QBKPN for Respiratory Infections

(RESILIENCE Trial)

Overseen By Oksana Korolova, Director, Clinical Operations

Age: 65+

Sex: Any

Trial Phase: Phase 2

Sponsor: Qu Biologics Inc.

Must not be taking: Biologic immunosuppressants, Systemic antibiotics

Disqualifiers: Terminal illness, Active malignancies, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 17

Duration: 4 weeks

72 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new medication called QBKPN SSI, a lung-targeted site-specific immunomodulator, designed to enhance the immune system's ability to combat infections, particularly respiratory ones. Researchers aim to determine if QBKPN SSI can improve vaccine responses, maintain better health, and possibly manage blood sugar levels in older adults. Participants will receive QBKPN SSI or a placebo through injections three times a week for four weeks. This trial suits individuals aged 65 and older who live in the community or specific assisted living facilities and are not on certain immune-suppressing medications. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking certain immunosuppressive drugs or are currently being treated with systemic antibiotics or antivirals. NSAIDs, low-dose aspirin, and certain other medications are allowed.

Is there any evidence suggesting that QBKPN SSI is likely to be safe for humans?

Research has shown that QBKPN SSI is safe and generally well-tolerated. In earlier studies, participants did not experience major side effects. These studies also examined how the treatment interacts with the body's immune system to fight infections and boost immune response. The findings suggest that QBKPN SSI might reduce the risk of infections without causing serious side effects. However, since this treatment is still under investigation, participating in a trial is crucial to fully understand its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about QBKPN SSI for respiratory infections because it offers a novel approach by utilizing a subcutaneous injection of a specialized active ingredient three times a week, which is different from the typical oral or inhaled antibiotics used now. This method could potentially enhance the body's immune response directly where it matters, offering a faster and possibly more effective treatment. Unlike standard antibiotics that often face issues with resistance, QBKPN SSI might provide a new mechanism that sidesteps these problems, promising a fresh avenue for tackling stubborn respiratory infections.

What evidence suggests that QBKPN SSI might be an effective treatment for respiratory infections?

Research shows that QBKPN SSI, which participants in this trial may receive, might strengthen the body's immune system, enhancing its defense against infections. Previous studies have found that Site-Specific Immunomodulators (SSI), like QBKPN, can enhance immune function. This boost could lead to better protection against infections, including those in the lungs. Other research has shown that SSIs can help fight cancers and reduce inflammation in conditions like Crohn's disease and ulcerative colitis. These findings suggest that QBKPN SSI might effectively reduce respiratory infections and improve overall immune response. ^{1 2 3 6 7}

Who Is on the Research Team?

Theodore Steiner, MD FRCPC

Principal Investigator

University of British Columbia

Are You a Good Fit for This Trial?

This trial is for older adults (65+) living in certain care facilities who can consent to the study. They must not be on strong immune-suppressing drugs, have a life expectancy less than 3 months, or be treated recently with antibiotics/antivirals. Men must use contraception if applicable.

Inclusion Criteria

You are a resident of a long-term care, independent-living or assisted living facility participating in the study.

Be a resident of the community or a long-term care, independent-living or assisted living facility participating in the study

I am a man who will use effective contraception or abstain from sex with women who can get pregnant during the study.

Exclusion Criteria

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

Have a known allergy or hypersensitivity to killed whole-cell bacterial vaccines

I am not on current cancer treatment except for hormone therapy or minor skin cancer surgery.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive QBKPN SSI or placebo by subcutaneous injection 3 times per week for 4 weeks

4 weeks

12 visits (in-person or self-administered)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including blood/urine sampling and phone call visits

22 weeks

5 visits (in-person), 1 visit (phone call)

Long-term monitoring

Evaluation of durability of QBKPN SSI beyond end of treatment, including assessment of immune response and infection incidence

Up to 26 weeks after first dose

What Are the Treatments Tested in This Trial?

Interventions

• QBKPN SSI

Trial Overview

The trial tests QBKPN SSI, an immunomodulator aiming to boost innate immunity and protect against respiratory infections in older adults. It's compared with a saline placebo to see if it also enhances responses to COVID-19 vaccines and overall health.

How Is the Trial Designed?

Group I: QBKPN SSI Experimental Treatment 1 Intervention

QBKPN SSI (0.1 mL) by subcutaneous injection 3 times per week (Monday, Wednesday \& Friday) for 4 weeks.

Group II: Placebo Placebo Group 1 Intervention

Placebo (Normal Saline) (0.1 mL) by subcutaneous injection 3 times per week (Monday, Wednesday \& Friday) for 4 weeks.

Who Is Running the Clinical Trial?

