A Study to Evaluate the Safety and Use of Human Rhinovirus in Healthy and Asthmatic Participants (MK-0000-218)

August 2, 2018 updated by: Merck Sharp & Dohme LLC

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

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. .

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
59

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Healthy 10 TCID50 (Part 1)
Healthy participants were treated with 10 Tissue Culture Infective Dose 50 (TCID50) administered by spraying an atomized viral suspension of RV16UB into a single nostril.
Biological: RV16UB
RV16UB is administered by spraying an atomized viral suspension into a single nostril. Planned doses of RV16UB in Part 1 are 10 Tissue Culture Infective Dose 50 (TCID50), 100 TCID50, 1000 TCID50 and 10,000 TCID50.
Experimental: Healthy 100 TCID50 (Part 1)
Healthy participants were treated with 100 TCID50 administered by spraying an atomized viral suspension of RV16UB into a single nostril.
Biological: RV16UB
RV16UB is administered by spraying an atomized viral suspension into a single nostril. Planned doses of RV16UB in Part 1 are 10 Tissue Culture Infective Dose 50 (TCID50), 100 TCID50, 1000 TCID50 and 10,000 TCID50.
Experimental: Healthy 1000 TCID50 (Part 1)
Healthy participants were treated with 1000 TCID50 administered by spraying an atomized viral suspension of RV16UB into a single nostril.
Biological: RV16UB
RV16UB is administered by spraying an atomized viral suspension into a single nostril. Planned doses of RV16UB in Part 1 are 10 Tissue Culture Infective Dose 50 (TCID50), 100 TCID50, 1000 TCID50 and 10,000 TCID50.
Experimental: Asthmatic non-LABA 10 TCID50 (Part 1)
Participants with mild to moderate asthma, not concomitantly treated with LABA, were treated with 10 TCID50 administered by spraying an atomized viral suspension of RV16UB into a single nostril.
Biological: RV16UB
RV16UB is administered by spraying an atomized viral suspension into a single nostril. Planned doses of RV16UB in Part 1 are 10 Tissue Culture Infective Dose 50 (TCID50), 100 TCID50, 1000 TCID50 and 10,000 TCID50.
Experimental: Asthmatic non-LABA 100 TCID50 (Part 1)
Participants with mild to moderate asthma, not concomitantly treated with LABA, were treated with 100 TCID50 administered by spraying an atomized viral suspension of RV16UB into a single nostril.
Biological: RV16UB
RV16UB is administered by spraying an atomized viral suspension into a single nostril. Planned doses of RV16UB in Part 1 are 10 Tissue Culture Infective Dose 50 (TCID50), 100 TCID50, 1000 TCID50 and 10,000 TCID50.
Experimental: Asthmatic LABA 100 TCID50 (Part 1)
Participants with mild to moderate asthma, concomitantly treated with LABA, were treated with 100 TCID50 administered by spraying an atomized viral suspension of RV16UB into a single nostril.
Biological: RV16UB
RV16UB is administered by spraying an atomized viral suspension into a single nostril. Planned doses of RV16UB in Part 1 are 10 Tissue Culture Infective Dose 50 (TCID50), 100 TCID50, 1000 TCID50 and 10,000 TCID50.
Drug: LABA
Asthmatic participants were treated with LABA as part of their standard of care
Experimental: Asthmatic non-LABA 100 TCID50 (Part 2)
Participants with mild to moderate asthma, not concomitantly treated with LABA, were treated with 100 TCID50 administered by spraying an atomized viral suspension of RV16UB into a single nostril.
Biological: RV16UB
RV16UB is administered by spraying an atomized viral suspension into a single nostril. Planned doses of RV16UB in Part 1 are 10 Tissue Culture Infective Dose 50 (TCID50), 100 TCID50, 1000 TCID50 and 10,000 TCID50.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Healthy and Asthmatic Participants With Events of Clinical Interest (ECI) (Part 1)
Time Frame: Up to Day 24
ECI are selected non-serious and serious adverse events which include the following: an overdose of Sponsor's product; requirement for systemic steroids to treat asthma exacerbation related to virus challenge; acute reaction to virus challenge, confirmed through repeat measurement and when considered potentially associated with administration of virus; specified vital sign findings within 4hr of challenge; specified symptom findings within 24hr of challenge; >20% decrease in Forced Expiratory Volume in 1 second (FEV1) relative to baseline within 4hr of challenge; dyspnea associated with drop in FEV1 (within 4hr of challenge) that is unresponsive to a bronchodilator rescue agent within 20 minutes; Grade 2+ deviation from normal values of liver-related laboratory parameters at any time between challenge and day 14.
Up to Day 24
Number of Participants With Serious Adverse Events (SAE) (Parts 1 and 2)
Time Frame: Up to Day 24
A SAE is any adverse event occurring at any dose or during any use of the Sponsor's product that: results in death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing in-patient hospitalization; is a congenital anomaly/birth defect; is a cancer; is associated with an overdose; is another important medical event.
Up to Day 24
Number of Asthmatic Participants Treated With a Viral Dose of 100 TCID50 With Challenge Induced Upper Airway Symptoms (Part 1)
Time Frame: Day 1 up to Day 7
Asthmatic participants from Part 1 were treated with RV16UB virus at a dose of 100 TCID50, and challenge induced upper airway symptoms were monitored with a diary recording Jackson Cold Symptom Score (CSS). The CSS measures 8 cold symptoms, with each symptom scored from 0 (absent) to 3 (severe). The total score ranges from 0-24, with higher scores reflecting greater severity. The number of participants with a CSS score equal or greater than 3 for two days in a row are presented.
Day 1 up to Day 7
Time -Weighted Average (TWA) Percent Change From Baseline (CFB) in Morning FEV1 in Asthmatic Participants on Days 1-7 (Part 2)
Time Frame: Baseline and Days 1 - 7
Log-transformed FEV1 data were fit by Bayesian hierarchical longitudinal models, with a random participant effect and a fixed categorical effect for day. All baseline (day -7 to day -1) FEV1 were assumed to be with equal mean. FEV1 assessments obtained between 3 am to 3 pm were counted as morning measurements. The TWA CFB morning FEV1 on days 1-7 was calculated as the difference of the mean of estimated day 1-7 morning FEV1 value and the corresponding estimated baseline value. The 95% Confidence Interval actually refers to a 95% Credible Interval. The anticipated mean reduction from baseline is 10%.
Baseline and Days 1 - 7
TWA Percent CFB in Evening FEV1 in Asthmatic Participants on Days 1-7 (Part 2)
Time Frame: Baseline and Days 1- 7
Log-transformed FEV1 data were fit by Bayesian hierarchical longitudinal models, with a random participant effect and a fixed categorical effect for day. All baseline (day -7 to day -1) FEV1 were assumed to be with equal mean. FEV1 assessments obtained between 3 pm to next day 3 am were counted as evening measurements. The TWA CFB evening FEV1 on days 1-7 was calculated as the difference of the mean of estimated day 1-7 evening FEV1 value and the corresponding estimated baseline value. The FEV1 readings on the evenings of sputum inductions were excluded from the analyses. The 95% Confidence Interval actually refers to a 95% Credible Interval. The anticipated mean reduction from baseline is 10%.
Baseline and Days 1- 7
Change From Baseline in Mean Maximum Jackson Cold Symptom Score (CSS) on Days 1 to 14 in Asthmatic Participants (Part 1)
Time Frame: Baseline and Days 1 - 14
Asthmatic participants from Part 1 were treated with RV16UB virus, and challenge induced upper airway symptoms were monitored with a diary recording CSS. The CSS measures 8 cold symptoms, with each symptom scored from 0 (absent) to 3 (severe). The total score ranges from 0-24, with higher scores reflecting greater severity, and a positive change from baseline indicating worsening symptoms.
Baseline and Days 1 - 14
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)
Time Frame: Days 1 - 14
Viral RNA was measured by real time reverse transcriptase polymerase chain reaction (qRT-PCR) from nasal lavage fluid collected on day 3 and day 7 from asthmatic participants, and the number of participants with at least 10^3 copies/ml was determined.
Days 1 - 14

