RG-RV for Cat Allergy

(VMR Trial)

Overseen by William J. Calhoun, MD

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This is a mechanistic, controlled, open-label, single-site study to evaluate the effects of RG-RV16 inoculation on airway mucosal gene expression and airway remodeling in 25 healthy controls (HC), in 25 allergic rhinitis subjects (AR) with cat dander allergy, and in 25 allergic asthmatic subjects (AA) with cat dander allergy. Three groups (HC, AR, and AA) will undergo screening to establish clinical history, will undergo pulmonary function testing (spirometry), and will have blood drawn for clinical characterization (IgE, , ImmunoCAP, CBC and differential), and for assessing the presence of existing neutralizing antibody against RV16. Only those who meet criteria will be permitted to continue into the interventional and run-out phases of the study.

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.

What data supports the effectiveness of the RG-RV treatment for cat allergy?

The research on immunotherapy for allergies, like hay fever and asthma, shows that treatments targeting specific allergens can relieve symptoms by altering immune responses. This suggests that a similar approach might be effective for cat allergies, potentially supporting the idea behind the RG-RV treatment. ^{1 2 3 4 5}

Is the RG-RV treatment generally safe for humans?

Research involving rhinovirus (RV) infections, including RG-RV16, shows that it can increase respiratory symptoms, especially in people with allergies or asthma. However, these studies do not specifically address the overall safety of RG-RV in humans, so more research is needed to determine its general safety. ^{6 7 8 9 10}

How is the RG-RV treatment for cat allergy different from other treatments?

RG-RV for cat allergy is unique because it uses a specific type of rhinovirus (a virus that causes the common cold) to potentially modify the immune response, which is different from typical allergy treatments that often involve antihistamines or steroids to manage symptoms. ^{7 9 11 12 13}

Research Team

William J. Calhoun, MD

Principal Investigator

University of Texas

Eligibility Criteria

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

You must be between 18 and 60 years old, able to understand and give permission to take part in the study, and have been diagnosed with allergic rhinitis by a doctor. You can't have a history of asthma, COPD, diabetes, or heart disease. You must have had symptoms of nasal congestion or sneezing or eye irritation caused by allergies in the past year. You also need to have a specific allergy to cats and regular exposure to cat dander.

Criterion: You are between 18 and 60 years old, and you have mild to moderate asthma. You have not smoked much in the past, and you do not have a history of diabetes or heart disease. You also have a specific type of asthma that can be treated with the study medication.

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

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

Trial Timeline

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)

Treatment Details

Interventions

• Research Grade RG-RV (Virus Therapy)

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.

Participant Groups

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+

Dr. Vicente Resto

The University of Texas Medical Branch, Galveston

Chief Medical Officer since 2024

MD from Harvard Medical School

Dr. Jochen Reiser

The University of Texas Medical Branch, Galveston

Chief Executive Officer since 2023

MD, PhD from Ruprecht Karls University of Heidelberg, Germany

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator

Trials

3,361

Recruited

5,516,000+

Dr. Jeanne Marrazzo

National Institute of Allergy and Infectious Diseases (NIAID)

Chief Executive Officer since 2023

MD, MPH

Dr. H. Clifford Lane

National Institute of Allergy and Infectious Diseases (NIAID)

Chief Medical Officer

MD

Mohammad Zaidan, MD

Collaborator

Trials

1

Recruited

80+

Findings from Research

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]

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]

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 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 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 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]

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]

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]

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]

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]

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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Immunization of Cats against Fel d 1 Results in Reduced Allergic Symptoms of Owners. [2021]

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

Immunotherapy--state of the art. [2019]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Molecular Allergen-Specific IgE Recognition Profiles and Cumulative Specific IgE Levels Associated with Phenotypes of Cat Allergy. [2022]

4. China pubmed.ncbi.nlm.nih.gov

[Role of TGF-beta, IL-10 and IL-17 in allergic rhinitis patients with specific immunotherapy]. [2019]

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

Treatment of ragweed hay fever with intranasally administered disodium cromoglycate. [2019]

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

Rhinovirus infection preferentially increases lower airway responsiveness in allergic subjects. [2015]

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

Rhinovirus Species-Specific Antibodies Differentially Reflect Clinical Outcomes in Health and Asthma. [2021]

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

Genome sequences of rhinovirus C isolates from wisconsin pediatric respiratory studies. [2021]

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

Modeling Asthma in Mice Using Rhinovirus Infection. [2022]

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

Relationship of upper and lower airway cytokines to outcome of experimental rhinovirus infection. [2007]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Cellular and animals models for rhinovirus infection in asthma. [2019]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Rhinovirus infections and immunisation induce cross-serotype reactive antibodies to VP1. [2022]

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

Hyper-antigenic variation occurs with human rhinovirus type 17. [2020]