Qu Biologics Inc.

Lead Sponsor

Trials

6

Recruited

180+

The National Research Council of Canada Industrial Research Assistance Program

Collaborator

Trials

1

Recruited

70+

Published Research Related to This Trial

Q-1, a novel compound from Miao medicine, effectively reduced symptoms of rheumatoid arthritis (RA) in a rat model by inhibiting the NF-κB signaling pathway, which is crucial for inflammation.

In the study involving collagen-induced arthritis rats, treatment with Q-1 significantly decreased arthritis indices, joint swelling, and levels of inflammatory markers compared to untreated model rats, demonstrating its potential as a therapeutic agent for RA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel Compound Q-1 Alleviates Type II Collagen-Induced Arthritis in Rats through the NF-κB Pathway. Xu, T., Guo, JC., Wu, SS., et al.[2022]

Asthma often coexists with chronic rhinosinusitis with nasal polyps (CRSwNP), and both conditions are driven by type 2 (T2) inflammation, which can lead to more severe disease.

Several targeted biologics, such as omalizumab and dupilumab, have shown clinical efficacy in treating patients with refractory T2 airway inflammation, while no effective targeted treatments have been established for non-type-2 endotypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New insights into the pathophysiology and therapeutic targets of asthma and comorbid chronic rhinosinusitis with or without nasal polyposis. Striz, I., Golebski, K., Strizova, Z., et al.[2023]

Tofacitinib has demonstrated efficacy in phase III trials for rheumatoid arthritis, while fostamatinib and VX-509 showed effectiveness in phase II trials, indicating progress in developing oral small molecule immune modulators.

Safety concerns were noted with tofacitinib, including liver test elevation and neutropenia, but overall, the new oral compounds have a reasonable risk-benefit profile compared to traditional biologic therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel small-molecular therapeutics for rheumatoid arthritis. Fleischmann, R.[2021]

The Invigorating Lung and Kidney Prescription (ILKP) significantly modulates cytokine secretion in response to inflammatory stimuli like Lipopolysaccharide (LPS) and cigarette smoke extract (CSE) in various cell types, indicating its potential therapeutic role in managing inflammation in COPD.

Different components of ILKP target specific pathways: the Activating Blood prescription primarily addresses inflammation, while the Replenishing Lung and Kidney prescription focuses on lipid metabolism and oxidative stress regulation, suggesting a multifaceted approach to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of invigorating lung and kidney prescription and its components on secretion of cytokines induced by CSE and LPS]. Wu, YS., Chen, YL., Li, JS., et al.[2014]

Targeted therapies, including biologics and JAK inhibitors, have revolutionized the treatment of autoimmune and inflammatory diseases like rheumatoid arthritis by effectively targeting specific cytokines and signaling molecules.

These therapies not only address unmet medical needs in autoimmune conditions but also hold promise for treating immune/inflammatory diseases affecting the central nervous system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Recent Perspectives for Targeted Therapies]. Tanaka, Y.[2021]

Qingkailing Injection (QKL) was found to be more effective than ribavirin in treating pneumonia caused by respiratory syncytial virus (RSV) in children, with a higher cure rate and faster relief of fever and cough based on a meta-analysis of 7 randomized clinical trials involving 992 cases.

The treatment with QKL showed a good safety profile, with no reported deaths and only mild adverse events such as skin hypersensitivity and slight liver and kidney function abnormalities, although the results should be interpreted cautiously due to methodological weaknesses in the studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Qingkailing Injection () for Treatment of Children Pneumonia Induced by Respiratory Syncytial Virus: A Meta-Analysis of Randomized Controlled Trials. He, S., Li, WS., Luo, YJ., et al.[2018]

A review of 31 immunomodulatory drugs approved between 1998 and 2017 revealed 372 postmarketing safety-related label modifications, indicating that safety issues are often identified after a drug is on the market, with a median duration of 5 years before these issues are recognized.

The most common safety concerns were related to infections and immunologic phenomena, and drugs approved through expedited pathways had more safety issues compared to those approved through regular processes, highlighting the need for ongoing monitoring of these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Twenty Years of Targeted and Biologic Immunomodulatory Drugs: Postmarketing Modifications of Drug Labels Approved by the US Food and Drug Administration. Berman, J., Yavne, Y., Edel, Y., et al.[2022]

Biological therapies for autoimmune rheumatic diseases, such as rheumatoid arthritis and spondyloarthritides, have improved treatment outcomes but come with potential safety concerns, including risks of infections, infusion reactions, and other serious side effects.

