InfluenzaPhase 1/2NCT01646138
Influenza A 2009 H1N1 Challenge Study in Healthy Adults
A Phase 1/2 study testing Ca/04/2009/H1N1 Vero Grown Challenge Virus in people with Influenza, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
Background: A challenge study exposes a person to a disease and allows researchers to study the disease through the body's healing process. An influenza challenge study that looks at different amounts of the flu virus can provide more information on the smallest amount needed to cause an infection. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Influenza
- What is being tested?
- Ca/04/2009/H1N1 Vero Grown Challenge Virus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2012to Dec 2013
- Phase
- Phase 1/2
- 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
None listed.
Who cannot join
- Presence of self-reported or medically documented significant medical condition including but not limited to:
- Chronic pulmonary disease (e.g., asthma, emphysema).
- Chronic cardiovascular disease (e.g., cardiomyopathy, congestive heart failure, cardiac surgery, ischemic heart disease, known anatomic defects).
- Chronic medical conditions requiring close medical follow-up or hospitalization during the past 5 years (e.g., diabetes mellitus, renal dysfunction, hemoglobinopathies).
- Immunosuppression or ongoing malignancy.
- Neurological and neurodevelopmental conditions (e.g., cerebral palsy, epilepsy, stroke, seizures).
Show all 36Show fewer
- Postinfectious or postvaccine neurological sequelae.
- Have close or household (i.e., share the same apartment or house) high-risk contacts including but not limited to:
- Persons greater than or equal to 65 years of age.
- Children < 5 years of age.
- Residents of nursing homes.
- Persons of any age with significant chronic medical conditions such as:
- Chronic pulmonary disease (e.g., asthma).
- Chronic cardiovascular disease (e.g., cardiomyopathy, congestive heart failure, cardiac surgery, ischemic heart disease, known anatomic defects).
- Contacts who required medical follow-up or hospitalization during the past 5 years because of chronic metabolic disease (e.g., diabetes mellitus, renal dysfunction, hemoglobinopathies).
- Immunosuppression or cancer.
- Neurological and neurodevelopmental conditions (e.g., cerebral palsy, epilepsy, stroke, seizures).
- Children and teenagers who are receiving long-term aspirin therapy.
- Women who are pregnant or who are trying to become pregnant.
- Individual with body mass index (BMI) less than or equal to 18.5 and greater than or equal to 40.
- Smokes more than 4 cigarettes or other tobacco products on weekly basis.
- Complete blood count (CBC) with differential outside of the NIH Department of Laboratory Medicine (DLM) normal reference range and deemed clinically significant by the PI.
- Chemistries in the acute care, mineral, and/or hepatic panels, and/or any of the following: lactate dehydrogenase, uric acid, creatine kinase, and total protein outside of the NIH DLM normal reference range and deemed clinically significant by the PI.
- Urinalysis outside of the NIH DLM normal reference range and deemed clinically significant by the PI.
- Clinically significant abnormality on electrocardiogram .
- Clinically significant abnormality as deemed by the PI on echocardiographic testing.
- Recent acute illness within 1 week of admission to the isolation facility.
- Known allergy to treatments for influenza (including but not limited to oseltamivir, nonsteroidals).
- Known allergy to 2 or more classes of antibiotics (e.g., penicillins, cephalosporins, fluoroquinolones, or glycopeptides).
- Receipt of blood or blood products (including immunoglobulins) within 3 months prior to enrollment.
- Receipt of any unlicensed drug within 3 months or 5.5 half lives (whichever is greater) prior to enrollment.
- Receipt of any unlicensed vaccine within 6 months prior to enrollment.
- Self-reported or known history of current alcoholism or drug abuse, or positive urine/serum test for drugs of abuse (i.e., amphetamines, cocaine, benzodiazepines, opiates, or metabolites, but not tetrahydrocannabinol(THC) or metabolites).
- Self-reported or known history of psychiatric or psychological issues deemed by the PI to be a contraindication to protocol participation
- Known close contact with anyone known to have influenza in the past 7 days.
- Any condition that, in the judgment of the Principal Investigator, is a contraindication to protocol participation or impairs the volunteer s ability to give informed consent.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Influenza A 2009 H1N1 Human Challenge Study in Healthy Adult Volunteers
Background:
- A challenge study exposes a person to a disease and allows researchers to study the disease through the body's healing process. An influenza challenge study that looks at different amounts of the flu virus can provide more information on the smallest amount needed to cause an infection. Researchers want to give one dose of the Influenza A H1N1 virus to healthy volunteers to see how the body responds to the virus.
