Assessment of QBKPN Site-Specific Immunomodulator Efficacy in Improving Innate Immune Function & Reducing Respiratory Tract Infection Morbidity in Older Adults

Study Overview
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Brief Summary
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This study is designed to test whether QBKPN SSI can improve immune function in older adults, including how well it can protect against respiratory and other infections, whether it improves the body's response to COVID-19 vaccines and what effect it has on maintaining or improving quality of life, activity level and health status. QBKPN is a new medication in a class known as Site-Specific Immunomodulators (SSI). SSIs are designed to train and/or improve innate immune function to reduce the risk of infections, improve immune response to cancer, and slow the progression of chronic inflammatory diseases. It is believed that QBKPN SSI can work with the immune system to help protect against respiratory and other infections.

Detailed Description
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This is a randomized, double-blind, placebo-controlled study of adults 65 years of age or older residing in the community, in long-term care (LTC), independent-living or assisted-living facilities to assess the effect of QBKPN SSI on improvement of innate immunity and reduction of all-cause respiratory tract infection morbidity. Approximately 72 participants will be enrolled; approximately 36 from the community and independent-living facilities and approximately 36 from assisted-living and LTC facilities. Eligible participants will be screened and enrolled in the study by visiting study staff, who will conduct all study visits, administer study treatment and perform blood/sample collections. Participants will receive study treatment for 16 weeks then be monitored for 36 weeks post-study treatment with follow-up study visits and blood sampling performed. Immunological testing for Natural Killer (NK) cell function, anti-viral innate immunity and trained innate immunity will be performed. Safety and tolerability of study treatment will be measured with change in clinical laboratory parameters. Clinical benefits of study treatment will be assessed via medical record review and patient-reported outcomes. Study staff will record any confirmed/probable/possible infections (viral and bacterial, including respiratory and non-respiratory), any microbiologic or radiologic testing performed to investigate for infection, any prescribed antibiotics/antivirals and duration of treatment and reason for and duration of any hospitalizations. Clinical assessments will also include frailty index (Rockwood Clinical Frailty Scale), quality of life [Dementia Quality of Life Questionnaire(DEMQOL)] and end-of-life prediction score (CHESS Scale.)

Official Title
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Assessment of QBKPN Site-Specific Immunomodulator (SSI) Efficacy in Improving Innate Immune Function and Reducing All-Cause Respiratory Tract Infection Morbidity in Adults 65 Years of Age of Older Residing in Independent-Living, Assisted-Living and Long-term Care Facilities

Conditions
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Immune Deficiency

Intervention / Treatment
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* Biological: QBKPN SSI
* Other: Normal Saline Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be a resident of the community or a long-term care, independent-living or assisted living facility participating in the study Be aged 65 years or older Be able to provide written, informed consent themselves Male subjects engaged in vaginal intercourse with women of childbearing potential must be surgically sterile or agree to practice effective barrier contraception during the entire study treatment period (16 weeks) and one month after the last dose of study drug or agree to completely abstain from vaginal intercourse with women of childbearing potential during this period. Exclusion Criteria: Life expectancy of less than 3 months due to terminal illness as determined by the Study Investigator Taking biologic immunosuppressive agents (e.g., Anti-Tumour Necrosis Factor Alpha (anti-TNFa) antibodies, rituximab, ibrutinib, imatinib) calcineurin inhibitors, myelosuppressants (e.g., methotrexate, mycophenolate), or other systemic immunosuppressants. Note: NSAIDs, colchicine, aspirin and oral glucocorticoids at a dose equivalent to less than or equal to 5mg prednisone per day are allowed Currently being treated or less than 30 days from being treated for confirmed or probable infection with systemic (i.e., not topical) antibiotics or antivirals Have a known allergy or hypersensitivity to killed whole-cell bacterial vaccines Any condition that, in the opinion of the Investigator, would preclude the person from participation in the study due to safety or monitoring concerns Any treatment with experimental or investigational therapies within 3 months prior to Screening and/or any planned treatment with experimental or investigational therapies during the entire course of study participation On current treatment for active malignancies (e.g., chemotherapy, radiation) or planned cancer surgery during the study period. Note: People on exclusively hormonal therapy for breast or prostate cancer are allowed. People with prior or planned surgery for localized squamous cell or basal cell carcinoma of the skin are allowed

