Examining immune dysfunction in COPD patients and its treatment

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

This study is testing if a new immune therapy can help people with COPD who have low antibody levels experience fewer flare-ups of their condition.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years to 82 Years
• Sex: All
• Sponsor: Rochester General Hospital (Academic / other)
• Drugs / interventions: prednisone
• Locations: 3 sites (Rochester, New York and 2 other locations)
• Trial ID: NCT05764993 on ClinicalTrials.gov

What this trial studies

This study investigates the prevalence of humoral immunodeficiency in patients with Chronic Obstructive Pulmonary Disease (COPD) by assessing immunoglobulin levels and vaccine responses. Patients identified with humoral dysfunction will be randomized to receive either Subcutaneous Immune Globulin Replacement Therapy (SCIgR) or standard care management. The aim is to determine if SCIgR can reduce the frequency of acute exacerbations of COPD. The study will involve evaluations at outpatient pulmonary clinics and will include a total of 40 patients.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 82 with a diagnosis of COPD and a history of frequent exacerbations despite standard therapy.

Not a fit: Patients without humoral dysfunction or those not meeting the inclusion criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved management and reduced exacerbations for COPD patients with humoral dysfunction.

How similar studies have performed: Other studies have shown promise in treating humoral dysfunction in similar patient populations, suggesting potential for success in this approach.

Eligibility criteria

Inclusion criteria:

1. Patients \> 18 years and ≤ 82 years old.
2. Patient that meet three (3) or more of the five (5) following criteria.

   1. Dyspnea ≥ 5 on a visual analog scale
   2. Respiratory rate ≥ 24 breaths per minute
   3. Heart rate ≥ 95 beats per minute
   4. Resting SaO2 \< 92% breathing ambient air of the patient's usual oxygen prescription and/or change in saturation \> 3% from baseline
   5. CRP ≥ 10 mg/L
3. Established diagnosis of COPD with PFTs showing FEV1/FVC \< 70% or FEV1/VC ratio below the 5th percentile of the predicted value.\[14\]
4. 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.
5. 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
6. Medically stable with no acute hospitalizations for non-COPD related events within the last 3 months
7. Expected life expectancy \> 1 year
8. Stable Cardiovascular Disease, with no planned intervention
9. No history of pulmonary embolism or embolic event
10. Hepatic function \< Class B Child-Pugh criteria
11. Renal insufficiency with eGFR \> 60 mL/min/1.73m2
12. No history of DVT or thrombotic events
13. No history of prior organ transplant
14. 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.
15. 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.
16. Ability to sign informed consent

Exclusion criteria:

1. Known history of humoral dysfunction/immunodeficiency
2. Known hereditary/genetic/congenital defects, and autoimmune disease including hereditary spherocytosis, hereditary elliptocytosis, paroxysmal nocturnal hemoglobinuria, and sickle cell disease
3. Ongoing or recent therapy with immunoglobulin replacement therapy within the past 6 months
4. Chronic oral steroid use of prednisone treatment of ≥20 mg daily (or equivalent) will be excluded to ensure subject is medically stable.
5. Alpha-1 antitrypsin deficiency
6. Obesity with a BMI \> 40
7. Unstable hypertension systolic blood pressure (SBP) \>160 mmHg upon repeated measure
8. Diabetes mellitus Type I
9. Known history of acquired or inherited thrombophilia disorders
10. Known risk factors of hemolysis, including G6PD deficiency, mitral valve replacement, aortic valve replacement.
11. Known prolonged periods of immobilization
12. Known severe hypovolemia noted by SBP ≤ 85 and/or heart rate (HR) \>130
13. Known hypercoagulable conditions
14. Use of estrogens
15. Indwelling central vascular catheters
16. Currently actively smoking

Where this trial is running

Rochester, New York and 2 other locations

• Rochester Regional Health Ctr for Clinical Research - Alexander Park — Rochester, New York, United States (Recruiting)
• Rochester Regional Health - Ctr for Clinical Research - Linden Oaks — Rochester, New York, United States (Recruiting)
• Rochester Regional Health - Ctr for Clinical Research - Greece — Rochester, New York, United States (Recruiting)

Study contacts

• Principal investigator: Syed S Mustafa, MD — Rochester General Hospital
• Study coordinator: Dawn Sheflin, RN

Conditions COPD Exacerbation Acute; humoral dysfunction; humoral immune function