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

The University of Alabama at Birmingham

Status and phase: Enrolling; Phase 4

Conditions: Common Variable Immunodeficiency

Treatments: Drug: Hizentra

Study type: Interventional

Funder types: Other

Identifiers

NCT05193552

I300005696

Details and patient eligibility

About

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.

Full 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.

Enrollment: 22 estimated patients

Sex: All

Ages: 21+ years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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22 participants in 2 patient groups

Control Group

No Intervention group

Description:

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

Treatment Group

Experimental group

Description:

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.

Treatment:

Drug: Hizentra