RG-RV for Cat Allergy

(VMR Trial)

Overseen By Lisa Sweeney, RN

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: The University of Texas Medical Branch, Galveston

Must be taking: ICS, albuterol

Must not be taking: Antihistamines, montelukast

Disqualifiers: Pregnancy, Immunosuppressed, BMI > 35, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 1

75 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a treatment called Research Grade RG-RV (Research Grade Rhinovirus 16) affects the airways of people allergic to cats, including those with allergic rhinitis (sneezing and runny nose) and asthma. Researchers will compare these effects in three groups: healthy individuals, people with cat allergies causing sneezing and congestion, and those with cat allergies who also have asthma. Participants should have a cat allergy and either experience frequent sneezing or have mild to moderate asthma. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial requires that participants in the Healthy Control and Allergic Rhinitis groups stop taking inhaled corticosteroids, leukotriene modifiers, or antihistamines for respiratory diseases. Participants in the Allergic Asthma group can continue using inhaled corticosteroids, montelukast, and rescue albuterol or LABAs, but not other respiratory medications.

Is there any evidence suggesting that RG-RV16 is likely to be safe for humans?

Research has shown that rhinovirus type 16 (RV16) is linked to cold-like symptoms, but studies have used it without major safety issues. One study found that RV16 did not worsen cold symptoms in people with allergic rhinitis, a condition where the immune system overreacts to allergens like pollen or pet dander. This suggests the virus is generally well-tolerated, even by those with allergies.

Another study examined people with asthma and found that RV infections often trigger asthma attacks. However, these studies focused more on understanding the virus's effects rather than testing RV16's safety.

Overall, while these studies highlight the effects of RV16, they do not report serious safety concerns. Participants should feel reassured that researchers have studied the treatment in humans before. However, since this is ongoing research, potential volunteers should discuss any concerns with the trial team. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cat allergy?

Unlike the standard treatments for cat allergies, which often include antihistamines and corticosteroids that mainly manage symptoms, RG-RV is unique because it targets the root cause by potentially modifying the immune system's response to allergens. Researchers are excited about this treatment's novel approach—using Research Grade RG-RV to potentially desensitize individuals to cat allergens. This could offer longer-lasting relief and reduce reliance on daily medications. Additionally, if effective, RG-RV might provide a new option for individuals with allergic rhinitis and allergic asthma, offering a more comprehensive solution than current therapies.

What evidence suggests that RG-RV16 could be an effective treatment for cat allergy?

Research has shown that RG-RV16, a modified version of a common cold virus, might help with cat allergies by affecting airway function. Earlier studies found that this virus worsened allergic reactions in the airways, suggesting it can alter how allergies impact breathing. This trial will test RG-RV16 in different groups, including those with allergic rhinitis and allergic asthma, to explore its potential to change airway behavior. This effect might help researchers learn how to control or lessen these reactions in people with cat allergies. While this specific treatment is still under investigation, its potential is promising for those with allergic rhinitis or asthma caused by cat dander. ^{6 7 8 9 10}

Who Is on the Research Team?

William J. Calhoun, MD

Principal Investigator

University of Texas

Are You a Good Fit for This Trial?

This trial is for healthy adults, allergic rhinitis sufferers, and mild-moderate asthmatics aged 18-60 with cat dander allergy. Participants must be non-smokers or long-term ex-smokers without serious respiratory diseases, diabetes, cardiovascular disease, or immune system issues. Pregnant women and those unable to follow the protocol are excluded.

Inclusion Criteria

People who are healthy and not part of the patient group being studied.

I am either male or female.

Subject must be able to understand and provide informed consent

Exclusion Criteria

Healthy Group Normal Group: Inability or unwillingness of a participant to comply with study protocol, Currently taking inhaled corticosteroids, leukotriene modifier, or antihistamines for respiratory disease, Neutralizing Ab to RV16 greater than or equal to 1:8, Pregnant or breastfeeding women or a woman who has a planned pregnancy during the course of the study. Menstruating females must have a negative pregnancy test at the screening visit. Pregnancy testing may be conducted prior to procedures as well at various times in the study, Subjects with household or close contacts who are pregnant or planning a pregnancy during the main subject's participation, who have chronic respiratory disease, who are children under the age of 2 years, or who are adults over 60 years of age or are Immunosuppressed e.g. post-chemotherapy, HIV, Subjects who provide healthcare services or work with elderly or children (e.g. daycare provider, senior citizen care giver).

