Ignite Creation Date:
2025-12-25 @ 1:11 AM
Ignite Modification Date:
2025-12-25 @ 11:22 PM
Study NCT ID:
NCT05764993
Status:
RECRUITING
Last Update Posted:
2023-06-15
First Post:
2022-11-29
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Prevalence of Humoral Dysfunction in Pts With Frequent Exacerbations of COPD, and the Effect of SCIgR for Prevention
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'interventionBrowseModule': {'meshes': [{'id': 'D005719', 'term': 'gamma-Globulins'}, {'id': 'D012996', 'term': 'Solutions'}], 'ancestors': [{'id': 'D007136', 'term': 'Immunoglobulins'}, {'id': 'D007162', 'term': 'Immunoproteins'}, {'id': 'D001798', 'term': 'Blood Proteins'}, {'id': 'D011506', 'term': 'Proteins'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D012712', 'term': 'Serum Globulins'}, {'id': 'D005916', 'term': 'Globulins'}, {'id': 'D004364', 'term': 'Pharmaceutical Preparations'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'PREVENTION', 'interventionModel': 'PARALLEL', 'interventionModelDescription': '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'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 40}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2023-06-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2023-06', 'completionDateStruct': {'date': '2025-12-30', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2023-06-13', 'studyFirstSubmitDate': '2022-11-29', 'studyFirstSubmitQcDate': '2023-02-28', 'lastUpdatePostDateStruct': {'date': '2023-06-15', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2023-03-13', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2025-02-28', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'AECOPD requiring treatment with systemic steroids over one year', 'timeFrame': 'one year', 'description': 'AECOPD is defined by increased respiratory symptoms (e.g., cough, dyspnea, sputum, sputum purulence, wheeze, chest tightness) requiring treatment with systemic steroids.'}], 'secondaryOutcomes': [{'measure': '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.', 'timeFrame': 'one year', 'description': "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."}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['humoral dysfunction', 'humoral immune function'], 'conditions': ['COPD Exacerbation Acute']}, 'referencesModule': {'references': [{'pmid': '20486821', 'type': 'BACKGROUND', 'citation': 'Toy EL, Gallagher KF, Stanley EL, Swensen AR, Duh MS. The economic impact of exacerbations of chronic obstructive pulmonary disease and exacerbation definition: a review. COPD. 2010 Jun;7(3):214-28. doi: 10.3109/15412555.2010.481697.'}, {'pmid': '34592394', 'type': 'BACKGROUND', 'citation': 'Petrov AA, Adatia A, Jolles S, Nair P, Azar A, Walter JE. Antibody Deficiency, Chronic Lung Disease, and Comorbid Conditions: A Case-Based Approach. J Allergy Clin Immunol Pract. 2021 Nov;9(11):3899-3908. doi: 10.1016/j.jaip.2021.09.031. Epub 2021 Sep 28.'}, {'pmid': '19038881', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '20513910', 'type': 'BACKGROUND', 'citation': 'Sethi S. Infection as a comorbidity of COPD. Eur Respir J. 2010 Jun;35(6):1209-15. doi: 10.1183/09031936.00081409.'}, {'pmid': '21864166', 'type': 'BACKGROUND', 'citation': 'Albert RK, Connett J, Bailey WC, Casaburi R, Cooper JA Jr, Criner GJ, Curtis JL, Dransfield MT, Han MK, Lazarus SC, Make B, Marchetti N, Martinez FJ, Madinger NE, McEvoy C, Niewoehner DE, Porsasz J, Price CS, Reilly J, Scanlon PD, Sciurba FC, Scharf SM, Washko GR, Woodruff PG, Anthonisen NR; COPD Clinical Research Network. Azithromycin for prevention of exacerbations of COPD. N Engl J Med. 2011 Aug 25;365(8):689-98. doi: 10.1056/NEJMoa1104623.'