Clinical trial NCT01866306: A Study to Evaluate the Safety and Use of Human Rhinovirus in Healthy and Asthmatic Participants (MK-0000-218)
Official title: A Dose-Finding and Longitudinal Biomarker Study of Rhinovirus Challenge in Healthy Volunteers and Mild-Moderate Asthmatics to Evaluate the Safety and Use of a Human Rhinovirus Preparation in Developing High Dimensionality Phenotypes ("Handprints") for Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Asthma
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
Collaborators: name: U-BIOPRED Consortium
First posted: 2013-05-31
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: The purpose of this study is to establish the safety and tolerability of Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) human rhinovirus 16 (RV16UB) in healthy and asthmatic participants, and to identify an appropriate dosage of RV16UB in order to study biomarkers in asthmatic participants. The study is divided into 2 parts. Part 1 is a dose-finding study where healthy participants, and asthmatic participants, who were either treated or not treated with a class of long-acting beta antagonists (LABA) will be recruited to undergo nasal challenge with increasing doses of RV16UB. Part 2 is a biomarker study where mild to moderate asthmatics undergo challenge with the most appropriate dose of RV16UB identified in Part 1, based on tolerability and viral effects. .


Eligibility criteria: Inclusion Criteria:

Parts 1 and 2:

* have a Body Mass Index (BMI) between =\< 35 kg/m\^2 and \> 17 kg/m\^2
* female of childbearing potential is not pregnant and agrees to use 2 acceptable methods of birth control until 10 days after the last visit,; or female is of non-childbearing potential
* is a non-smoker, or has not smoked within prior 12 months, with a history of =\< 10 pack-years

Part 1:

Either of the following:

* healthy (may have out-of season seasonal allergies)
* mild to moderate-asthmatic with a history of spontaneous or exertional wheezing; and with all of the following for \> 4 weeks prior: daytime symptoms twice weekly or less, no activity limitation, no nocturnal symptoms, uses reliever treatment twice daily or less, with an unchanged asthma medication dose, and uses inhaled corticosteroid (ICS) at a stable dose-equivalent of =\< 500 mcg/day fluticasone propionate

Part 2:

* mild to moderate-asthmatics only with a history of spontaneous or exertional wheezing; and with all of the following for \> 4 weeks prior: daytime symptoms twice weekly or less, no activity limitation, no nocturnal symptoms, uses reliever treatment twice daily or less, with an unchanged asthma medication dose, and uses ICS at a stable dose-equivalent of =\< 500 mcg/day fluticasone propionate
* had a mild change in symptoms associated with viral syndrome, leading to temporarily increased short acting beta agonist use or increased ICS dose within the past 5 years

Exclusion Criteria:

* has a history of severe or difficult to manage allergies (e.g. food, drug, latex)
* has a history of asthma-related ventilatory failure in adolescence or adulthood
* is positive for hepatitis B surface antigen, hepatitis C antibodies or human immunodeficiency virus (HIV)
* has significant nasal septum deviation, nasal polyps or other nasal anatomical abnormality
* shares the same household or has intimate contact with an infant, pregnant or lactating woman, or immunosuppressed individual
* has a history or current evidence of any upper or lower respiratory tract infection within 6 weeks prior to baseline assessment
* had major surgery or lost 1 unit (500 mL) of blood within prior 4 weeks
* has participated in another investigational trial within the prior 10 weeks
* is pregnant or a nursing mother
* uses excluded prescription or non-prescription medications within 2 weeks prior to initial viral challenge and throughout the trial

Primary outcomes:
measure: Number of Healthy and Asthmatic Participants With Events of Clinical Interest (ECI) (Part 1)
timeFrame: Up to Day 24
measure: Number of Participants With Serious Adverse Events (SAE) (Parts 1 and 2)
timeFrame: Up to Day 24
measure: Number of Asthmatic Participants Treated With a Viral Dose of 100 TCID50 With Challenge Induced Upper Airway Symptoms (Part 1)
timeFrame: Day 1 up to Day 7
measure: Time -Weighted Average (TWA) Percent Change From Baseline (CFB) in Morning FEV1 in Asthmatic Participants on Days 1-7 (Part 2)
timeFrame: Baseline and Days 1 - 7
measure: TWA Percent CFB in Evening FEV1 in Asthmatic Participants on Days 1-7 (Part 2)
timeFrame: Baseline and Days 1- 7
measure: Change From Baseline in Mean Maximum Jackson Cold Symptom Score (CSS) on Days 1 to 14 in Asthmatic Participants (Part 1)
timeFrame: Baseline and Days 1 - 14
measure: Number of Asthmatic Participants Demonstrating at Least 10^3 Copies/ml of Viral RNA in Nasal Lavage Fluid on Days 1 to 14 (Part 1)
timeFrame: Days 1 - 14
Secondary outcomes:
measure: Mean Percent Change From Baseline in Maximum Drop FEV1 of Asthmatic Participants (Part 2)
timeFrame: Baseline and up to day 7
measure: Mean Change From Baseline in TWA Asthma Control Diary (ACD) Score of Asthmatic Participants on Days 3 to 10 (Part 2)
timeFrame: Baseline and Days 3 to 10
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: