Healthy VolunteersPhase 1UWI-02NCT01769573

A First-in-Human Safety and Dose-Finding Study of New Type-16 Human Rhinovirus (RG-HRV16) Inoculum in Healthy Volunteers

A Phase 1 study testing RG-HRV16 in people with Healthy Volunteers, run by University of Wisconsin, Madison at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 50 yearsHealthy volunteers can take part
Conditions the study is for: Healthy Volunteers
What is being tested?: RG-HRV16
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 36 participants
Where: 1 siteUnited States
Study dates: Jul 2013to Dec 2017
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 50 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Capable and willing to grant written informed consent (in English) and cooperate with study procedures and requirements including willingness to avoid cold symptom medications during the study.
Age between 18 and 50 years (children and older adults will be excluded from the study due to the possibility of greater morbidity associated with upper respiratory infections in these age groups).
Absence of HRV16 neutralizing antibody.
Safety laboratory assessments within normal University of WI Hospital and Clinics (UWHC) ranges or grade 1 (mild) laboratory abnormalities which are deemed not clinically significant in the judgment of the PI. Labs to include CBC with differential and platelets, BUN, creatinine, AST, ALT and IgA and IgG serum immunoglobulins. Any lymphopenia outside of the normal range will be an absolute exclusion.
Subjects must be willing to refrain from taking nasal decongestants, antihistamines or cough/cold preparations (this includes dietary supplements and homeopathic preparations used specifically for cold/flu e.g., vitamin C, zinc, echinacea) within the 7 days prior to Visit 1 and throughout the study until after the completion of Visit 5.

Who cannot join

A chronic medical condition, which may increase risk or interfere with the conduct of the study, including, but not limited to heart disease, Type I of II diabetes mellitus, asthma, COPD, other chronic lung disease, perennial rhinitis and chronic rhinosinusitis.
Subjects with household 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 50 years of age.
Subjects who provide healthcare services or work with elderly or children (e.g. daycare provider, senior citizen care giver).
Subjects with seasonal allergies will be excluded only if allergy symptoms are present at baseline, or are anticipated to occur during the study period.
Smoking within the past 6 months.
Subjects who have received immunosuppressive treatment within the last 12 months.

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Upper respiratory infection (URI or sinusitis) in the past 4 weeks.
Subjects with a history of a significant adverse reaction or intolerance to a previous live, attenuated vaccine.
Pregnant or breastfeeding women or a woman who has a planned pregnancy during the course of the study.
Unwillingness of study participants to use adequate birth control methods during the course of the study. Adequate birth control methods include oral contraceptives, injections such as Depo-Provera, an intrauterine device or double-barrier contraception (combination of condom and contraceptive sponge or cervical cap and spermicide or another combination approved in writing by the Principal Investigator).

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Wisconsin Hospital and Clinics
Madison, Wisconsin, 53792

Other trials in United States

About this study

This research study will test different doses of RG-HRV16 to find the minimum dose needed to give research subjects cold symptoms of at least moderate intensity. The study will also test the safety of RG-HRV16. This information will be used in future studies (for example, to test antiviral preparations, sprays that could protect from getting a cold or decrease cold symptoms or to understand more about how rhinovirus can lead to asthma worsening). RG-HRV16 is a common cold virus that has been made in a new way and has not been used in humans before.

Read the detailed description

Rhinoviruses are the most frequently cause of the common cold. HRV16 (Family Picornaviridae Genus Rhinovirus type 16) has been used extensively to induce colds in studies of experimentally inoculated volunteers that are designed to study the pathogenesis of colds and effects of antiviral medications.

Experimental inoculation with human rhinovirus type 16 (HRV16) administered intranasally via aerosolization has been used at the University of Wisconsin for over 30 years, and has proven to be a safe tool to reproducibly induce symptomatic colds. HRV has been linked with exacerbations of asthma and COPD, and this model has been used to evaluate inflammatory mechanisms and to test the efficacy of treatments for the common cold. Recent refinements in the technology available to produce and safety test reagents that are intended to be administered to human volunteers as part of research protocols has prompted us to produce a new lot of HRV16 in accordance with standards of current Good Manufacturing Procedures (cGMP). For this inoculum, we have used a cDNA clone (reverse genetics) to generate source virus, thus this new virus inoculum will be referred to as RG-HRV16.

This approach has two main advantages over using viruses isolated from nasal secretions. First, several "new" respiratory viruses (e.g. metapneumovirus, bocavirus, SARS, rhinovirus group C) have been discovered in the past 10 years, and there is little doubt that additional viruses will be discovered. Therefore, it is impossible to ensure that nasal secretions that are chosen for isolation of "seed virus" contain only the pathogen of interest. This problem is minimized through the use of virus derived from a cDNA clone that was produced in E. coli. Second, RNA viruses, such as HRV, mutate as the virus grows because their RNA polymerases have no error-correcting function. The cDNA clone, reproduced by the much more accurate E. coli DNA polymerase, provides a stable source of virus sequence for production of future inocula.

