RESILIENCE: Assessment of QBKPN Site-Specific Immunomodulator Efficacy in Improving Innate Immune Function & Reducing Respiratory Tract Infection Morbidity in Older Adults
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
This is a randomized, double-blind, placebo-controlled study of adults 65 years of age or older residing 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 independent-living or assisted-living facilities and approximately 36 from 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.)
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: QBKPN SSI QBKPN SSI (0.1 mL) by subcutaneous injection 3 times per week (Monday, Wednesday & Friday) for 16 weeks |
Biological: QBKPN SSI
Site-Specific Immunomodulator
|
| Placebo Comparator: Placebo Placebo (Normal Saline) (0.1 mL) by subcutaneous injection 3 times per week (Monday, Wednesday & Friday) for 16 weeks |
Other: Normal Saline Placebo
Normal Saline
|
Outcome Measures
Primary Outcome Measures
- 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 [Baseline to Week 16]
NK cell function measured by stimulated Interferon Gamma (IFN-y) production using the NK Vue assay
- Incidence of treatment-emergent adverse events (safety & tolerability) in participants treated with QBKPN SSI compared to placebo [Baseline to Week 26]
Treatment-emergent adverse events assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0
- Change in clinical laboratory parameters (safety & tolerability) measured by blood hematology analysis in participants treated with QBKPN SSI compared to placebo [Baseline to Week 26]
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
- Change in clinical laboratory parameters (safety & tolerability) measured by blood chemistry analysis in participants treated with QBKPN SSI compared to placebo [Baseline to Week 26]
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
- Change in clinical laboratory parameters (safety & tolerability) measured by urinalysis in participants treated wtih QBKPN SSI compared to placebo [Baseline to Week 26]
Urinalysis includes: blood, glucose, ketones, leukocyte esterase, nitrite, pH and specific gravity
Secondary Outcome Measures
- 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 [Baseline to Week 16]
IL-1B and GM-CSF measured using RBM Myriad's Toll-like Receptor 4 (TLR4) ligand Lipopolysaccharide (LPS) TruCulture Tube Assay
- 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 [Baseline to Week 16]
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
- Difference in incidence of all-cause respiratory tract infections assessed by medical record review in participants treated with QBKPN SSI compared to placebo [Baseline to Week 16]
Respiratory tract infections identified using revised McGeer Criteria and/or as determined by participants' medical providers
- Difference in incidence of all-cause respiratory tract infections assessed by patient reported outcomes (PROs) in participants treated with QBKPN SSI compared to placebo [Baseline to Week 16]
Respiratory tract infections identified using revised McGeer Criteria and/or as determined by participants' medical providers
- Difference in severity of all-cause respiratory tract infections assessed by medical record review in participants treated with QBKPN SSI compared to placebo [Baseline to Week 16]
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
- Difference in severity of all-cause respiratory tract infections assessed by PROs up to Day 60 after diagnosis in participants treated with QBKPN SSI compared to placebo [Baseline to Week 16]
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
- Difference in symptom duration of all-cause respiratory tract infections assessed by medical record review in participants treated with QBKPN SSI compared to placebo [Baseline to Week 16]
Symptom duration assessed by medical record review
- Difference in symptom duration of all-cause respiratory tract infections assessed by PROs up to Day 60 after diagnosis in participants treated with QBKPN SSI compared to placebo [Baseline to Week 16]
Symptom duration assessed by PROs
- 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 [up to 52 weeks after first dose of study drug]
Number of courses of antibiotic/antiviral drugs assessed by medical record review
- Number of courses of antibiotic/antiviral drugs prescribed for respiratory infections assessed by PROs in participants treated with QBKPN SSI compared to placebo [up to 52 weeks after first dose of study drug]
Number of courses of antibiotic/antiviral drugs assessed by PROs
- Difference in incidence of all-cause non-respiratory infection assessed by medical record review in participants treated with QBKPN SSI compared to placebo [Baseline to Week 16]
All-cause non-respiratory infection identified using revised McGeer Criteria and/or as determined by participants' medical providers
- Difference in incidence of all-cause non-respiratory infection assessed by PROs in participants treated with QBKPN SSI compared to placebo [Baseline to Week 16]
All-cause non-respiratory infection identified using revised McGeer Criteria and/or as determined by participants' medical providers
- Difference in severity of all-cause non-respiratory infection assessed by medical record review in participants treated with QBKPN SSI compared to placebo [Baseline to Week 16]
Severity of all-cause non-respiratory infection assessed by medical record review
- Difference in severity of all-cause non-respiratory infection assessed by PROs in participants treated with QBKPN SSI compared to placebo [Baseline to Week 16]
Severity of all-cause non-respiratory infection assessed by PROs
- 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 [Baseline to Week 16]