Allergic Rhinitis Group: Inability or unwillingness of a participant to comply with study protocol, Currently using inhaled steroids, or oral montelukast for respiratory disease, Neutralizing Ab to RV16 greater than or equal to 1:8, Pregnant or breastfeeding women or a woman who has a planned pregnancy during the course of the study. Menstruating females must have a negative pregnancy test at screening visit. Pregnancy testing may be conducted prior to procedures as well at various times in the study, Subjects with household or close contacts who are pregnant or planning a pregnancy during the main subject's participation, who have chronic respiratory disease, who are children under the age of 2 years, or who are adults over 60 years of age or are Immunosuppressed e.g. post-chemotherapy, HIV, Subjects who provide healthcare services or work with elderly or children (e.g. daycare provider, senior citizen care giver), Subjects who have received immunosuppressive treatment within the last 12 months, BMI is greater than 35, History of symptoms consistent with a viral URI within the past 21 days, Results of the CBC do not show clinically important abnormalities, Family history or medical history of liver disease or bleeding disorders, Have not received systemic corticosteroids for 3months prior to Screening, Antiplatelet agents other than aspirin, Subjects who have a positive COVID-19 test will be excluded for 8 weeks.

This criterion excludes people who: - Don't follow the study rules - Take certain respiratory medications - Have specific test results related to their lung function - Had a recent asthma flare-up - Take high doses of certain medications - Are pregnant, planning to get pregnant, or have close contacts who are pregnant - Have certain medical conditions or age groups - Work in healthcare or with children - Had certain treatments or health conditions in the past year - Have a high body mass index (BMI) - Had certain symptoms or medical history - Haven't taken steroid pills for 3 months - Have a certain score on an asthma test - Take certain blood-thinning medications - Tested positive for COVID-19 recently

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Intervention

Participants receive RG-RV16 inoculation to evaluate effects on airway mucosal gene expression and airway remodeling

Immediate and up to 7 days

Multiple visits (in-person) for inoculation and immediate assessments

Follow-up

Participants are monitored for safety and effectiveness after inoculation, including assessments of URI cold symptoms

7 days

Follow-up assessments (in-person and virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Research Grade RG-RV

Trial Overview The study tests RG-RV16's impact on airway genes and remodeling in three groups: healthy individuals (HC), people with allergic rhinitis (AR), and asthmatics (AA) - all sensitive to cat dander. It involves clinical history review, lung function tests, blood work for allergies and antibodies against RV16.

How Is the Trial Designed?

Group I: Healthy Active Control 1 Intervention

Subjects without asthma, COPD, rhinitis and with negative allergen test

Group II: Allergic Rhinitis Active Control 1 Intervention

Subjects without asthma, COPD and with positive allergen test

Group III: Allergic Ashthma Active Control 1 Intervention

Subjects with asthma and positive allergen test

Who Is Running the Clinical Trial?

The University of Texas Medical Branch, Galveston

Lead Sponsor

Trials

263

Recruited

55,400+

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator

Trials

3,361

Recruited

5,516,000+

Mohammad Zaidan, MD

Collaborator

Trials

1

Recruited

80+

Published Research Related to This Trial

Immunotherapy for allergies, such as hay fever and asthma caused by specific allergens like ragweed and dust mites, has been shown to effectively relieve symptoms in controlled studies, with improvements linked to the specific allergen and dosage used.

The treatment leads to significant immunological changes, including increased IgG antibodies and decreased IgE antibodies, but symptoms may return within six months to a year after stopping the injections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy--state of the art. Norman, PS.[2019]

Out of 90 human rhinovirus serotypes tested, only RV type 17 produced significant antigenic variants when exposed to homologous polyclonal antisera, indicating that immunologic pressure can lead to the emergence of new virus variants.

