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

Rochester General Hospital

Status and phase: Enrolling; Phase 2

Conditions: COPD Exacerbation Acute

Treatments: Other: Standard Medical Therapy; Biological: CUVITRU - Ig subcutaneous human 20%

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05764993

IISR Protocol

Details and patient eligibility

About

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.

Full description

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

Enrollment: 40 estimated patients

Sex: All

Ages: 18 to 82 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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40 participants in 2 patient groups, including a placebo group

Group #1

Experimental group

Description:

SCIgR with Cuvitru 125 mg/kg/week + standard of care management

Treatment:

Biological: CUVITRU - Ig subcutaneous human 20%

Other: Standard Medical Therapy

Group #2

Placebo Comparator group

Description:

Standard of care management = 20 patients

Treatment:

Other: Standard Medical Therapy