Determine Minimally to Moderately Infective Dose (MMID) of Influenza A H3N2Phase 1NCT02594189
Influenza A H3N2 Human Challenge Study in Healthy Adult Volunteers
A Phase 1 study testing Live recombinantly derived A/Bethesda/MM1/H3N2 virus in people with Determine Minimally to Moderately Infective Dose (MMID) of Influenza A H3N2, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
Background: Influenza A H3N2 is a flu virus. Symptoms include fever, cough, and runny nose. It can also be more serious. Researchers want to know more about how influenza causes disease in people. They hope to develop new vaccines and treatments for flu infection. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Determine Minimally to Moderately Infective Dose (MMID) of Influenza A H3N2
- What is being tested?
- Live recombinantly derived A/Bethesda/MM1/H3N2 virus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Oct 2015to 1 Nov 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- No healthy volunteers
- 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., insulin-dependent diabetes mellitus, renal dysfunction, hemoglobinopathies).
- Immunosuppression or ongoing malignancy.
- Neurological and neurodevelopmental conditions (e.g., cerebral palsy, epilepsy, stroke, seizures).
Show all 37Show fewer
- Post infectious or post vaccine neurological sequelae.
- Have close or household (i.e., share the same apartment or house) high-risk contacts including but not limited to:
- Persons more than or equal to 65 years of age.
- Children less than or equal to 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 medical conditions (e.g., insulindependent diabetes mellitus, renal dysfunction, hemoglobinopathies).
- Immunosuppression or cancer.
- Neurological and neurodevelopmental conditions (e.g., cerebral palsy, epilepsy, stroke, seizures).
- Persons who are receiving long-term aspirin therapy.
- Women who are pregnant, trying to become pregnant, or breastfeeding.
- Individual with body mass index (BMI) less than or equal to 18.5 and more than 40.
- Smokes more than 4 cigarettes or other tobacco products on weekly basis.
- Complete blood count (CBC) with differential outside of the NIH 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 as deemed by the PI on electrocardiogram (EKG)
- Clinically significant abnormality as deemed by the PI on echocardiographic testing (ECHO).
- Clinically significant abnormality as deemed by the PI on the Pulmonary Function Test (PFT).
- 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 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 PI, 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
Background:
Influenza A H3N2 is a flu virus. Symptoms include fever, cough, and runny nose. It can also be more serious. Researchers want to know more about how influenza causes disease in people. They hope to develop new vaccines and treatments for flu infection.
Read more
Objective:
To find the smallest amount of Influenza A H3N2 virus that causes a mild to moderate flu infection in healthy people. Also, to study the body s immune response to this virus and how the infection develops.
Eligibility:
Healthy people ages 18 50 who are:
Non-smokers or non-habitual smokers
Willing to not smoke for at least 9 days
Design:
Participants will be screened under NIAID protocol #11-I-0183
Participants will stay at an isolation unit at the clinic for at least 9 days. They will remain in the isolation unit except for study-specific activities.
The influenza virus will be sprayed into the nose.
Participants will be monitored 24 hours a day. They will have tests, including:
Medical history
Physical exam
Daily questionnaires about symptoms
Blood and urine tests
Nasal wash and swab: A small tube of salt water is placed in the nose to wash it. It then collects the
fluid. Or the inside of the nose is rubbed with a swab.
ECG: Measures the heart s electrical signals
ECHO: Sound waves take pictures of the heart
PFTs/Spirometry: They will blow into a machine that measures the air they blow.
Participants will be discharged after they test negative for influenza A.
Participants will return to the clinic for 4 follow-up visits over 8 weeks. They may complete questionnaires at home.
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.
Although studies of influenza in healthy volunteers have played an important role in addressing aspects of the natural history of influenza disease and developing novel antivirals, prior to recently these important studies had not been performed in the US in over a decade. The H1N1 challenge studies we have performed since 2012 have sought to improve upon the studies done in the past and address many of the limitations due to the scope of the studies and/or the scientific techniques available at that time. We have successfully developed an H1N1 model that had been used to address important questions regarding correlates of protection and is now being implemented to develop new drugs and vaccines. We hope to develop H3N2 models that can be just as useful.
The primary objective of this study is to determine the dose of influenza A H3N2 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 H3N2 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 NIAID investigators and outside scientists will generate opportunities to further develop and expand areas of clinical influenza research based on the proposed H3N2 challenge model.