Some of the newly identified variants showed a dramatic 500-fold difference in their ability to be neutralized by the original RV-17 antiserum, suggesting that these variants could evade immune detection and potentially impact vaccine development and treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyper-antigenic variation occurs with human rhinovirus type 17. Patterson, LJ., Hamparian, VV.[2020]

Vaccinating cats with the Fel-CuMV vaccine significantly reduces allergic symptoms in their human owners, as shown in a study involving 10 cat-allergic participants living with 13 vaccinated cats.

The study demonstrated that petting time before allergic symptoms occurred increased after vaccination, and both organ-specific and general symptom scores showed a persistent reduction in allergy symptoms, indicating the vaccine's potential long-term efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunization of Cats against Fel d 1 Results in Reduced Allergic Symptoms of Owners. Thoms, F., Haas, S., Erhart, A., et al.[2021]

A study involving 84 adult cat allergy patients identified multiple significant cat allergens, with rFel d 1 being the most recognized (97.2% of patients), but also highlighted the importance of rFel d 3, rFel d 4, and rFel d 7, which were recognized by over 50% of patients.

The cumulative levels of IgE specific to various cat allergens correlated with the severity of symptoms, suggesting that measuring these levels could help identify patients with more complex cat allergy phenotypes and guide the development of targeted immunotherapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular Allergen-Specific IgE Recognition Profiles and Cumulative Specific IgE Levels Associated with Phenotypes of Cat Allergy. Riabova, K., Karsonova, AV., van Hage, M., et al.[2022]

In a double-blind study involving 39 patients with ragweed hay fever, a 4% disodium cromoglycate (DSCG) nasal solution was found to be no more effective than a placebo in alleviating rhinitis symptoms or reducing the need for other allergy medications.

However, patients with the highest levels of ragweed-specific IgE experienced some symptom relief with DSCG during peak pollen season, although overall, the treatment was deemed relatively ineffective for seasonal allergic rhinitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of ragweed hay fever with intranasally administered disodium cromoglycate. Craig, S., Rubinstein, E., Reisman, RE., et al.[2019]

In a study involving 22 subjects with allergic rhinitis or asthma, rhinovirus (RV16) infection led to increased levels of immune markers G-CSF and IL-8, which were associated with higher neutrophil counts in both blood and nasal secretions, indicating a strong immune response.

The balance of T-helper cell type 1 (Th1) and Th2 cytokines in the airways during RV infection may influence the severity of cold symptoms and the duration of the viral infection, suggesting that individual immune responses play a crucial role in determining the outcome of RV infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relationship of upper and lower airway cytokines to outcome of experimental rhinovirus infection. Gern, JE., Vrtis, R., Grindle, KA., et al.[2007]

The chapter provides detailed methods for producing and standardizing human rhinovirus A1B for use in mouse models, which is crucial for studying the virus's role in respiratory conditions like asthma.

It also outlines techniques for coupling rhinovirus infections with allergen exposure, allowing researchers to investigate the combined effects of viral infections and allergens on respiratory health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modeling Asthma in Mice Using Rhinovirus Infection. Bentley, JK.[2022]

Children with asthma have significantly higher levels of antibodies against rhinovirus species A and C compared to healthy children, indicating a stronger immune response to these viruses in asthmatic individuals.

Despite higher antibody levels in children with asthma, there is no evidence that these antibodies provide protection against rhinovirus infections, suggesting a compromised immune response in asthma that may lead to increased susceptibility to respiratory issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rhinovirus Species-Specific Antibodies Differentially Reflect Clinical Outcomes in Health and Asthma. Megremis, S., Niespodziana, K., Cabauatan, C., et al.[2021]

In a study of 48 allergic rhinitis patients undergoing specific immunotherapy (SIT), levels of TGF-beta and IL-10 were found to be lower than those in healthy individuals, indicating a potential immune response alteration due to the therapy.

The level of IL-17 was initially higher in allergic rhinitis patients but decreased over the two years of SIT, suggesting that monitoring these cytokines could help evaluate the effectiveness of the treatment, particularly after two years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Role of TGF-beta, IL-10 and IL-17 in allergic rhinitis patients with specific immunotherapy]. Lu, HG., Qiu, QH., Lu, C., et al.[2019]

In a study involving 31 volunteers (18 with allergic rhinitis and 13 controls), it was found that allergic individuals experienced significantly greater changes in lower airway response to histamine during rhinovirus (RV) infection compared to non-allergic individuals, indicating that allergy is a risk factor for enhanced airway effects during RV infections.