}, {'pmid': '29649230', 'type': 'BACKGROUND', 'citation': "Putcha N, Paul GG, Azar A, Wise RA, O'Neal WK, Dransfield MT, Woodruff PG, Curtis JL, Comellas AP, Drummond MB, Lambert AA, Paulin LM, Fawzy A, Kanner RE, Paine R 3rd, Han MK, Martinez FJ, Bowler RP, Barr RG, Hansel NN; SPIROMICS investigators. Lower serum IgA is associated with COPD exacerbation risk in SPIROMICS. PLoS One. 2018 Apr 12;13(4):e0194924. doi: 10.1371/journal.pone.0194924. eCollection 2018."}, {'pmid': '28212436', 'type': 'BACKGROUND', 'citation': 'McCullagh BN, Comellas AP, Ballas ZK, Newell JD Jr, Zimmerman MB, Azar AE. Antibody deficiency in patients with frequent exacerbations of Chronic Obstructive Pulmonary Disease (COPD). PLoS One. 2017 Feb 17;12(2):e0172437. doi: 10.1371/journal.pone.0172437. eCollection 2017.'}, {'pmid': '32368026', 'type': 'BACKGROUND', 'citation': 'Holm AM, Andreassen SL, Christensen VL, Kongerud J, Almas O, Auraen H, Henriksen AH, Aaberge IS, Klingenberg O, Rustoen T. Hypogammaglobulinemia and Risk of Exacerbation and Mortality in Patients with COPD. Int J Chron Obstruct Pulmon Dis. 2020 Apr 16;15:799-807. doi: 10.2147/COPD.S236656. eCollection 2020.'}, {'pmid': '32112921', 'type': 'BACKGROUND', 'citation': 'Traister RS, Coffey K, Xie M, Van Meerbeke S, Pilewski JM, Sorensen RU, Petrov AA. Evaluation of humoral immunity in end-stage lung disease. J Allergy Clin Immunol Pract. 2020 Jun;8(6):2104-2106. doi: 10.1016/j.jaip.2020.01.063. Epub 2020 Feb 26. No abstract available.'}, {'pmid': '24836125', 'type': 'BACKGROUND', 'citation': 'Criner GJ, Connett JE, Aaron SD, Albert RK, Bailey WC, Casaburi R, Cooper JA Jr, Curtis JL, Dransfield MT, Han MK, Make B, Marchetti N, Martinez FJ, Niewoehner DE, Scanlon PD, Sciurba FC, Scharf SM, Sin DD, Voelker H, Washko GR, Woodruff PG, Lazarus SC; COPD Clinical Research Network; Canadian Institutes of Health Research. Simvastatin for the prevention of exacerbations in moderate-to-severe COPD. N Engl J Med. 2014 Jun 5;370(23):2201-10. doi: 10.1056/NEJMoa1403086. Epub 2014 May 18.'}, {'pmid': '29444682', 'type': 'BACKGROUND', 'citation': 'Leitao Filho FS, Ra SW, Mattman A, Schellenberg RS, Criner GJ, Woodruff PG, Lazarus SC, Albert R, Connett JE, Han MK, Martinez FJ, Leung JM, Paul Man SF, Aaron SD, Reed RM, Sin DD; Canadian Respiratory Research Network (CRRN). Serum IgG subclass levels and risk of exacerbations and hospitalizations in patients with COPD. Respir Res. 2018 Feb 14;19(1):30. doi: 10.1186/s12931-018-0733-z.'}, {'pmid': '11048909', 'type': 'BACKGROUND', 'citation': "Barr JT, Schumacher GE, Freeman S, LeMoine M, Bakst AW, Jones PW. American translation, modification, and validation of the St. George's Respiratory Questionnaire. Clin Ther. 2000 Sep;22(9):1121-45. doi: 10.1016/S0149-2918(00)80089-2."}, {'pmid': '16264058', 'type': 'BACKGROUND', 'citation': 'Pellegrino R, Viegi G, Brusasco V, Crapo RO, Burgos F, Casaburi R, Coates A, van der Grinten CP, Gustafsson P, Hankinson J, Jensen R, Johnson DC, MacIntyre N, McKay R, Miller MR, Navajas D, Pedersen OF, Wanger J. Interpretative strategies for lung function tests. Eur Respir J. 2005 Nov;26(5):948-68. doi: 10.1183/09031936.05.00035205. No abstract available.'}, {'pmid': '22935624', 'type': 'BACKGROUND', 'citation': 'Orange JS, Ballow M, Stiehm ER, Ballas ZK, Chinen J, De La Morena M, Kumararatne D, Harville TO, Hesterberg P, Koleilat M, McGhee S, Perez EE, Raasch J, Scherzer R, Schroeder H, Seroogy C, Huissoon A, Sorensen RU, Katial R. Use and interpretation of diagnostic vaccination in primary immunodeficiency: a working group report of the Basic and Clinical Immunology Interest Section of the American Academy of Allergy, Asthma & Immunology. J Allergy Clin Immunol. 2012 Sep;130(3 Suppl):S1-24. doi: 10.1016/j.jaci.2012.07.002.'