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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Immune Deficiency
• Intervention / Treatment: Biological: QBKPN SSI; Other: Normal Saline Placebo

Detailed Description

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.)

• Study Type: Interventional
• Enrollment (Estimated): 72
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Andrea Cameron, RN MSc CCRP; Phone Number: 41493 604-734-1450; Email: acameron@qubiologics.com
• Study Contact Backup: Name: Hal Gunn, MD; Phone Number: 604-734-1450; Email: hal@qubiologics.com

Study Locations

• Canada
  • British Columbia
    • Burnaby, British Columbia, Canada, V5G 4X4
      • Qu Biologics Trial Site
      • Contact: Andrea Cameron, RN MSc CCRP; Phone Number: 41493 604-734-1450; Email: acameron@qubiologics.com
      • Principal Investigator: Theodore Steiner, MD FRCPC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Be a resident of the community or a long-term care, independent-living or assisted living facility participating in the study
2. Be aged 65 years or older
3. Be able to provide written, informed consent themselves
4. 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:

1. Life expectancy of less than 3 months due to terminal illness as determined by the Study Investigator
2. 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
3. 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
4. Have a known allergy or hypersensitivity to killed whole-cell bacterial vaccines
5. Any condition that, in the opinion of the Investigator, would preclude the person from participation in the study due to safety or monitoring concerns
6. 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
7. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

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 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
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
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
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 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 PROs	Number of courses of antibiotic/antiviral drugs assessed by PROs	up to 52 weeks after first dose of study drug

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Plasma immune biomarkers measured using TruCulture Tube assay (under stimulated and unstimulated conditions) of 48 analytes (cytokines & chemokines) using multiplex technology assessment	Baseline to Weeks 8,16, 26, 34, 42 & 52
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	Adaptive immune response measured by CD4+ and CD8+ T-cell response to SARS-CoV-2 S protein-derived peptides	Baseline to Weeks 16, 34 & 52
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	Adaptive immune response to SARS-CoV-2 vaccination measured by SARS-CoV-2 anti-S antibody titer	Baseline to Weeks 16, 34 & 52
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)	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	Baseline to Weeks 16, 34 & 52
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.	Change in plasma metabolome measured using untargeted mass spectrometry	Baseline to Weeks 16, 34 & 52
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	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	Baseline to Weeks 16 & 52
Evaluation of durability of QBKPN SSI beyond Week 16 in participants treated with QBKPN SSI compared to placebo	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)	Up to 52 weeks after first dose of study drug
Assessment of glycemic control through hemoglobin A1C (HbA1c) in participants treated with QBKPN compared to placebo	Change in HbA1c	Baseline to Weeks 16 & 26

Collaborators and Investigators

• Sponsor: Qu Biologics Inc.
• Collaborators: The National Research Council of Canada Industrial Research Assistance Program
• Investigators: Principal Investigator: Theodore Steiner, MD FRCPC, University of British Columbia

Study record dates

Study Major Dates

• Study Start (Actual): April 11, 2023
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: May 11, 2022
• First Submitted That Met QC Criteria: June 13, 2022
• First Posted (Actual): June 16, 2022

Study Record Updates

• Last Update Posted (Actual): August 21, 2023
• Last Update Submitted That Met QC Criteria: August 16, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Immunosenescence; older adult; immunodegeneration; immune dysfunction
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Diseases; Immune System Diseases; Immunologic Deficiency Syndromes; Respiratory Tract Infections
• Other Study ID Numbers: QBKPN-IS-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No