The severity of the airway response to RV infection was also influenced by baseline lung function, suggesting that factors like initial lung capacity (FEV1) and sensitivity to histamine (PD20) play a role in how severely individuals are affected by the virus, particularly in those with asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rhinovirus infection preferentially increases lower airway responsiveness in allergic subjects. Gern, JE., Calhoun, W., Swenson, C., et al.[2015]

The study identified 41 nearly complete genome sequences of human rhinovirus (RV) isolates from the recently discovered RV-C species, which are linked to asthma and wheezing in infants.

These sequences represent 21 different RV-C genotypes, highlighting the genetic diversity of this virus and its potential role in respiratory illnesses in young children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genome sequences of rhinovirus C isolates from wisconsin pediatric respiratory studies. Liggett, SB., Bochkov, YA., Pappas, T., et al.[2021]

Mouse models of rhinovirus infection showed that strong IgG antibody responses were generated against the RV capsid protein VP1, indicating a potential target for vaccine development.

Two or more infections were necessary to produce detectable neutralizing antibodies and IgA responses, suggesting that a robust immune response may require multiple exposures to the virus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rhinovirus infections and immunisation induce cross-serotype reactive antibodies to VP1. McLean, GR., Walton, RP., Shetty, S., et al.[2022]

Human rhinoviruses are a major cause of upper respiratory infections, but understanding their pathogenesis is challenging due to limitations in animal models, as only chimpanzees and gibbons are naturally susceptible to these viruses.

To study the immune response to rhinoviruses, researchers are using human epithelial cell lines and primary cultures, which help reveal both local and systemic immune responses, making them essential for exploring mechanisms of RV-induced asthma and potential new therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cellular and animals models for rhinovirus infection in asthma. Xatzipsalti, M., Papadopoulos, NG.[2019]

Citations

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RG-RV for Cat Allergy (VMR Trial) Trial Overview The study tests RG-RV16's impact on airway genes and remodeling in three groups: healthy individuals (HC), people with allergic rhinitis (AR), ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC330045/

A common cold virus, rhinovirus 16, potentiates airway ... We conclude that rhinovirus upper respiratory infection significantly augments immediate and late allergic responses in the airways of allergic individuals ...

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NCT02388997 | Treatment With Omalizumab to Improve ... Population surveys have shown a positive correlation between increased levels of total serum immunoglobulin E (IgE) and bronchial hyperreactivity.

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Experimental rhinovirus 16 infection causes variable ... However, it has not been investigated whether rhinovirus infection can induce variable airway obstruction in asthma. We examined the effect of experimental ...

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A Common Cold Virus, Rhinovirus 16, Potentiates Airway ... Many patients with asthma have increased wheezing with colds. We hypothesized that rhinovirus colds might increase asthma by augmenting airway allergic ...

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Characteristics of upper respiratory tract rhinovirus in ... Our study revealed high human rhinovirus (HRV) detection rate in children with allergic rhinitis (AR), and HRV infection (A, B, or C species) is positively ...

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Rhinoviruses, allergic inflammation, and asthma - PMC Summary: Viral infections affect wheezing and asthma in children and adults of all ages. In infancy, wheezing illnesses are usually viral in origin, ...

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Rhinovirus-16 Colds in Healthy and in Asthmatic Subjects Rhinovirus (RV) infections appear to precipitate most asthma exacerbations. To investigate whether RV-16 induces different inflammatory ...

9. jacionline.org jacionline.org/article/S0091-6749(00)80015-9/fulltext

Effects of allergic inflammation of the nasal mucosa on ... Conclusion: In subjects with allergic rhinitis, augmented nasal allergic inflammation before inoculation with RV type 16 does not worsen the severity of cold ...

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Association between asthma and IgG levels specific for ... The aim of this study was to analyze the association between RSV- and RV-specific IgG levels considered as surrogate markers for virus exposure, ...