This study represents a first-in-human, phase 1 study to assess the safety of RG-HRV16 in humans and identify the dose needed to produce moderate-to-severe colds in 75% of HRV16-seronegative human volunteers.

Conditions: Healthy Volunteers
Being tested: RG-HRV16, Placebo
Keywords: normal

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

RG-HRV16Biological
Also called Rhinovirus type 16
A suspension of the RG-HRV16 virus in Minimal Essential Media (MEM, HyClone) containing 0.1% Human Serum Albumin
PlaceboDrug
The placebo to be used will be Minimal Essential Media (MEM, HyClone) containing 0.1% Human Serum Albumin. Placebo will be supplied in 2 ml borosilicate glass vials sealed with butyl stoppers containing 0.5 ml.

Study groups in NCT01769573
Study group	Role	What they receive
100 TCID50	Experimental	RG-HRV16 dose of 100 TCID50 administered intranasally (0.25ml per nostril) one time. Receives: Biological: RG-HRV16
1,000 TCID50	Experimental	RG-HRV16 dose of 1,000 TCID50 administered intranasally (0.25ml per nostril) one time. Receives: Biological: RG-HRV16
10,000 TCID50	Experimental	RG-HRV16 dose of 10,000 TCID50 administered intranasally (0.25ml per nostril) one time. Receives: Biological: RG-HRV16
Placebo	Placebo comparator	Diluent administered intranasally (0.25ml per nostril) one time. Receives: Drug: Placebo
500 TCID50	Experimental	RG-HRV16 dose of 500 TCID50 administered intranasally (0.25ml per nostril) one time. Receives: Biological: RG-HRV16

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With Colds With at Least Moderate Intensity
The percentage of colds of at least moderate intensity examined by RG-HRV16 dose; this will be measured by the number of subjects per RG-HRV16 dose group who have maximum weekly cold symptom score of ≥7 out of 39 on the modified Jackson criteria during the first week after inoculation
Measured: 1 week
Frequency of Adverse Events
Safety as determined by the frequency of adverse event reporting examined by RG-HRV16 dose.
Measured: 4 weeks

Secondary outcomes (2)

Mean Cold Symptom Score
The Mean Cold Symptom Score induced by each RG-HRV16 dose and by the placebo inoculation. The scale is called the Jackson Criteria for Cold Symptom Assessment. There are 13 variables of cold symptoms that each participant scores 0 (not present), 1 (mild), 2 (moderate) to 3 (severe), twice per day, once at 8am and once at 8pm. The 13 variables are: cough, nasal discharge, sneezing, stuffy nose, sore throat, headache, malaise, chilliness, shaking chills, fever, laryngitis, aching joints or muscles, and watery/burning eyes. The scores are added up for each time point, with a minimum score of 0 and a max score of 39 per time point. The highest score per day is taken and the highest score over the 7 day period starting from the day of the inoculation and for 7 days is deemed the mean cold symptom score. The higher the score, the more cold symptoms the participant reports and the worse the participant feels.
Measured: 4 weeks
Infection Rate
Infection rate per RG-HRV16 dose as measured by the percentage of individuals in the dosing group with detectable viral shedding.
Measured: 4 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 2013Dec 2017

First posted16 Jan 2013 (estimated)
Study startJul 2013
Primary completionNov 2016
Study completionDec 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Healthy VolunteersStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Other
Allocation: Non-randomised
Intervention model: Single group
Masking: Single blind
Who is masked: Participant
Enrolment: 36 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01769573
Sponsor's protocol ID: 2012-1036
Other IDs: IND15328
Acronym: UWI-02
Status last verified: Feb 2019
First submitted: 14 Jan 2013
Last updated: 3 Jun 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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All Healthy Volunteers trials

Study at a glance

From the registry record, last updated by the sponsor on 3 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A First-in-Human Safety and Dose-Finding Study of New Type-16 Human Rhinovirus (RG-HRV16) Inoculum in Healthy Volunteers
ClinicalTrials.gov ID: NCT01769573
Acronym / sponsor ID: UWI-02 / 2012-1036
Conditions: Healthy Volunteers
Keywords: normal
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 36 participants (actual)
Lead sponsor: University of Wisconsin, MadisonUniversity, hospital or other
Study start: Jul 2013
Primary completion: Nov 2016 (actual)
Study completion: Dec 2017 (actual)
First posted: 16 Jan 2013 (estimated)
Results: Posted 3 Jun 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Other
Allocation: Non-randomised
Intervention model: Single group
Masking: Single blind (participant)
Number of arms: 5

Arm	Type	Receives
100 TCID50	Experimental	Biological: RG-HRV16RG-HRV16 dose of 100 TCID50 administered intranasally (0.25ml per nostril) one time.
1,000 TCID50	Experimental	Biological: RG-HRV16RG-HRV16 dose of 1,000 TCID50 administered intranasally (0.25ml per nostril) one time.
10,000 TCID50	Experimental	Biological: RG-HRV16RG-HRV16 dose of 10,000 TCID50 administered intranasally (0.25ml per nostril) one time.
Placebo	Placebo comparator	Drug: PlaceboDiluent administered intranasally (0.25ml per nostril) one time.
500 TCID50	Experimental	Biological: RG-HRV16RG-HRV16 dose of 500 TCID50 administered intranasally (0.25ml per nostril) one time.