Read more
Objectives:
- To find the smallest dose of Influenza A H1N1 virus that may cause a mild to moderate flu infection in a healthy adult.
- To study how the body s immune system responds to the virus.
Eligibility:
- Healthy volunteers at least 18 years of age.
- Participants must be willing to remain in isolation for a minimum of 9 days.
Design:
- Participants will be admitted to a hospital inpatient isolation unit. They will be screened with a physical exam and medical history. They will also have heart and lung function tests. Blood, urine, and nasal swab/wash samples will be collected.
- Participants will receive a single nasal spray of the flu virus. They will stay on the inpatient unit for at least 9 days.
- Participants will be monitored for the length of their stay. They will have frequent blood tests and other procedures as needed.
- Participants will be allowed to go home once they have had two negative tests for the virus. The tests will be given on two consecutive days....
Read the detailed description
The high morbidity and mortality associated with both pandemic and seasonal influenza, and the anticipation of future influenza pandemics, puts influenza front and center in infectious disease research. Because the natural history and pathogenesis of human influenza has not been well characterized and cannot be adequately studied in animal models or with current in vitro techniques, important questions about influenza pathogenesis can only be approached through human challenge studies.
Previous human challenge studies have addressed some aspects of the natural history of influenza by evaluating the timing of viral replication, shedding, clinical symptoms, and innate and adaptive immune responses. Although these studies have provided important information, in the United States, all but 1 were performed prior to 1990. Without exception, these studies had limitations due to the scope of the study and/or the scientific techniques available at that time.
The primary objective of this study is to determine the dose of influenza A 2009 H1N1 human challenge virus that will induce a mild to moderate uncomplicated influenza infection in healthy volunteers. This protocol will examine some of the basic questions that remain unanswered regarding the pathogenesis of influenza in humans, namely, a detailed clinical and immunological characterization of uncomplicated influenza viral pathogenesis in healthy adult volunteers.
Secondary objectives will evaluate clinical disease, length of viral shedding, and pathogenesis in those with influenza infection including identification of clinical markers of the disease. Notably, the exploratory objectives will seek to discover viral factors necessary for human infection/adaptation and to evaluate host immune response, viral replication, viral fitness, and the intrahost evolution.
Collaboration between National Institute of Allergy and Infectious Diseases (NIAID) investigators and outside scientists will generate opportunities to further develop and expand areas of clinical influenza research based on the proposed challenge model.
- Conditions
- Influenza
- Being tested
- Ca/04/2009/H1N1 Vero Grown Challenge Virus
- Keywords
- H1N1, Influenza, Human, Challenge Study, Healthy Volunteer
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ca/04/2009/H1N1 Vero Grown Challenge VirusBiological
The human challenge virus will be administered intranasally to each participant using a nasal sprayer. A total volume of up to 1 mL of virus will be administered.
| Study group | Role | What they receive |
|---|---|---|
| Challenge Virus | Experimental | The Ca/04/2009/H1N1 Vero Grown Challenge Virus was administered intranasally to each participant using a nasal sprayer. A total volume of up to 1 mL of virus will be administered. Receives: Biological: Ca/04/2009/H1N1 Vero Grown Challenge Virus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent MMID
Percent of individuals experiencing mild to moderate influenza infection (MMID, defined as active shedding and symptoms of influenza A) in each dosing group.
Measured: 67 days after influenza inoculation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2012 (estimated)
- Study startFeb 2012
- Primary completionDec 2013
- Study completionDec 2013
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.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for InfluenzaStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Matthew J Memoli, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01646138
- Sponsor's protocol ID
- 120077
- Other IDs
- 12-I-0077
- Status last verified
- Apr 2016
- First submitted
- 18 Jul 2012
- Last updated
- 9 May 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Data will be shared through the NIH data repository BTRIS - Biomedical Translational Research Information System
Publications
Hayden FG, Fritz R, Lobo MC, Alvord W, Strober W, Straus SE. Local and systemic cytokine responses during experimental human influenza A virus infection. Relation to symptom formation and host defense. J Clin Invest. 1998 Feb 1;101(3):643-9. doi: 10.1172/JCI1355.