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A randomized, double-blind, placebo-controlled trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: QBKPN SSI<br>QBKPN SSI (0.1 mL) by subcutaneous injection 3 times per week (Monday, Wednesday & Friday) for 16 weeks | Biological: QBKPN SSI<br>* Site-Specific Immunomodulator<br>|
| Placebo Comparator: Placebo<br>Placebo (Normal Saline) (0.1 mL) by subcutaneous injection 3 times per week (Monday, Wednesday & Friday) for 16 weeks | Other: Normal Saline Placebo<br>* Normal Saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Natural Killer (NK) cell function measured by stimulated Interferon Gamma (IFN-y) production using the NK Vue® assay (https://www.nkmax.com/eng/bbs/content.php?co_id=nkvuekit) in patients treated with QBKPN SSI compared to placebo | NK cell function measured by stimulated Interferon Gamma (IFN-y) production using the NK Vue assay | Baseline to Week 16 | 
| Incidence of treatment-emergent adverse events (safety & tolerability) in participants treated with QBKPN SSI compared to placebo | Treatment-emergent adverse events assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 | Baseline to Week 26 | 
| Change in clinical laboratory parameters (safety & tolerability) measured by blood hematology analysis in participants treated with QBKPN SSI compared to placebo | Hematology analysis includes: Hematocrit (Hct), Hemoglobin (Hgb), Mean Corpuscular Hemoglobin (MCH), Mean Corpuscular Hemoglobin Concentration (MCHC), Mean Corpuscular Volume (MCV), platelet count, Red Blood Cell (RBC) count, White Blood Cell (WBC) count with differential | Baseline to Week 26 | 
| Change in clinical laboratory parameters (safety & tolerability) measured by blood chemistry analysis in participants treated with QBKPN SSI compared to placebo | Clinical chemistry analysis includes: Alanine Aminotransferase (ALT), Albumin (ALB), Alkaline Phosphatase (ALK-P), Aspartate Aminotransferase (AST), bilirubin, Gamma-Glutamyl Transferase (GGT), creatinine, estimated Glomerular Filtration Rate (eGFR), C-Reactive Protein (CRP), electrolytes | Baseline to Week 26 | 
| Change in clinical laboratory parameters (safety & tolerability) measured by urinalysis in participants treated wtih QBKPN SSI compared to placebo | Urinalysis includes: blood, glucose, ketones, leukocyte esterase, nitrite, pH and specific gravity | Baseline to Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Demonstrate innate immune training by measuring change in stimulated Interleukin-1 beta (IL-1B) and Granulocyte-macrophage Colony Stimulating Factor (GM-CSF) in participants treated with QBKPN SSI compared to placebo | IL-1B and GM-CSF measured using RBM Myriad's Toll-like Receptor 4 (TLR4) ligand Lipopolysaccharide (LPS) TruCulture Tube Assay | Baseline to Week 16 | 
| Evaluate capacity for anti-viral innate immune response by measuring change in stimulated type I and type III interferon production in participants treated with QBKPN SSI compared to placebo | Type I and type III interferon production measured using RBM Myriad's Toll-like Receptor 7/8 (TLR7/8) agonist (Resiquimod R848) TruCulture Tube assay | Baseline to Week 16 | 
| Difference in incidence of all-cause respiratory tract infections assessed by medical record review in participants treated with QBKPN SSI compared to placebo | Respiratory tract infections identified using revised McGeer Criteria and/or as determined by participants' medical providers | Baseline to Week 16 | 
| Difference in incidence of all-cause respiratory tract infections assessed by patient reported outcomes (PROs) in participants treated with QBKPN SSI compared to placebo | Respiratory tract infections identified using revised McGeer Criteria and/or as determined by participants' medical providers | Baseline to Week 16 | 
| Difference in severity of all-cause respiratory tract infections assessed by medical record review in participants treated with QBKPN SSI compared to placebo | Severity of all-cause respiratory tract infections measured using World Health Organization (WHO) 8-point ordinal scale for respiratory viral infections [minimum score 0 (uninfected) to maximum score 8 (death)] and Pneumonia Severity Index (PORT Score) (minimum: Class I, 0.1% mortality to maximum: Class V, 27% mortality) for respiratory bacterial infections. [Note: if source of infection is unknown, both WHO 8-point ordinal scale and PORT score will be collected.] | Baseline to Week 16 | 
| Difference in severity of all-cause respiratory tract infections assessed by PROs in participants treated with QBKPN SSI compared to placebo | Severity of all-cause respiratory tract infections measured using World Health Organization (WHO) 8-point ordinal scale for respiratory viral infections and Pneumonia Severity Index (PORT Score) for respiratory bacterial infections. [Note: if source of infection is unknown, both WHO 8-point ordinal scale and PORT score will be collected.] | Baseline to Week 16 | 
