Feasibility and Safety of Immunoglobulin (Ig) Treatment in COPD Outpatients With Frequent Exacerbations: Pilot Study 1

NCT03018652 | Completed Phase 2 DMC

• 1 other identifier: IgPRx in AECOPD outpatient
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory disease of the airways, associated with poor health status, functional disability, significant morbidity, and increased risk of death. In Ontario, COPD is the leading cause of hospital admission and readmission, and costs the health system approximately 3 billion dollars annually. Individuals with COPD experience increased 'flare-up's' (acute exacerbations) as their disease worsens, characterized by periods of increased shortness of breath, cough, phlegm production, and weakness. Acute exacerbations of COPD (AECOPD) are most commonly caused by viral or bacterial infections, and often require patients to seek attention at the emergency room or hospital for treatment. Current treatments to prevent COPD exacerbations are only modestly effective. New therapies are needed to improve the quality of life and clinical outcomes for individuals living with COPD. Previous research at our center has shown a favourable effect of an antibody treatment (immunoglobulin) on the frequency of AECOPD, doctor visits, treatments, and hospitalizations for COPD patients. However, rigorous studies with more patients are required to confirm this effect. The investigators propose a clinical trial to evaluate immunoglobulin treatment in outpatients with frequent exacerbations. In this study the investigators will determine if immunoglobulin treatment is feasible, safe, tolerable, and potentially effective in reducing the frequency of acute exacerbations. If this study is feasible and potentially effective, it will inform larger studies to confirm the therapeutic effect of immunoglobulin treatment, and would be a major advance in care of COPD.

Conditions

Chronic Obstructive Pulmonary Disease (COPD)

Keywords

COPD; Ig; IPRAC; outpatient

Outcome Measures

Primary Outcomes (2)

• Recruitment

  Average number of patients being recruited per month. The study meets primary outcome if at least 4 patients can be recruited per month on average.

  52 weeks

• Adherence and protocol compliance

  Number and percentage of recruited patients adhere to the allocated treatment and protocol. The investigators aim to achieve 80% adherence rate which is defined as at least 80% of patients adhere to 80% of allocated treatment and protocol

  104 weeks

Secondary Outcomes (9)

• Number of participants with treatment-related adverse events as assessed by CTCAE

  104 weeks

• Proportion of patients able to complete treatment

  104 weeks

• Efficacy trend: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) rates

  104 weeks

• Efficacy trend: Health status

  104 weeks

• Efficacy trend: Quality of life

  104 weeks

Study Arms (2)

Intervention group

EXPERIMENTAL

IVIG 0.5 g/kg, up to maximum of 80 grams will be given on the day of randomization and then every 4 ± 1 weeks for 44 weeks (Total 48 weeks) n=8

Drug: Intravenous immunoglobulin

Control group

PLACEBO COMPARATOR

Normal saline (0.9% NaCl) 5 mL/kg, up to maximum of 800 mL will be given on the day of randomization (this will match the volume of 0.5g/kg of IVIG product) and then every 4 ± 1 weeks for 44 weeks (Total 48 weeks) n=8

Drug: Normal Saline

Interventions

Intravenous immunoglobulin DRUG

IVIG 0.5 g/kg, up to maximum of 80 grams will be given on the day of randomization and then every 4 ± 1 weeks for 44 weeks (Total 48 weeks)

Intervention group

Normal Saline DRUG

5 mL/kg, up to maximum of 800 mL will be given on the day of randomization (this will match the volume of 0.5g/kg of IVIG product) and then every 4 ± 1 weeks for 44 weeks (Total 48 weeks)

Control group

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients with frequent exacerbations of COPD (clinically dominant COPD in the case of multiple co-morbidities eg. bronchiectasis, interstitial lung disease, congestive heart failure)
• Confirmed diagnosis of COPD (bronchodilator FEV1/FVC ratio \<0.7 on spirometry within previous 12 months)
• Age \>40 years
• \>10 pack year smoking history
• Frequent COPD exacerbations in the previous 12 months before enrollment, defined by one or both of the following:
• Treatment as an outpatient with antibiotics or prednisone (physician diagnosed COPD exacerbation) on 2 previous occasions OR
• One hospitalization for COPD exacerbation (as defined by 2/3 of increased dyspnea, sputum volume, or sputum purulence in patients with known airflow limitation)
• Expected to live \> 12 months

You may not qualify if:

• Known severe hypersensitivity to immunoglobulin or its components (anaphylaxis)
• Active or metastatic malignancy (including chronic lymphocytic leukemia) excluding local skin cancers
• History of hematopoietic stem cell transplant or solid organ transplant
• Current treatment with a biological therapy for other conditions
• Concomitant significant immunodeficiency or use of immunosuppressive treatment (other than for COPD)
• Alpha-1 antitrypsin deficiency (based on enzyme level from bloodwork)
• Significant proteinuria (dipstick proteinuria ≥ 3+ AND known urinary protein loss ≥ 2 g/day or nephrotic syndrome) and/or has a history of acute renal failure and/or severe renal impairment (creatinine more than 2.5 times the upper limit of normal and/or on dialysis)
• IgA deficiency (IgA \<0.1 g/L)
• Immunoglobulin therapy in the last 12 months or on current Ig therapy or have a clinical indication for Ig replacement therapy (www.nacblood.ca/resources/guidelines/IVIG.html)
• Pregnancy

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead

Study Sites (1)

The Ottawa Hospital, General Campus

Ottawa, Ontario, K1J 0J2, Canada

Location

Related Publications (2)

• Cowan J, Mulpuru S, Abdallah SJ, Chopra A, Purssell A, McGuinty M, Alvarez GG, Giulivi A, Corrales-Medina V, MacFadden D, Boyle L, Hasimja D, Thavorn K, Mallick R, Aaron SD, Cameron DW. A Randomized Double-Blind Placebo-Control Feasibility Trial of Immunoglobulin Treatment for Prevention of Recurrent Acute Exacerbations of COPD. Int J Chron Obstruct Pulmon Dis. 2021 Dec 3;16:3275-3284. doi: 10.2147/COPD.S338849. eCollection 2021.

  PMID: 34887657 DERIVED

• Cowan J, Mulpuru S, Aaron S, Alvarez G, Giulivi A, Corrales-Medina V, Thiruganasambandamoorthy V, Thavorn K, Mallick R, Cameron DW. Study protocol: a randomized, double-blind, parallel, two-arm, placebo control trial investigating the feasibility and safety of immunoglobulin treatment in COPD patients for prevention of frequent recurrent exacerbations. Pilot Feasibility Stud. 2018 Aug 11;4:135. doi: 10.1186/s40814-018-0327-z. eCollection 2018.

  PMID: 30116551 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Immunoglobulins, Intravenous; Saline Solution

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2016
• First Posted: January 12, 2017
• Study Start: March 11, 2018
• Primary Completion: November 20, 2019
• Study Completion: November 20, 2019
• Last Updated: November 26, 2019

Record last verified: 2019-11

Locations

CA (1)