Who may qualify

Ages: 18 to 50 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (5 listed)

Capable and willing to grant written informed consent (in English) and cooperate with study procedures and requirements including willingness to avoid cold symptom medications during the study.
Age between 18 and 50 years (children and older adults will be excluded from the study due to the possibility of greater morbidity associated with upper respiratory infections in these age groups).
Absence of HRV16 neutralizing antibody.
Safety laboratory assessments within normal University of WI Hospital and Clinics (UWHC) ranges or grade 1 (mild) laboratory abnormalities which are deemed not clinically significant in the judgment of the PI. Labs to include CBC with differential and platelets, BUN, creatinine, AST, ALT and IgA and IgG serum immunoglobulins. Any lymphopenia outside of the normal range will be an absolute exclusion.
Subjects must be willing to refrain from taking nasal decongestants, antihistamines or cough/cold preparations (this includes dietary supplements and homeopathic preparations used specifically for cold/flu e.g., vitamin C, zinc, echinacea) within the 7 days prior to Visit 1 and throughout the study until after the completion of Visit 5.

Key exclusion criteria (10 listed)

A chronic medical condition, which may increase risk or interfere with the conduct of the study, including, but not limited to heart disease, Type I of II diabetes mellitus, asthma, COPD, other chronic lung disease, perennial rhinitis and chronic rhinosinusitis.
Subjects with household 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 50 years of age.
Subjects who provide healthcare services or work with elderly or children (e.g. daycare provider, senior citizen care giver).
Subjects with seasonal allergies will be excluded only if allergy symptoms are present at baseline, or are anticipated to occur during the study period.
Smoking within the past 6 months.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
RG-HRV16Also: Rhinovirus type 16A suspension of the RG-HRV16 virus in Minimal Essential Media (MEM, HyClone) containing 0.1% Human Serum Albumin	Biological	1,000 TCID50, 10,000 TCID50, 100 TCID50, 500 TCID50
PlaceboThe placebo to be used will be Minimal Essential Media (MEM, HyClone) containing 0.1% Human Serum Albumin. Placebo will be supplied in 2 ml borosilicate glass vials sealed with butyl stoppers containing 0.5 ml.	Drug	Placebo

Primary outcome

Number of Participants With Colds With at Least Moderate Intensity
Time frame: 1 week
The percentage of colds of at least moderate intensity examined by RG-HRV16 dose; this will be measured by the number of subjects per RG-HRV16 dose group who have maximum weekly cold symptom score of ≥7 out of 39 on the modified Jackson criteria during the first week after inoculation
Frequency of Adverse Events
Time frame: 4 weeks
Safety as determined by the frequency of adverse event reporting examined by RG-HRV16 dose.

2 secondary outcomes

Mean Cold Symptom Score
Time frame: 4 weeks
Infection Rate
Time frame: 4 weeks

Results and safety

Results posted to the registry on 3 Jun 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
100 TCID50	10	10
500 TCID50	6	6
1,000 TCID50	10	10
10,000 TCID50	0	0
Placebo	10	10

Primary outcome: Number of Participants With Colds With at Least Moderate Intensity

Time frame: 1 week. Count of participants. Unit: Participants

Measure	100 TCID50 n = 10	500 TCID50 n = 6	1,000 TCID50 n = 10	10,000 TCID50 n = 0	Placebo n = 10
Value	4	2	7	0	0

Population analysed: The trial completed and met its goal before needing to enroll into the 10,000 TCID50 group.

Primary outcome: Frequency of Adverse Events

Time frame: 4 weeks. Count of participants. Unit: Participants

Measure	100 TCID50 n = 10	500 TCID50 n = 6	1,000 TCID50 n = 10	10,000 TCID50 n = 0	Placebo n = 10
Value	4	1	5	0	3

Population analysed: The trial completed and met its goal before needing to enroll into the 10,000 TCID50 group.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: From date of signed consent until completion of study or roughly 60 days.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
100 TCID50	0 of 10 (0%)	4 of 10 (40%)	0 of 10
500 TCID50	0 of 6 (0%)	1 of 6 (16.7%)	0 of 6
1,000 TCID50	0 of 10 (0%)	5 of 10 (50%)	0 of 10
10,000 TCID50	0 of 0	0 of 0	0
Placebo	0 of 10 (0%)	3 of 10 (30%)	0 of 10

Limitations and caveats (from the sponsor): Limitations include inclusion of healthy adults as study subjects; it is possible that individuals with chronic respiratory disease (e.g. asthma, COPD) could develop milder colds and lower respiratory infections with lower doses of virus.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

James Gern, MD principal investigator

UW Madison

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing RG-HRV16 in people with Healthy Volunteers, run by University of Wisconsin, Madison at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Colds With at Least Moderate Intensity (time frame: 1 week). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01769573.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jun 2019.