- Being tested
- Live recombinantly derived A/Bethesda/MM1/H3N2 virus
- Keywords
- Influenza A, H3N2, Challenge Model, Influenza, Human Challenge
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Live recombinantly derived A/Bethesda/MM1/H3N2 virusOther
The human challenge virus will be administered intranasally to each participant using a nasal sprayer. A total volume of up to 2mL of virus will be administered.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Other | The human challenge virus will be administered intranasally to each participant using a nasal sprayer. A total volume of up to 2mL of virus will be administered. Receives: Other: Live recombinantly derived A/Bethesda/MM1/H3N2 virus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the minimally to moderately infective dose (MMID) of influenza A H3N2 human challenge virus, defined as the dose that induces uncomplicated mild to moderate influenza infection in at least 60% of healthy volunteers.
Measured: 2 yr
Secondary outcomes (1)
Evaluate clinical disease, identify clinical markers, and observe initiation of shedding, length of shedding, and pathogenesis in participants with influenza infection.
Measured: 1yr
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2015 (estimated)
- Study start31 Oct 2015
- Primary completion1 Nov 2017
- Study completion1 Nov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Determine Minimally to Moderately Infective Dose (MMID) of Influenza A H3N2Studies 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
- 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
- NCT02594189
- Sponsor's protocol ID
- 160008
- Other IDs
- 16-I-0008
- Status last verified
- 1 Nov 2017
- First submitted
- 31 Oct 2015
- Last updated
- 3 Dec 2019
- Results posted
- No
Publications
Carrat F, Vergu E, Ferguson NM, Lemaitre M, Cauchemez S, Leach S, Valleron AJ. Time lines of infection and disease in human influenza: a review of volunteer challenge studies. Am J Epidemiol. 2008 Apr 1;167(7):775-85. doi: 10.1093/aje/kwm375. Epub 2008 Jan 29.
PubMed 18230677Anderson MJ, Heath RB. Cell mediated immunity in experimental influenza and parainfluenza infection. Dev Biol Stand. 1977 Jun 1-3;39:379-83.
PubMed 203505Brown TA, Murphy BR, Radl J, Haaijman JJ, Mestecky J. Subclass distribution and molecular form of immunoglobulin A hemagglutinin antibodies in sera and nasal secretions after experimental secondary infection with influenza A virus in humans. J Clin Microbiol. 1985 Aug;22(2):259-64. doi: 10.1128/jcm.22.2.259-264.1985.
PubMed 4031039Han A, Czajkowski LM, Donaldson A, Baus HA, Reed SM, Athota RS, Bristol T, Rosas LA, Cervantes-Medina A, Taubenberger JK, Memoli MJ. A Dose-finding Study of a Wild-type Influenza A(H3N2) Virus in a Healthy Volunteer Human Challenge Model. Clin Infect Dis. 2019 Nov 27;69(12):2082-2090. doi: 10.1093/cid/ciz141.
PubMed 30770534
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Influenza A H3N2 Human Challenge Study in Healthy Adult Volunteers
- ClinicalTrials.gov ID
- NCT02594189
- Acronym / sponsor ID
- 160008
- Keywords
- Influenza A, H3N2, Challenge Model, Influenza, Human Challenge
- Phase
- Phase 1
- 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
- 31 Oct 2015
- Primary completion
- 1 Nov 2017 (actual)
- Study completion
- 1 Nov 2017 (actual)
- First posted
- 3 Nov 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
Influenza A H3N2 is a flu virus. Symptoms include fever, cough, and runny nose. It can also be more serious. Researchers want to know more about how influenza causes disease in people. They hope to develop new vaccines and treatments for flu infection.
Objective:
To find the smallest amount of Influenza A H3N2 virus that causes a mild to moderate flu infection in healthy people. Also, to study the body s immune response to this virus and how the infection develops.
Eligibility:
Healthy people ages 18 50 who are:
Non-smokers or non-habitual smokers
Willing to not smoke for at least 9 days
Design:
Participants will be screened under NIAID protocol #11-I-0183
Participants will stay at an isolation unit at the clinic for at least 9 days. They will remain in the isolation unit except for study-specific activities.
The influenza virus will be sprayed into the nose.