}, {'pmid': '36435707', 'type': 'BACKGROUND', 'citation': 'Gold MS, Amarasinghe A, Greenhawt M, Kelso JM, Kochhar S, Yu-Hor Thong B, Top KA, Turner PJ, Worm M, Law B. Anaphylaxis: Revision of the Brighton collaboration case definition. Vaccine. 2023 Apr 6;41(15):2605-2614. doi: 10.1016/j.vaccine.2022.11.027. Epub 2022 Nov 24.'}], 'seeAlsoLinks': [{'url': 'http://www.goldcopd.org', 'label': 'Global initiative for Chronic Obstructive Lung Disease'}]}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': '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\n\nGroup #1: SCIgR with Cuvitru 125 mg/kg/week + standard of care management = 20 patients\n\nGroup #2: Standard of care management = 20 patients'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '82 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion criteria:\n\n1. Patients \\> 18 years and ≤ 82 years old.\n2. Patient that meet three (3) or more of the five (5) following criteria.\n\n 1. Dyspnea ≥ 5 on a visual analog scale\n 2. Respiratory rate ≥ 24 breaths per minute\n 3. Heart rate ≥ 95 beats per minute\n 4. Resting SaO2 \\< 92% breathing ambient air of the patient's usual oxygen prescription and/or change in saturation \\> 3% from baseline\n 5. CRP ≥ 10 mg/L\n3. Established diagnosis of COPD with PFTs showing FEV1/FVC \\< 70% or FEV1/VC ratio below the 5th percentile of the predicted value.\\[14\\]\n4. 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.\n5. 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\n6. Medically stable with no acute hospitalizations for non-COPD related events within the last 3 months\n7. Expected life expectancy \\> 1 year\n8. Stable Cardiovascular Disease, with no planned intervention\n9. No history of pulmonary embolism or embolic event\n10. Hepatic function \\< Class B Child-Pugh criteria\n11. Renal insufficiency with eGFR \\> 60 mL/min/1.73m2\n12. No history of DVT or thrombotic events\n13. No history of prior organ transplant\n14. 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.\n15. 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.\n16. Ability to sign informed consent\n\nExclusion criteria:\n\n1. Known history of humoral dysfunction/immunodeficiency\n2. Known hereditary/genetic/congenital defects, and autoimmune disease including hereditary spherocytosis, hereditary elliptocytosis, paroxysmal nocturnal hemoglobinuria, and sickle cell disease\n3. Ongoing or recent therapy with immunoglobulin replacement therapy within the past 6 months\n4. Chronic oral steroid use of prednisone treatment of ≥20 mg daily (or equivalent) will be excluded to ensure subject is medically stable.\n5. Alpha-1 antitrypsin deficiency\n6. Obesity with a BMI \\> 40\n7. Unstable hypertension systolic blood pressure (SBP) \\>160 mmHg upon repeated measure\n8. Diabetes mellitus Type I\n9. Known history of acquired or inherited thrombophilia disorders\n10. Known risk factors of hemolysis, including G6PD deficiency, mitral valve replacement, aortic valve replacement.\n11. Known prolonged periods of immobilization\n12. Known severe hypovolemia noted by SBP ≤ 85 and/or heart rate (HR) \\>130\n13. Known hypercoagulable conditions\n14. Use of estrogens\n15. Indwelling central vascular catheters\n16. Currently actively smoking"}, 'identificationModule': {'nctId': 'NCT05764993', 'briefTitle': 'Prevalence of Humoral Dysfunction in Pts With Frequent Exacerbations of COPD, and the Effect of SCIgR for Prevention', 'organization': {'class': 'OTHER', 'fullName': 'Rochester General Hospital'}, 'officialTitle': 'Prevalence of Humoral Immune Deficiency in Patients With Frequent Exacerbations of COPD, and the Effect of Immunoglobulin Replacement on Future Exacerbations', 'orgStudyIdInfo': {'id': 'IISR