| Difference in symptom duration of all-cause respiratory tract infections assessed by medical record review in participants treated with QBKPN SSI compared to placebo | Symptom duration assessed by medical record review | Baseline to Week 16 | 
| Difference in symptom duration of all-cause respiratory tract infections assessed by PROs in participants treated with QBKPN SSI compared to placebo | Symptom duration assessed by PROs | Baseline to Week 16 | 
| Number of courses of antibiotic/antiviral drugs prescribed for respiratory infections assessed by medical record review in participants treated with QBKPN SSI compared to placebo | Number of courses of antibiotic/antiviral drugs assessed by medical record review | up to 52 weeks after first dose of study drug | 
| Number of courses of antibiotic/antiviral drugs prescribed for respiratory infections assessed by PROs in participants treated with QBKPN SSI compared to placebo | Number of courses of antibiotic/antiviral drugs assessed by PROs | up to 52 weeks after first dose of study drug | 
| Difference in incidence of all-cause non-respiratory infection assessed by medical record review in participants treated with QBKPN SSI compared to placebo | All-cause non-respiratory infection identified using revised McGeer Criteria and/or as determined by participants' medical providers | Baseline to Week 16 | 
| Difference in incidence of all-cause non-respiratory infection assessed by PROs in participants treated with QBKPN SSI compared to placebo | All-cause non-respiratory infection identified using revised McGeer Criteria and/or as determined by participants' medical providers | Baseline to Week 16 | 
| Difference in severity of all-cause non-respiratory infection assessed by medical record review in participants treated with QBKPN SSI compared to placebo | Severity of all-cause non-respiratory infection assessed by medical record review | Baseline to Week 16 | 
| Difference in severity of all-cause non-respiratory infection assessed by PROs in participants treated with QBKPN SSI compared to placebo | Severity of all-cause non-respiratory infection assessed by PROs | Baseline to Week 16 | 
| Difference in severity of all-cause non-respiratory infection assessed by hospitalizations due to non-respiratory infections in participants treated with QBKPN SSI compared to placebo | Severity of all-cause non-respiratory infection assessed by hospitalizations due to non-respiratory infections | Baseline to Week 16 | 
| Difference in severity of all-cause non-respiratory infection assessed by mortality due to non-respiratory infections in participants treated with QBKPN SSI compared to placebo | Severity of all-cause non-respiratory infection assessed by mortality due to non-respiratory infections | Baseline to Week 16 | 
| Difference in symptom duration of all-cause non-respiratory infection assessed via medical record review in participants treated with QBKPN SSI compared to placebo | Symptom duration assessed via medical record review | Baseline to Week 16 | 
| Difference in symptom duration of all-cause non-respiratory infection assessed by PROs in participants treated with QBKPN SSI compared to placebo | Symptom duration assessed by PROs | Baseline to Week 16 | 
| Number of courses of antibiotic/antiviral drugs prescribed for non-respiratory infections assessed by medical record review in participants treated with QBKPN SSI compared to placebo | assessed by medical record review | up to 52 weeks after first dose of study drug | 
| Number of courses of antibiotic/antiviral drugs prescribed for non-respiratory infections assessed by PROs | Number of courses of antibiotic/antiviral drugs assessed by PROs | up to 52 weeks after first dose of study drug | 
| Change in quality of life as measured by Dementia Quality of Life (DEMQOL) Scale in participants treated with QBKPN SSI compared to placebo | Quality of life measured using DEMQOL Scale. Scores are from 28 to 112; higher scores indicate better quality of life | Baseline to Weeks 16, 34 & 52 | 
| Change in frailty as measured by the Rockwood Clinical Frailty Scale in participants treated with QBKPN SSI compared to placebo | Frailty measured using Rockwood Clinical Frailty Scale. Scores are from minimum of 1 (very fit) to maximum of 7 (severely frail) | Baseline to Weeks 16, 34 & 52 | 
| Change in end-of-life prediction score as measured by Changes in Health, End-Stage Disease and Signs and Symptoms (CHESS) scale in participants treated with QBKPN SSI compared to placebo | End-of-life prediction score measuring using CHESS scale. Scores are from minimum 0 (no health instability) to 5 (very high health instability) | Baseline to Weeks 16, 34 & 52 | 
| Change in all-cause mortality in participants treated with QBKPN SSI compared to placebo |  | Up to 52 weeks after first dose of study drug | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunosenescence, immunodegeneration, immune dysfunction, older adult