Prevalence of Humoral Dysfunction in Pts With Frequent Exacerbations of COPD, and the Effect of SCIgR for Prevention

Study Overview
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Brief Summary
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To examine the prevalence of humoral immunodeficiency in patients with Chronic Obstructive Pulmonary disease (COPD) by evaluating both immunoglobulin levels and vaccine responses. Patients with COPD and humoral dysfunction will be offered treatment with Subcutaneous Immune Globulin Replacement Therapy (SCIgR) in an attempt to decrease future AECOPD.

Detailed Description
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This will be a non-blinded, randomized study. Patients with COPD will be referred for evaluation by outpatient pulmonary clinics at Rochester Regional health. Following informed consent all patients will be evaluated by checking serum IgG, IgM, and IgA, as well as baseline and post-vaccine IgG to peptides antigens (diphtheria and tetanus) with Td as well as polysaccharide antigens (streptococcus pneumoniae) with pneumococcus polyvalent vaccine-23 (PPV23). Patients with COPD and pre-defined humoral dysfunction (please see below) will be randomized in 1:1 ratio to one of two groups until approximately 20 patients per group are accrued for a total of 40 patients Group #1: SCIgR with Cuvitru 125 mg/kg/week + standard of care management = 20 patients Group #2: Standard of care management = 20 patients

Official Title
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Prevalence of Humoral Immune Deficiency in Patients With Frequent Exacerbations of COPD, and the Effect of Immunoglobulin Replacement on Future Exacerbations

Conditions
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COPD Exacerbation Acute

Intervention / Treatment
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* Biological: CUVITRU - Ig subcutaneous human 20%
* Other: Standard Medical Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients > 18 years and ≤ 82 years old. Patient that meet three (3) or more of the five (5) following criteria. Dyspnea ≥ 5 on a visual analog scale Respiratory rate ≥ 24 breaths per minute Heart rate ≥ 95 beats per minute Resting SaO2 < 92% breathing ambient air of the patient's usual oxygen prescription and/or change in saturation > 3% from baseline CRP ≥ 10 mg/L Established diagnosis of COPD with PFTs showing FEV1/FVC < 70% or FEV1/VC ratio below the 5th percentile of the predicted value.[14] Subjects must have adherence with triple therapy [Inhaled Corticosteroid (ICS), Long-acting beta2-adrenergic agonist (LABA), Long-acting muscarinic antagonist (LAMA)] for greater than 90 Days prior to consideration of participation in this study. With triple therapy onboard, the subject must have ≥ 2 steroid-requiring exacerbations (defined by increased respiratory symptoms of increased cough, dyspnea, sputum, sputum purulence, wheeze, chest tightness) requiring treatment with systemic steroids within the past 12 months OR one exacerbation requiring inpatient hospitalization Medically stable with no acute hospitalizations for non-COPD related events within the last 3 months Expected life expectancy > 1 year Stable Cardiovascular Disease, with no planned intervention No history of pulmonary embolism or embolic event Hepatic function < Class B Child-Pugh criteria Renal insufficiency with eGFR > 60 mL/min/1.73m2 No history of DVT or thrombotic events No history of prior organ transplant Female subjects of childbearing potential will need to have a negative pregnancy test performed within 14 days prior to study procedure (if applicable) and be adherent to an accepted method of contraception. Male subject will need to adhere to barrier contraception during the course of the trial and for 1 month after completion of the final injection of Cuvitru. Ability to sign informed consent Exclusion criteria: Known history of humoral dysfunction/immunodeficiency Known hereditary/genetic/congenital defects, and autoimmune disease including hereditary spherocytosis, hereditary elliptocytosis, paroxysmal nocturnal hemoglobinuria, and sickle cell disease Ongoing or recent therapy with immunoglobulin replacement therapy within the past 6 months Chronic oral steroid use of prednisone treatment of ≥20 mg daily (or equivalent) will be excluded to ensure subject is medically stable. Alpha-1 antitrypsin deficiency Obesity with a BMI > 40 Unstable hypertension systolic blood pressure (SBP) >160 mmHg upon repeated measure Diabetes mellitus Type I Known history of acquired or inherited thrombophilia disorders Known risk factors of hemolysis, including G6PD deficiency, mitral valve replacement, aortic valve replacement. Known prolonged periods of immobilization Known severe hypovolemia noted by SBP ≤ 85 and/or heart rate (HR) >130 Known hypercoagulable conditions Use of estrogens Indwelling central vascular catheters Currently actively smoking

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 82 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: non-blinded, randomized study. Patients with COPD will be referred for evaluation by outpatient pulmonary clinics at Rochester Regional health. Following informed consent all patients will be evaluated by checking serum IgG, IgM, and IgA, as well as baseline and post-vaccine IgG to peptides antigens (diphtheria and tetanus) with Td as well as polysaccharide antigens (streptococcus pneumoniae) with pneumococcus polyvalent vaccine-23 (PPV23). Patients with COPD and pre-defined humoral dysfunction (please see below) will be randomized in 1:1 ratio to one of two groups until approximately 20 patients per group are accrued for a total of 40 patients
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group #1<br>SCIgR with Cuvitru 125 mg/kg/week + standard of care management | Biological: CUVITRU - Ig subcutaneous human 20%<br>* Subcutaneous Immunoglobin Replacement Therapy, SCigR<br>* Other names: Immune Globulin Subcutaneous (Human), 20% Solution;Other: Standard Medical Therapy<br>* Standard Medical Therapy<br>|
| Placebo Comparator: Group #2<br>Standard of care management = 20 patients | Other: Standard Medical Therapy<br>* Standard Medical Therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AECOPD requiring treatment with systemic steroids over one year | AECOPD is defined by increased respiratory symptoms (e.g., cough, dyspnea, sputum, sputum purulence, wheeze, chest tightness) requiring treatment with systemic steroids. | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| COPD with pre-defined humoral dysfunction treated with subcutaneous SCIgR will have decreased AECOPD events as compared to COPD with pre-defined humoral dysfunction treated with the standard of care (SOC) management. | AECOPD events will be determined by evaluating the rate of re-hospitalization in both treatment groups (ie with subcutaneous SCIgR + SOC versus SOC). The treatment group with subcutaneous SCIgR + SOC will have decreased AECOPD events as evidenced by the lower rehospitalization rate in comparison to the SOC treatment group's rehospitalization rate. | one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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humoral dysfunction, humoral immune function