Protocol'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Group #1', 'description': 'SCIgR with Cuvitru 125 mg/kg/week + standard of care management', 'interventionNames': ['Biological: CUVITRU - Ig subcutaneous human 20%', 'Other: Standard Medical Therapy']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Group #2', 'description': 'Standard of care management = 20 patients', 'interventionNames': ['Other: Standard Medical Therapy']}], 'interventions': [{'name': 'CUVITRU - Ig subcutaneous human 20%', 'type': 'BIOLOGICAL', 'otherNames': ['Immune Globulin Subcutaneous (Human), 20% Solution'], 'description': 'Subcutaneous Immunoglobin Replacement Therapy, SCigR', 'armGroupLabels': ['Group #1']}, {'name': 'Standard Medical Therapy', 'type': 'OTHER', 'description': 'Standard Medical Therapy', 'armGroupLabels': ['Group #1', 'Group #2']}]}, 'contactsLocationsModule': {'locations': [{'zip': '14607', 'city': 'Rochester', 'state': 'New York', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Dawn Sheflin, RN', 'role': 'CONTACT', 'email': 'Dawn.Sheflin@RochesterRegional.or', 'phone': '585-922-8314'}, {'name': 'Holly Blue, LPN', 'role': 'CONTACT', 'email': 'Holly.Blue@RochesterRegional.org', 'phone': '585-922-8314'}, {'name': 'Syed S Mustafa, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}, {'name': 'Allison Ramsey, MD', 'role': 'SUB_INVESTIGATOR'}, {'name': 'Anne M Holly, PA', 'role': 'SUB_INVESTIGATOR'}, {'name': 'Sara Keller, PA', 'role': 'SUB_INVESTIGATOR'}], 'facility': 'Rochester Regional Health Ctr for Clinical Research - Alexander Park', 'geoPoint': {'lat': 43.15478, 'lon': -77.61556}}, {'zip': '14625', 'city': 'Rochester', 'state': 'New York', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Dawn Sheflin, RN', 'role': 'CONTACT', 'email': 'Dawn.Sheflin@RochesterRegional.org', 'phone': '585-922-8314'}, {'name': 'Holly Blue, LPN', 'role': 'CONTACT', 'email': 'Holly.Blue@RochesterRegional.org', 'phone': '585-922-8314'}, {'name': 'Syed S Mustafa, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}, {'name': 'Allison Ramsey, MD', 'role': 'SUB_INVESTIGATOR'}, {'name': 'Anne M Holly, PA', 'role': 'SUB_INVESTIGATOR'}, {'name': 'Sara Keller, PA', 'role': 'SUB_INVESTIGATOR'}], 'facility': 'Rochester Regional Health - Ctr for Clinical Research - Linden Oaks', 'geoPoint': {'lat': 43.15478, 'lon': -77.61556}}, {'zip': '14626', 'city': 'Rochester', 'state': 'New York', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Dawn Sheflin, RN', 'role': 'CONTACT', 'email': 'Dawn.Sheflin@RochesterRegional.org', 'phone': '585-922-8314'}, {'name': 'Holly Blue, LPN', 'role': 'CONTACT', 'email': 'Holly.Blue@RochesterRegional.org', 'phone': '585-922-8314'}, {'name': 'Syed S Mustafa, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}, {'name': 'Allison Ramsey, MD', 'role': 'SUB_INVESTIGATOR'}, {'name': 'Anne M Holly, PA', 'role': 'SUB_INVESTIGATOR'}, {'name': 'Sara Keller, PA', 'role': 'SUB_INVESTIGATOR'}], 'facility': 'Rochester Regional Health - Ctr for Clinical Research - Greece', 'geoPoint': {'lat': 43.15478, 'lon': -77.61556}}], 'centralContacts': [{'name': 'Dawn Sheflin, RN', 'role': 'CONTACT', 'email': 'Dawn.Sheflin@RochesterRegional.org', 'phone': '585-922-8314'}, {'name': 'Holly Blue, LPN', 'role': 'CONTACT', 'email': 'Holly.Blue@RochesterRegional.org', 'phone': '585-922-8314'}], 'overallOfficials': [{'name': 'Syed S Mustafa, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Rochester General Hospital'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Rochester General Hospital', 'class': 'OTHER'}, 'collaborators': [{'name': 'Takeda', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Principle Investigator', 'investigatorFullName': 'S. Shahzad Mustafa', 'investigatorAffiliation': 'Rochester General Hospital'}}}}