PubMed 9449698Jameson J, Cruz J, Ennis FA. Human cytotoxic T-lymphocyte repertoire to influenza A viruses. J Virol. 1998 Nov;72(11):8682-9. doi: 10.1128/JVI.72.11.8682-8689.1998.
PubMed 9765409McAuley JL, Hornung F, Boyd KL, Smith AM, McKeon R, Bennink J, Yewdell JW, McCullers JA. Expression of the 1918 influenza A virus PB1-F2 enhances the pathogenesis of viral and secondary bacterial pneumonia. Cell Host Microbe. 2007 Oct 11;2(4):240-9. doi: 10.1016/j.chom.2007.09.001.
PubMed 18005742Memoli MJ, Han A, Walters KA, Czajkowski L, Reed S, Athota R, Angela Rosas L, Cervantes-Medina A, Park JK, Morens DM, Kash JC, Taubenberger JK. Influenza A Reinfection in Sequential Human Challenge: Implications for Protective Immunity and "Universal" Vaccine Development. Clin Infect Dis. 2020 Feb 14;70(5):748-753. doi: 10.1093/cid/ciz281.
PubMed 30953061Memoli MJ, Czajkowski L, Reed S, Athota R, Bristol T, Proudfoot K, Fargis S, Stein M, Dunfee RL, Shaw PA, Davey RT, Taubenberger JK. Validation of the wild-type influenza A human challenge model H1N1pdMIST: an A(H1N1)pdm09 dose-finding investigational new drug study. Clin Infect Dis. 2015 Mar 1;60(5):693-702. doi: 10.1093/cid/ciu924. Epub 2014 Nov 20.
PubMed 25416753
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Influenza A 2009 H1N1 Human Challenge Study in Healthy Adult Volunteers
- ClinicalTrials.gov ID
- NCT01646138
- Acronym / sponsor ID
- 120077
- Conditions
- Influenza
- Keywords
- H1N1, Influenza, Human, Challenge Study, Healthy Volunteer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Feb 2012
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 20 Jul 2012 (estimated)
- Results
- Posted 9 May 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- A challenge study exposes a person to a disease and allows researchers to study the disease through the body's healing process. An influenza challenge study that looks at different amounts of the flu virus can provide more information on the smallest amount needed to cause an infection. Researchers want to give one dose of the Influenza A H1N1 virus to healthy volunteers to see how the body responds to the virus.
Objectives:
- To find the smallest dose of Influenza A H1N1 virus that may cause a mild to moderate flu infection in a healthy adult.
- To study how the body s immune system responds to the virus.
Eligibility:
- Healthy volunteers at least 18 years of age.
- Participants must be willing to remain in isolation for a minimum of 9 days.
Design:
- Participants will be admitted to a hospital inpatient isolation unit. They will be screened with a physical exam and medical history. They will also have heart and lung function tests. Blood, urine, and nasal swab/wash samples will be collected.
- Participants will receive a single nasal spray of the flu virus. They will stay on the inpatient unit for at least 9 days.
- Participants will be monitored for the length of their stay. They will have frequent blood tests and other procedures as needed.
- Participants will be allowed to go home once they have had two negative tests for the virus. The tests will be given on two consecutive days....
Detailed description
The high morbidity and mortality associated with both pandemic and seasonal influenza, and the anticipation of future influenza pandemics, puts influenza front and center in infectious disease research. Because the natural history and pathogenesis of human influenza has not been well characterized and cannot be adequately studied in animal models or with current in vitro techniques, important questions about influenza pathogenesis can only be approached through human challenge studies.
Previous human challenge studies have addressed some aspects of the natural history of influenza by evaluating the timing of viral replication, shedding, clinical symptoms, and innate and adaptive immune responses. Although these studies have provided important information, in the United States, all but 1 were performed prior to 1990. Without exception, these studies had limitations due to the scope of the study and/or the scientific techniques available at that time.
The primary objective of this study is to determine the dose of influenza A 2009 H1N1 human challenge virus that will induce a mild to moderate uncomplicated influenza infection in healthy volunteers. This protocol will examine some of the basic questions that remain unanswered regarding the pathogenesis of influenza in humans, namely, a detailed clinical and immunological characterization of uncomplicated influenza viral pathogenesis in healthy adult volunteers.