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Mean Percent Change From Baseline in Maximum Drop FEV1 of Asthmatic Participants (Part 2)
Time Frame: Baseline and up to day 7
Log-transformed FEV1 data were fit by Bayesian hierarchical longitudinal models, with a random participant effect and a fixed categorical effect for day. All baseline (day -7 to day -1) FEV1 were assumed to be with equal mean. The FEV1 readings on the evenings of sputum inductions were excluded from the analyses. The percent decrease of the lowest FEV1 measurement after viral challenge compared to the TWA of the baseline FEV1 is presented. The 95% Confidence Interval actually refers to a 95% Credible Interval. The mean percent decrease is anticipated to be different from zero.
Baseline and up to day 7
Mean Change From Baseline in TWA Asthma Control Diary (ACD) Score of Asthmatic Participants on Days 3 to 10 (Part 2)
Time Frame: Baseline and Days 3 to 10
The ACD contains seven symptom questions (nocturnal awakening, waking in the morning with symptoms, activity limitation, shortness of breath and wheezing) which are answered on rising in the morning and retiring at bedtime. Missing scores are imputed by linear interpolation or extrapolation. Daily ACD score was fit by a Bayesian hierarchical longitudinal model with participant-specific intercept and a fixed categorical effect for day. All baseline (day -7 to day -1) ACD scores are assumed to be with equal mean. The ACD score is the sum of responses to the seven questions, with answers on a 7-point scale (0= no impairment; 6 = maximum impairment) with the score ranging from 0 to 42, and higher scores indicating greater impairment. The 95% Confidence Interval actually refers to a 95% Credible Interval. The mean percent increase is anticipated to be different from zero.
Baseline and Days 3 to 10

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Merck Sharp & Dohme LLC

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
U-BIOPRED Consortium

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 22, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 25, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 18, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 28, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 28, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 31, 2013

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 4, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 2, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 0000-218
  • 2013-000618-39 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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