Severity of all-cause non-respiratory infection assessed by hospitalizations due to non-respiratory infections
- 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 [Baseline to Week 16]
Severity of all-cause non-respiratory infection assessed by mortality due to non-respiratory infections
- Difference in symptom duration of all-cause non-respiratory infection assessed via medical record review in participants treated with QBKPN SSI compared to placebo [Baseline to Week 16]
Symptom duration assessed via medical record review
- Difference in symptom duration of all-cause non-respiratory infection assessed by PROs in participants treated with QBKPN SSI compared to placebo [Baseline to Week 16]
Symptom duration assessed by PROs
- 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 [up to 52 weeks after first dose of study drug]
assessed by medical record review
- Number of courses of antibiotic/antiviral drugs prescribed for non-respiratory infections assessed by PROs up to Day 60 after diagnosis [Baseline to Week 16]
Number of courses of antibiotic/antiviral drugs assessed by PROs up to Day 60 after diagnosis
- Change in quality of life as measured by Dementia Quality of Life (DEMQOL) Scale in participants treated with QBKPN SSI compared to placebo [Baseline to Weeks 16, 34 & 52]
Quality of life measured using DEMQOL Scale. Scores are from 28 to 112; higher scores indicate better quality of life
- Change in frailty as measured by the Rockwood Clinical Frailty Scale in participants treated with QBKPN SSI compared to placebo [Baseline to Weeks 16, 34 & 52]
Frailty measured using Rockwood Clinical Frailty Scale. Scores are from minimum of 1 (very fit) to maximum of 7 (severely frail)
- 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 [Baseline to Weeks 16, 34 & 52]
End-of-life prediction score measuring using CHESS scale. Scores are from minimum 0 (no health instability) to 5 (very high health instability)
- Change in all-cause mortality in participants treated with QBKPN SSI compared to placebo [Up to 52 weeks after first dose of study drug]
Other Outcome Measures
- Change in additional measures of plasma immune biomarkers that regulate innate & adaptive immune function augmentation measured using TruCulture Tube® assay (under stimulated & unstimulated conditions) of 48 analytes (cytokines & chemokines) [Baseline to Weeks 8,16, 26, 34, 42 & 52]
Plasma immune biomarkers measured using TruCulture Tube assay (under stimulated and unstimulated conditions) of 48 analytes (cytokines & chemokines) using multiplex technology assessment
- Evaluation of duration of adaptive immune response to SARS-CoV-2 vaccination measured by change in Cluster of Differentiation 4+ (CD4+) and Cluster of Differentiation 8+ (CD8+) T-cell response to SARS-CoV-2 S protein-derived peptides [Baseline to Weeks 16, 34 & 52]
Adaptive immune response measured by CD4+ and CD8+ T-cell response to SARS-CoV-2 S protein-derived peptides
- Evaluation of duration of adaptive immune response to SARS-CoV-2 vaccination measured by change in SARS-CoV-2 anti-S antibody titer in participants treated with QBKPN SSI compared to placebo [Baseline to Weeks 16, 34 & 52]
Adaptive immune response to SARS-CoV-2 vaccination measured by SARS-CoV-2 anti-S antibody titer
- Evaluation of duration of adaptive immune response to SARS-CoV-2 vaccination measured by change in SARS-CoV-2 anti-S antibody secretion from antigen stimulated Peripheral Blood Mononuclear Cells (PBMCs) [Baseline to Weeks 16, 34 & 52]
Adaptive immune response to SARS-CoV-2 vaccination measured by SARS-CoV-2 anti-S antibody secretion from antigen stimulated Peripheral Blood Mononuclear Cells (PBMCs) in participants treated with QBKPN versus placebo
- Change in plasma metabolome measured using mass spectrometry (untargeted) to assess which metabolites are significantly changed by treatment and which may predict response to treatment in patients treated with QBKPN SSI compared to placebo. [Baseline to Weeks 16, 34 & 52]
Change in plasma metabolome measured using untargeted mass spectrometry
- Assessment of correlation of Immunoglobulin G (IgG) antibodies to K.variicola with the NK cell function and innate immune training in participants treated with QBKPN SSI compared to placebo [Baseline to Weeks 16 & 52]
Correlation assessed by quantification of IgG antibodies to K. variicola and correlation with NK Vue assay and RBM Myriad's TLR4 ligand (LPS) TruCulture Tube assay results
- Evaluation of durability of QBKPN SSI beyond Week 16 in participants treated with QBKPN SSI compared to placebo [Up to 52 weeks after first dose of study drug]
Durability of QBKPN SSI assessed by measuring NK cell function (see Outcome #1), innate immune training (see Outcome #4), anti-viral innate immunity (see Outcome #5), all-cause respiratory and non-respiratory infections (see Outcomes #6 to #11)
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Be a resident of 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 period and one month after the last dose of study drug or agree to completely abstain from vaginal intercourse with women of childbearing potential during their participation in the study
Exclusion Criteria:
-
Life expectancy of less than 3 months due to terminal illness as determined by the Principal or Sub-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 antibiotics/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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Qu Biologics Trial Site | Burnaby | British Columbia | Canada | V5G 4X4 |
Sponsors and Collaborators
- Qu Biologics Inc.
- The National Research Council of Canada Industrial Research Assistance Program
Investigators
- Principal Investigator: Theodore Steiner, MD FRCPC, University of British Columbia
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- QBKPN-IS-01