Secondary objectives will evaluate clinical disease, length of viral shedding, and pathogenesis in those with influenza infection including identification of clinical markers of the disease. Notably, the exploratory objectives will seek to discover viral factors necessary for human infection/adaptation and to evaluate host immune response, viral replication, viral fitness, and the intrahost evolution.
Collaboration between National Institute of Allergy and Infectious Diseases (NIAID) investigators and outside scientists will generate opportunities to further develop and expand areas of clinical influenza research based on the proposed challenge model.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Challenge Virus | Experimental | Biological: Ca/04/2009/H1N1 Vero Grown Challenge VirusThe Ca/04/2009/H1N1 Vero Grown Challenge Virus was administered intranasally to each participant using a nasal sprayer. A total volume of up to 1 mL of virus will be administered. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (0 listed)
Key exclusion criteria (36 listed)
- Presence of self-reported or medically documented significant medical condition including but not limited to:
- Have close or household (i.e., share the same apartment or house) high-risk contacts including but not limited to:
- Individual with body mass index (BMI) less than or equal to 18.5 and greater than or equal to 40.
- Smokes more than 4 cigarettes or other tobacco products on weekly basis.
- Complete blood count (CBC) with differential outside of the NIH Department of Laboratory Medicine (DLM) normal reference range and deemed clinically significant by the PI.
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 |
|---|---|---|
| Ca/04/2009/H1N1 Vero Grown Challenge VirusThe human challenge virus will be administered intranasally to each participant using a nasal sprayer. A total volume of up to 1 mL of virus will be administered. | Biological | Challenge Virus |
Primary outcome
Percent MMID
Time frame: 67 days after influenza inoculation
Percent of individuals experiencing mild to moderate influenza infection (MMID, defined as active shedding and symptoms of influenza A) in each dosing group.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 9449698Hayden FG, Fritz R, Lobo MC, Alvord W, Strober W, Straus SE. Local and systemic cytokine responses during experimental human influenza A virus infection. Relation to symptom formation and host defense. J Clin Invest. 1998 Feb 1;101(3):643-9. doi: 10.1172/JCI1355.
- Background: PubMed 9765409Jameson J, Cruz J, Ennis FA. Human cytotoxic T-lymphocyte repertoire to influenza A viruses. J Virol. 1998 Nov;72(11):8682-9. doi: 10.1128/JVI.72.11.8682-8689.1998.
- Background: PubMed 18005742McAuley JL, Hornung F, Boyd KL, Smith AM, McKeon R, Bennink J, Yewdell JW, McCullers JA. Expression of the 1918 influenza A virus PB1-F2 enhances the pathogenesis of viral and secondary bacterial pneumonia. Cell Host Microbe. 2007 Oct 11;2(4):240-9. doi: 10.1016/j.chom.2007.09.001.
- Derived from this study: PubMed 30953061Memoli MJ, Han A, Walters KA, Czajkowski L, Reed S, Athota R, Angela Rosas L, Cervantes-Medina A, Park JK, Morens DM, Kash JC, Taubenberger JK. Influenza A Reinfection in Sequential Human Challenge: Implications for Protective Immunity and "Universal" Vaccine Development. Clin Infect Dis. 2020 Feb 14;70(5):748-753. doi: 10.1093/cid/ciz281.
- Derived from this study: PubMed 25416753Memoli MJ, Czajkowski L, Reed S, Athota R, Bristol T, Proudfoot K, Fargis S, Stein M, Dunfee RL, Shaw PA, Davey RT, Taubenberger JK. Validation of the wild-type influenza A human challenge model H1N1pdMIST: an A(H1N1)pdm09 dose-finding investigational new drug study. Clin Infect Dis. 2015 Mar 1;60(5):693-702. doi: 10.1093/cid/ciu924. Epub 2014 Nov 20.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Data will be shared through the NIH data repository BTRIS - Biomedical Translational Research Information System
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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.
Matthew J Memoli, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Ca/04/2009/H1N1 Vero Grown Challenge Virus in people with Influenza, run by National Institute of Allergy and Infectious Diseases (NIAID) 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 0 inclusion and 36 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 9 May 2016. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 9 May 2016). 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?
Percent MMID (time frame: 67 days after influenza inoculation). 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 NCT01646138, which also lists 5 linked publications.
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 9 May 2016.