Participants will be monitored 24 hours a day. They will have tests, including:
Medical history
Physical exam
Daily questionnaires about symptoms
Blood and urine tests
Nasal wash and swab: A small tube of salt water is placed in the nose to wash it. It then collects the
fluid. Or the inside of the nose is rubbed with a swab.
ECG: Measures the heart s electrical signals
ECHO: Sound waves take pictures of the heart
PFTs/Spirometry: They will blow into a machine that measures the air they blow.
Participants will be discharged after they test negative for influenza A.
Participants will return to the clinic for 4 follow-up visits over 8 weeks. They may complete questionnaires at home.
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.
Although studies of influenza in healthy volunteers have played an important role in addressing aspects of the natural history of influenza disease and developing novel antivirals, prior to recently these important studies had not been performed in the US in over a decade. The H1N1 challenge studies we have performed since 2012 have sought to improve upon the studies done in the past and address many of the limitations due to the scope of the studies and/or the scientific techniques available at that time. We have successfully developed an H1N1 model that had been used to address important questions regarding correlates of protection and is now being implemented to develop new drugs and vaccines. We hope to develop H3N2 models that can be just as useful.
The primary objective of this study is to determine the dose of influenza A H3N2 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 H3N2 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 NIAID investigators and outside scientists will generate opportunities to further develop and expand areas of clinical influenza research based on the proposed H3N2 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 |
|---|---|---|
| 1 | Other | Other: Live recombinantly derived A/Bethesda/MM1/H3N2 virusThe human challenge virus will be administered intranasally to each participant using a nasal sprayer. A total volume of up to 2mL of virus will be administered. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (0 listed)
Key exclusion criteria (37 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 more than 40.
- Smokes more than 4 cigarettes or other tobacco products on weekly basis.
- Complete blood count (CBC) with differential outside of the NIH 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 |
|---|---|---|
| Live recombinantly derived A/Bethesda/MM1/H3N2 virusThe human challenge virus will be administered intranasally to each participant using a nasal sprayer. A total volume of up to 2mL of virus will be administered. | Other | 1 |
Primary outcome
Determine the minimally to moderately infective dose (MMID) of influenza A H3N2 human challenge virus, defined as the dose that induces uncomplicated mild to moderate influenza infection in at least 60% of healthy volunteers.
Time frame: 2 yr
1 secondary outcome
Evaluate clinical disease, identify clinical markers, and observe initiation of shedding, length of shedding, and pathogenesis in participants with influenza infection.
Time frame: 1yr
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2019.
- Background: PubMed 18230677Carrat F, Vergu E, Ferguson NM, Lemaitre M, Cauchemez S, Leach S, Valleron AJ. Time lines of infection and disease in human influenza: a review of volunteer challenge studies. Am J Epidemiol. 2008 Apr 1;167(7):775-85. doi: 10.1093/aje/kwm375. Epub 2008 Jan 29.
- Background: PubMed 203505Anderson MJ, Heath RB. Cell mediated immunity in experimental influenza and parainfluenza infection. Dev Biol Stand. 1977 Jun 1-3;39:379-83.
- Background: PubMed 4031039Brown TA, Murphy BR, Radl J, Haaijman JJ, Mestecky J. Subclass distribution and molecular form of immunoglobulin A hemagglutinin antibodies in sera and nasal secretions after experimental secondary infection with influenza A virus in humans. J Clin Microbiol. 1985 Aug;22(2):259-64. doi: 10.1128/jcm.22.2.259-264.1985.
- Derived from this study: PubMed 30770534Han A, Czajkowski LM, Donaldson A, Baus HA, Reed SM, Athota RS, Bristol T, Rosas LA, Cervantes-Medina A, Taubenberger JK, Memoli MJ. A Dose-finding Study of a Wild-type Influenza A(H3N2) Virus in a Healthy Volunteer Human Challenge Model. Clin Infect Dis. 2019 Nov 27;69(12):2082-2090. doi: 10.1093/cid/ciz141.
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 study testing Live recombinantly derived A/Bethesda/MM1/H3N2 virus in people with Determine Minimally to Moderately Infective Dose (MMID) of Influenza A H3N2, 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 37 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 Dec 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. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Determine the minimally to moderately infective dose (MMID) of influenza A H3N2 human challenge virus, defined as the dose that induces uncomplicated mild to moderate influenza infection in at least 60% of healthy volunteers. (time frame: 2 yr). 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 NCT02594189, which also lists 4 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 3 Dec 2019.