The Brazilian Society of Rheumatology conducted a comprehensive review of safety data over the last two decades, categorizing risks by drug class and providing guidelines for safe use, including considerations for pregnancy and lactation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Safe use of biological therapies for the treatment of rheumatoid arthritis and spondyloarthritides]. Mota, LM., Cruz, BA., Brenol, CV., et al.[2017]

B-cell-targeted biologics have the potential to improve outcomes in systemic lupus erythematosus (SLE) by reducing disease activity and limiting complications from traditional immunosuppressive therapies.

Despite past disappointments with some biologics, recent clinical trials are showing encouraging results, indicating that lessons learned have led to better trial designs and potential advancements in treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting B cells with biologics in systemic lupus erythematosus. La Cava, A.[2021]

Bu-Zhong-Yi-Qi-Tang (BZYQT) significantly reduces neutrophil recruitment and inflammatory mediator expression in a murine model of pulmonary inflammation, suggesting its potential to help manage respiratory diseases exacerbated by viral infections.

The study identified several bioactive components in BZYQT, such as isoliquiritigenin and atractylenolide I, which may contribute to its immunomodulatory effects, providing a pharmacological basis for its use in treating respiratory disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrating network pharmacology and experimental verification to decipher the immunomodulatory effect of Bu-Zhong-Yi-Qi-Tang against poly (I:C)-induced pulmonary inflammation. Hu, L., Yamamoto, M., Chen, J., et al.[2022]

Biologic anti-inflammatory agents, including cytokine antagonists and JAK inhibitors, have transformed the treatment of autoimmune rheumatological conditions by effectively controlling inflammation.

However, these therapies can lead to drug-induced lung diseases, which can be challenging to distinguish from lung issues caused by the autoimmune diseases themselves.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse effects of biologic anti-inflammatory agents on the respiratory system: A review. Joseph, D., Tintinger, GR., Ker, JA., et al.[2021]

Immunomodulatory biologics are effective in treating complex conditions like cancer and autoimmune diseases, but they can cause serious adverse reactions such as infections and cytokine release syndrome.

Current strategies are being developed to predict and reduce these adverse reactions, which is crucial for creating safer immunomodulatory biologics in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Challenges and approaches for the development of safer immunomodulatory biologics. Sathish, JG., Sethu, S., Bielsky, MC., et al.[2022]

Qing-Kai-Ling (QKL) oral liquid significantly alleviated pneumonia symptoms in rats, showing effects comparable to the positive control drug dexamethasone, by reducing inflammation markers like TNF-α and increasing protective factors like SOD.

The study revealed that QKL treatment improved the diversity and richness of intestinal flora, restored beneficial bacterial genera, and influenced metabolites and gene expression related to inflammation, suggesting a mechanism involving the modulation of gut microbiota and host metabolism in combating pneumonia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Qing-Kai-Ling oral liquid alleviated pneumonia via regulation of intestinal flora and metabolites in rats. Chen, H., Li, S., Pan, B., et al.[2023]

There is a lack of clear evidence-based guidelines for prescribing biologic therapy in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD), despite concerns about serious respiratory adverse events linked to anti-TNF agents.

The review highlights the need for a framework to assess disease severity and guide treatment decisions, as well as a research agenda to fill the gaps in knowledge regarding the safety of different biologic agents in RA-ILD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of biologic therapies in RA-associated interstitial lung disease. Jani, M., Hirani, N., Matteson, EL., et al.[2022]

Recent advancements in biologics and small-molecule kinase inhibitors have significantly improved treatment outcomes for rheumatoid arthritis, a chronic autoimmune disease that leads to joint damage and functional loss.

Research has identified key immune pathways, particularly involving cytokines like tumor necrosis factor α and interleukin 6, as critical in the disease's progression, guiding the development of targeted therapies such as JAK inhibitors and B-cell depletion strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pathogenetic insights from the treatment of rheumatoid arthritis. McInnes, IB., Schett, G.[2022]

Citations

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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 ...

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SSI Platform

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sciencedirect.com/science/article/pii/S0969805124000349

Tracking the fate of bacteria-derived site-specific ...

As summarized above, the immune modulatory effects of QBECO and QBKPN have been characterized and have shown broad pre-clinical and clinical efficacy in cancer, ...

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QBKPN SSI is designed to restore and enhance innate immune function, the body's first line of defense against infections and other diseases such as cancer. As ...

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Participant Information and Consent Form

The purpose of this study is to continue to look at the safety of QBKPN SSI and the effect it has on your natural immune function, your body's ...

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Assessment of QBKPN Site-Specific Immunomodulator (SSI) Efficacy in Improving Innate Immune Function and Reducing All-Cause Respiratory Tract Infection ...