Primary antibody deficiency: - Unclassified antibody deficiency (unPAD) - IgA deficiency - Specific polysaccharide antibody deficiency (SPAD) - IgG subclass deficiency (IgSD) - Common variable immunodeficiency (CVID) - Agammaglobulinemia (X-linked or otherwise)
Conditions
Interventions
Trade Name: Human normal immunoglobulin
Pharmaceutical Form: Concentrate and solvent for solution for injection/infusion
Sponsors
UMC Utrecht
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: In order to be eligible to participate in this study, a subject must meet all of the following criteria: 1. Age 4-60 years 2. Diagnosis of Primary Antibody Deficiency / Common Variable Immunodeficiency Disorder (see Appendix 1). 3. Indication for immunoglobulin replacement therapy and/or treated with immunoglobulin replacement therapy 4. Current IgG dosing 0.4 - 0.6 gr / kg / 3-4 weeks 5. Receiving treatment and follow up for PAD by one of the physicians in the participating centers 6. Written informed consent 7. Normal lung status, or mild to medium severe pulmonary disease (measured by pulmonary function test and on CT scan, scored by an independent radiologist based on the following criteria): a. Baseline AD score 5 and/or ILD score > 7 without clinical diagnosis of severe respiratory insufficiency (defined as: saturations in room air 70% expected for age and body weight / length) Are the trial subjects under 18? yes Number of subjects for this age range: 50 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 50 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: A potential subject who meets any of the following criteria will be excluded from participation in this study: 1. Age above 60 year 2. Diagnosis of Combined Immunodeficiency (CID) disease at onset of study (see Appendix A). Explanation: Combined Immunodeficiency is featured by the occurrence of more viral infections and reactivations and thus less comparable to PAD. 3. Severe pulmonary disease, determined by an independent radiologist: a. Baseline AD score > 5 and/or ILD score > 7, in combination with: i. Saccular bronchiectasis on CT scan, or; ii. Clinical diagnosis of severe respiratory insufficiency (defined as: (defined as: saturations in room air 70% expected for age and body weight / length)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Difference in mean AD and ILD scores (as measured with CT scanning) between t=0 and t=2 years in patients with standard vs higher Ig replacement therapy dosing. ;Secondary Objective: 1.The incidence of symptomatic lower pulmonary infections in PAD patients with high Ig replacement therapy dosing versus standard Ig replacement therapy dosing. 2.Number of physician diagnosed lower respiratory tract infections in patients with high vs standard Ig replacement therapy dosing. 3.Number of hospital admissions and duration of hospital admissions for pulmonary complications (ao exacerbations of bronchiectasis) 4.Outcomes of pulmonary function tests (specifically: Total Lung Capacity (TLC), Forced Expiratory Volume after 1 second (FEV1), CO diffusion) on t=0 and t=2 years in all patients 5.Days missed from work / school in patients with high vs standard Ig replacement therapy dosing. 6.Total therapeutic and preventive costs ;Primary end point(s): The main outcome parameters of this study are rate of progression of AD an ILD after 24 months in patients receiving a higher dose of Ig medication versus patients receiving standard Ig dosing, and the associated decrease in health costs. To measure this main outcome parameter we will use a disease specific CT scoring method that was developed and validated specifically for monitoring of lung disease in PAD (9,10). The scoring method was shown to be accurate and reproducible. By protocol, CT scans are made at t = 0 and t = 2 years. It is however possible that clinical symptoms or situations arise during the study period within a participant, so that an additional CT scan is indicated. The reasons for making an extra CT scan (following current clinical practice guidelines) are: -Symptoms of dyspnea accompanied by low saturations (<92%) -A lung function (FVC or FEV1) below 80% of expected value for age and length / body weight -Abnormalities on a chest X-ray making a CT scan necessary (made for indications | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Number of upper- and lower respiratory tract infections before onset of study and during study, i.e.: Sino pulmonary disease, otitis, pneumonia, collected by study CRF’s. 2. Pulmonary symptoms will be evaluated on a daily basis (during two periods of 2 months) using a diary that can be directly entered in Castor. 3. Days missed from school and work due to infections, measured by the PCQ (productivity cost questionnaire) instrument. 4. Quality of life, measured with the EQ-5D questionnaire 5. Ig dosing and IgG trough levels in intervention and in control group 6. Total health costs (consisting of costs for health care professional visits, medication, hospitalizations, imaging and biochemical investigations) in intervention and control group, collected from electronic patient files. 7. Immunological laboratory phenotype, collected from electronic patient files. 8. Adverse events: reporting and monitoring of patients and Adverse Events (AEs), Serious Adverse Events (SAEs) and Suspected Unexpected Serious Adverse Reaction (SUSARs) will be done by an independent monitor. ;Timepoint(s) of evaluation of this end point: Point 1 and 8 will be measured continiously. Point 2 will be evaluated during two periods of 2 months. Point 3,4 and 7 will be evaluated at baseline, after 12 months and after 24 months. Point 5 will be evaluated at baseline, after 1 month, after 2 months, after 6 months, after 8 months, after 12 months and after 24 months Point 7 will be evaluated at the end of the study | — |
Countries
Netherlands
Contacts
Public ContactJoris van Montfrans
UMC Utrecht
Outcome results
None listed