Study of Airway Inflammatory Responses to Experimental Rhinovirus Infection

NCT03508479 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: 16-3283
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to characterize in detail the clinical, physiologic, and inflammatory features of Human Rhinovirus (HRV) infection in healthy volunteers without underlying lung disease while also evaluating the safety of HRV administrations.

Conditions

Healthy Volunteers; Rhinovirus

Outcome Measures

Primary Outcomes (1)

• Change in neutrophils/mL in nasal lavage fluid from baseline to mean of days 2-4 post inoculation

  Nasal lavage fluid will be collected at baseline. Participants will then undergo RG-HRV16 inoculation. Nasal lavage fluid will be collected on days 2-3 post inoculation and mean neutrophils/ml over days 2-4 will be compared to baseline.

  Baseline and study visit days 2-4

Secondary Outcomes (3)

• Mean Symptom Score from Cold Symptom Questionnaire up to 4 weeks post-inoculation

  4 weeks post-inoculation

• Change in FEV1 and FEF25-75% from baseline to 4 weeks post-inoculation

  Baseline and 4 weeks post-inoculation

• Change in Methacholine reactivity, as measured by the concentration of methacholine resulting in a 20% drop in FEV1 (PC20), from baseline to day 4 post-inoculation

  Baseline and study visit day 4 (post-inoculation)

Study Arms (1)

RG-HRV16 Inoculation

EXPERIMENTAL

While wearing a dental bib, subjects will be asked to blow the nose prior to inoculation. With the head tilted back, a total of 0.5 mL (0.25 mL/nostril) will be administered using the MAD Nasal™ Intranasal Mucosal Atomization Device. Subjects instructed not to blow nose for 30 minutes afterwards.

Biological: RG-HRV16

Interventions

RG-HRV16 BIOLOGICAL

0.25 mL inoculum intranasally delivered into each nostril (0.5 mL total delivered). Total cumulative dose of 1000 median tissue culture infective dose at 50% of cells inoculated (TCID50).

Also known as: Rhinovirus Type 16

RG-HRV16 Inoculation

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18-45 years of either gender
• Non-smoker (less than 10 cigarettes per month for at least the prior 3 years)
• Negative pregnancy test (for females as applicable)
• Oxygen saturation of \> 94% and blood pressure with systolic value between 140-90 mm Hg and diastolic between 80-55 mm Hg
• Willingness to hold all nasal medications (including, but not limited to, nasal steroids or nasal spray decongestants), oral antihistamines and leukotriene inhibitors for at least 1 week prior to Day 0 and continuing throughout the remaining study period.
• Negative Allergy Skin Test (AST) at a separate screening visit performed prior to study enrollment, University of North Carolina Institutional Review Board (UNC IRB) approved study # 98-0799, Database and Screening Protocol for Research Studies of the Center for Environmental Medicine and Lung Biology (CEMALB). (Results from AST performed within the past 12 months as part of another study protocol or AST reports from testing performed by the subject's Medical Doctor (MD) within the past 12 months will also be accepted.)
• Negative methacholine inhalation challenge as performed in the separate screening protocol. (Less than a 20% decrease in Forced Exhaled Volume at 1 second (FEV1) at a maximum methacholine concentration of 10 mg/ml).
• Normal lung function, defined as (NHANES III predicted set):
• Forced Vital Capacity (FVC) of ≥ 80 % of that predicted for gender, ethnicity, age and height
• FEV1 of ≥ 80 % of that predicted for gender, ethnicity, age and height
• Ratio of Forced Exhaled Volume at 1 second to Forced Vital Capacity (FEV1/FVC) ≥ .75
• No nasal symptoms, based on respiratory questionnaire

You may not qualify if:

• Presence of neutralizing antibodies to RG-HRV-16 at the screening visit to a titer of ≥ 1:2.
• Inability or unwillingness of a participant to give written informed consent
• History of rhinitis, chronic sinusitis, or other sinus disease, or any chronic cardiorespiratory disease
• Subjects with household contacts with chronic lung disease, who are children under the age of 2 years, and who are adults over the age of 65 years
• Subjects who live in communal settings (i.e. dormitories)
• Respiratory infection (cough, sore throat, sinusitis, fever etc) within prior 4 weeks
• Received any live vaccine in the past 4 weeks or an inactivated vaccine within the past 2 weeks
• Active wheezing at the time of the Day 0 visit
• Pregnancy or nursing or women who are currently trying to become pregnant; all female subjects, except those who have had a hysterectomy with oophorectomy, will undergo urine pregnancy testing on the morning of the screening visit and again on the on Day 0 at the time of arrival to the lab and prior to HRV administration. A positive pregnancy test will exclude the subject
• History of any immunosuppressive disease or a positive Human immunodeficiency virus (HIV) test at the screening visit
• Use of immunosuppressive drugs within the past 6 months
• Chronic medications which, in the opinion of the study physician(s), may either increase the risks of participation or may interfere with the findings of the study
• Current use of beta-adrenergic blocking agents
• Current use of antidepressants if classified as tricyclic or Monoamine oxidase inhibitors (MAO) inhibitors;
• Known hypersensitivity to methacholine or to other parasympathomimetic agents;

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead

Study Sites (1)

UNC Center for Environmental Medicine, Asthma and Lung Biology

Chapel Hill, North Carolina, 27599-7310, United States

Location

Study Officials

• Michelle Hernandez, MD

  University of North Carolina

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2018
• First Posted: April 25, 2018
• Study Start: December 1, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: June 3, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)