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

Trial Summary

What is the purpose of this trial?

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, what effect it has on maintaining or improving quality of life, activity level and health status and whether it has an effect on glycemic control. 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.

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.

What data supports the effectiveness of the drug QBKPN SSI for respiratory infections?

The research on biologic therapies, which are similar to QBKPN SSI, shows that targeting specific immune cells and pathways can improve outcomes in autoimmune diseases like rheumatoid arthritis and systemic lupus erythematosus. These therapies have been effective in reducing inflammation and disease activity, suggesting that QBKPN SSI might also help manage respiratory infections by modulating the immune response. ^{1 2 3 4 5}

Is QBKPN safe for human use?

The safety of immunomodulatory biologics like QBKPN can be a concern due to potential adverse reactions such as infections, allergic reactions, and other immune-related issues. While specific safety data for QBKPN is not available, similar treatments have been associated with these risks, and ongoing research aims to improve their safety. ^{6 7 8 9 10}

What makes the QBKPN treatment unique for respiratory infections?

QBKPN SSI is a novel treatment that targets the lungs specifically to modulate the immune system, which is different from traditional treatments that may not focus on lung-specific immune responses. This targeted approach could potentially offer more effective management of respiratory infections by enhancing the body's natural immune response directly in the lungs. ^{11 12 13 14 15}

Research Team

Theodore Steiner, MD FRCPC

Principal Investigator

University of British Columbia

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. South Africa pubmed.ncbi.nlm.nih.gov

Adverse effects of biologic anti-inflammatory agents on the respiratory system: A review. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Targeting B cells with biologics in systemic lupus erythematosus. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

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

4. Japan pubmed.ncbi.nlm.nih.gov

[Recent Perspectives for Targeted Therapies]. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Pathogenetic insights from the treatment of rheumatoid arthritis. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

The safety of biologic therapies in RA-associated interstitial lung disease. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Challenges and approaches for the development of safer immunomodulatory biologics. [2022]

8. England pubmed.ncbi.nlm.nih.gov

New insights into the pathophysiology and therapeutic targets of asthma and comorbid chronic rhinosinusitis with or without nasal polyposis. [2023]

9. England 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. [2022]

10. Brazil pubmed.ncbi.nlm.nih.gov

[Safe use of biological therapies for the treatment of rheumatoid arthritis and spondyloarthritides]. [2017]

11. China pubmed.ncbi.nlm.nih.gov

Qingkailing Injection () for Treatment of Children Pneumonia Induced by Respiratory Syncytial Virus: A Meta-Analysis of Randomized Controlled Trials. [2018]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Qing-Kai-Ling oral liquid alleviated pneumonia via regulation of intestinal flora and metabolites in rats. [2023]

13. Switzerland 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. [2022]

14. China pubmed.ncbi.nlm.nih.gov

[Effect of invigorating lung and kidney prescription and its components on secretion of cytokines induced by CSE and LPS]. [2014]

15. United States pubmed.ncbi.nlm.nih.gov

Novel Compound Q-1 Alleviates Type II Collagen-Induced Arthritis in Rats through the NF-κB Pathway. [2022]