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

NCT ID: NCT05764993

Last Updated: 2023-06-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-06-01

Study Completion Date

2025-12-30

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

Conditions

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COPD Exacerbation Acute

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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
Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Group #1

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

Group Type EXPERIMENTAL

CUVITRU - Ig subcutaneous human 20%

Intervention Type BIOLOGICAL

Subcutaneous Immunoglobin Replacement Therapy, SCigR

Standard Medical Therapy

Intervention Type OTHER

Standard Medical Therapy

Group #2

Standard of care management = 20 patients

Group Type PLACEBO_COMPARATOR

Standard Medical Therapy

Intervention Type OTHER

Standard Medical Therapy

Interventions

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CUVITRU - Ig subcutaneous human 20%

Subcutaneous Immunoglobin Replacement Therapy, SCigR

Intervention Type BIOLOGICAL

Standard Medical Therapy

Standard Medical Therapy

Intervention Type OTHER

Other Intervention Names

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Immune Globulin Subcutaneous (Human), 20% Solution

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

82 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Takeda

INDUSTRY

Sponsor Role collaborator

Rochester General Hospital

OTHER

Sponsor Role lead

Responsible Party

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S. Shahzad Mustafa

Principle Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Syed S Mustafa, MD

Role: PRINCIPAL_INVESTIGATOR

Rochester General Hospital

Locations

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Rochester Regional Health Ctr for Clinical Research - Alexander Park

Rochester, New York, United States

Site Status RECRUITING

Rochester Regional Health - Ctr for Clinical Research - Linden Oaks

Rochester, New York, United States

Site Status RECRUITING

Rochester Regional Health - Ctr for Clinical Research - Greece

Rochester, New York, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Dawn Sheflin, RN

Role: CONTACT

585-922-8314

Holly Blue, LPN

Role: CONTACT

585-922-8314

Facility Contacts

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Dawn Sheflin, RN

Role: primary

585-922-8314

Holly Blue, LPN

Role: backup

585-922-8314

Dawn Sheflin, RN

Role: primary

585-922-8314

Holly Blue, LPN

Role: backup

585-922-8314

Dawn Sheflin, RN

Role: primary

585-922-8314

Holly Blue, LPN

Role: backup

585-922-8314

References

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Reference Type BACKGROUND
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Sethi S, Murphy TF. Infection in the pathogenesis and course of chronic obstructive pulmonary disease. N Engl J Med. 2008 Nov 27;359(22):2355-65. doi: 10.1056/NEJMra0800353. No abstract available.

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Sethi S. Infection as a comorbidity of COPD. Eur Respir J. 2010 Jun;35(6):1209-15. doi: 10.1183/09031936.00081409.

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Related Links

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http://www.goldcopd.org

Global initiative for Chronic Obstructive Lung Disease

Other Identifiers

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IISR Protocol

Identifier Type: -

Identifier Source: org_study_id

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