18, 2022

Study Record Updates

• Last Update Posted (Actual): May 4, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Immunologic Deficiency Syndromes; Common Variable Immunodeficiency; Immunologic Factors; Physiological Effects of Drugs; Hizentra
• Other Study ID Numbers: I300005696; 2024805 (Other Identifier: CSL Behring)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes