Clinical Response to Rhinovirus Challenge

NCT02910401 | Completed Phase 2 Results DMC

• 2 other identifiers: 191571U01AI123337
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

Rhinovirus (RV) infections represent the most common cause of asthma exacerbations in children and adolescents. The investigators hypothesize that the immune responses generated in the nose of allergic rhinitics and asthmatics underlie subsequent systemic modulation of the immune system, and that - in susceptible individuals (i.e., those with pre-existing asthma) - this modified nasal milieu is responsible for the asthma exacerbation. Open label single center study in asthmatics as well as allergic rhinitis (AR) and healthy controls. All subjects will undergo good manufacturing practice (GMP) RV16 inoculation and responses will be compared between the 3 cohorts.

Conditions

Asthma; Allergic Rhinitis

Outcome Measures

Primary Outcomes (1)

• Change in Symptom Scores Induced by the Rhinovirus Using Jackson Criteria Including Nasal Congestion, Drainage, Cough, Wheezing

  Jackson criteria subjective score for: nasal secretion (0 - none; 1 - mild; 2 - moderate; 3 - severe), congestion (0 - none; 1 - mild; 2 - moderate; 3 - severe), cough (0 - none; 1 - mild; 2 - moderate; 3 - severe), pain/pressure (0 - none; 1 - mild; 2 - moderate; 3 - severe). Scoring was done twice a day and total score reported for a maximum range for each day of 0-24. Scoring was done daily for 4 weeks.

  Change in symptom score from day 0 to day 4 after inoculation with the rhinovirus

Study Arms (3)

Asthmatic

ACTIVE COMPARATOR

Asthmatic subjects will be infected with Rhinovirus (GMP RV16 human (H)RV-16)

Biological: Rhinovirus (GMP RV16 HRV-16)

Allergic rhinitis

ACTIVE COMPARATOR

Allergic rhinitis subjects will be infected with Rhinovirus (GMP RV16 HRV-16)

Biological: Rhinovirus (GMP RV16 HRV-16)

Healthy control

ACTIVE COMPARATOR

Healthy controls will be infected with Rhinovirus (GMP RV16 HRV-16)

Biological: Rhinovirus (GMP RV16 HRV-16)

Interventions

Rhinovirus (GMP RV16 HRV-16) BIOLOGICAL

300 tissue culture infectious dose (TCID)50 mg/ml intranasal one time only

Allergic rhinitis; Asthmatic; Healthy control

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• All subjects:
• Subjects must be able to understand and provide written informed consent.
• Age 18 to ≤40 years of age, any gender, any racial/ethnic origin
• Female subjects of childbearing potential must have a negative pregnancy test upon study entry (day -7) and before each procedure involving pharmacologic interventions (days 0, 4, and 7).
• Female (and male) subjects with reproductive potential, must agree to use FDA approved methods of birth control for the duration of the study such as, but not limited to, birth control pills, contraceptive foam, diaphragm, IUD, abstinence, or condoms.
• Participants must be willing to comply with study procedures and requirements.
• Negative test for serum neutralizing antibody to RV16 at enrollment visit (\<1:8) (Visit 1).
• Allergic Rhinitis Subjects:
• Allergy as determined by ≥1 positive prick skin test (wheal ≥5 mm diameter and 3mm larger than the diluent control) to Virginia inhalant panel within 5 years, and a history of symptoms of sneezing, rhinorrhea, pruritus, nasal congestion, and/or allergic conjunctivitis on natural exposure to relevant allergens.
• Negative methacholine challenge (less than 20% decline in functional expiratory volume in 1 second (FEV1) at ≤8mg/ml) within 1 year
• FEV1 ≥80% predicted, FEV1/FVC ≥80%.
• No history of wheezing with viral infection in the last 6 years, and no use of rescue inhalers or long-term controllers for asthma in the last 6 years.
• Allergic Asthmatic Subjects:
• Allergy as determined by ≥1 positive prick skin test (wheal ≥5 mm diameter and 3mm larger than the diluent control) to Virginia inhalant panel. Subjects are not required to have allergy symptoms at the time of study. Subjects will report history of symptoms of sneezing, rhinorrhea, pruritus, nasal congestion, and/or allergic conjunctivitis on natural exposure to relevant allergens.
• Asthma determined by physician diagnosis and by a positive methacholine challenge (at least 20% fall in FEV1 at a methacholine concentration of ≤8 mg/ml) at screening protocol visit before enrollment (obtained within the past year).

You may not qualify if:

• Positive test for serum neutralizing antibody to RV16 at enrollment visit (≥1:8) (Visit 1).
• Upper airway modified Jackson criteria symptom scores ≥7 at time of inoculation.
• Chronic heart disease including bradycardia, lung diseases other than asthma, or other chronic illnesses including epilepsy, peptic ulcer disease, thyroid disease, urinary tract infection, vagotonia, autoimmune disease, primary or secondary immunodeficiency or any household contacts who are known to be immune deficient. Any medical conditions that could be adversely affected by the administration of cholinergic agent.
• Any use of corticosteroids, leukotriene (LT) modifiers, antihistamines, omalizumab, theophylline, long-acting anti-muscarinic antagonists (LAMAs), long-acting beta-agonists (LABAs), nedocromil, cromolyn use on a daily basis within 4 weeks prior to Visit 1.
• Current use of ß-blockers or cholinesterase inhibitors (for myasthenia gravis).
• ß2-agonist use ≥4 days/week in any week or ≥2 nights/month during the month before Visit 1.
• Recent (within 1-yr) asthma exacerbation requiring urgent care visit (unless the treatment involved only the use of a bronchodilator), hospitalization, or oral CCS
• Intubation or management in the intensive care unit (ICU) for an asthma exacerbation ever.
• An upper or lower respiratory tract infection within 2 months prior to enrollment.
• Previous nasal or sinus surgery within the last 12 months
• \>5 pack-year smoking history or any smoking within the past 6 mos.
• Hemoglobin \<11.5 g/dL for non-African American subjects or hemoglobin \< 11.0 g/dL for African American subjects detected at Visit 1.
• Laboratory values (other than hemoglobin and absolute neutrophil count (ANC)) measured at Visit 1 that are considered to be of clinical relevance by the Investigator.
• Absolute neutrophil count (ANC) \<1500 cells/mm3 (or 1.5 K/µL) or absolute lymphocyte count (ALC) \<800 cells/mm3 detected at Visit 1.
• Use of investigational drugs within 12 weeks of participation

Sponsors & Collaborators

• University of Virginia: lead
• National Institutes of Health (NIH): collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

Related Publications (1)

• Feng X, Lawrence MG, Payne SC, Mattos J, Etter E, Negri JA, Murphy D, Kennedy JL, Steinke JW, Borish L. Lower viral loads in subjects with rhinovirus-challenged allergy despite reduced innate immunity. Ann Allergy Asthma Immunol. 2022 Apr;128(4):414-422.e2. doi: 10.1016/j.anai.2022.01.007. Epub 2022 Jan 12.

  PMID: 35031416 RESULT

MeSH Terms

Conditions

Asthma; Rhinitis, Allergic

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Rhinitis; Nose Diseases; Otorhinolaryngologic Diseases

Results Point of Contact

• Title: Larry Borish, MD
• Organization: University of Virginia

lb4@virginia.edu

4342436570

Study Officials

• Larry Borish, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine and Microbiology

Study Record Dates

• First Submitted: September 8, 2016
• First Posted: September 22, 2016
• Study Start: September 1, 2016
• Primary Completion: September 21, 2022
• Study Completion: September 21, 2022
• Last Updated: January 9, 2024
• Results First Posted: January 9, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)