Influenza, HumanPhase 1NCT02950688
Safety and Effectiveness of a Seasonal Live Attenuated Influenza Vaccine in a Human Challenge Model of Infection With Wild-type (wt) Influenza A/California/2009 (H1N1)-Like Virus
A Phase 1 study testing Seasonal LAIV and Wild-type A/California/2009-like Influenza Virus in people with Influenza, Human, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
The purpose of this study is to evaluate the immune response produced by a seasonal live attenuated influenza vaccine (LAIV) when compared to placebo. The initial vaccination will be followed 2 months later by an inpatient trial evaluating safety, infectivity, clinical response, and viral shedding after exposure to… Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Influenza, Human
- What is being tested?
- Seasonal LAIV and Wild-type A/California/2009-like Influenza Virus
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Start not givento Dec 2020
- 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 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Adult males and non-pregnant females between 18 years and 45 years of age. Children will not be recruited or enrolled in this study for safety considerations and because of the need for isolation.
- General good health, without significant medical illness, physical examination findings, or significant laboratory abnormalities as determined by the investigator.
- Likely to be susceptible to the challenge virus as determined by a baseline serum HAI antibody titer to the A/California/09 wild-type virus of 1:8 or less.
- Agree to storage of blood specimens for future research.
- Available for the duration of the trial.
- Willingness to participate in the study as evidenced by signing the informed consent document.
- Female subjects must agree to use effective birth control methods for the duration of the study (for example, pharmacologic contraceptives including oral, parenteral, and transcutaneous delivery; condoms with spermicide; diaphragm with spermicide; intrauterine device; abstinence from heterosexual intercourse, surgical sterilization). All female subjects will be considered being of child-bearing potential except those who have undergone hysterectomy and those in whom menopause occurred at least 1 year prior to the study.
Who cannot join
- Pregnancy as determined by a positive human choriogonadotropin (beta-HCG) test.
- Currently breast-feeding.
- Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, endocrinologic or renal disease by history, physical examination, and/or laboratory studies including urine testing. Levels of alanine aminotransferase (ALT), aspartate transaminase (AST), bilirubin greater than 2 times the upper limit of normal (ULN) or otherwise clinically significant as determined by the Principal Investigator (PI), will be exclusionary at baseline, prior to vaccination. Complete blood count (CBC) with differential outside of the normal reference range and deemed clinically significant by the PI.
- Body Mass Index (BMI) of less than 18.5 or greater than 40.
- Behavioral or cognitive impairment or psychiatric disease that in the opinion of the investigator affects the ability of the subject to understand and cooperate with the study protocol.
- Have medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months.
Show all 28Show fewer
- Other condition that in the opinion of the investigator would jeopardize the safety or rights of a subject participating in the trial or would render the subject unable to comply with the protocol.
- History of anaphylaxis.
- Allergy to oseltamivir as determined by subject report.
- Current diagnosis of asthma or reactive airway disease (within the past 2 years).
- History of Guillain-Barré Syndrome.
- Known immunodeficiency syndrome.
- Use of corticosteroids (excluding topical preparations) or immunosuppressive drugs within 30 days prior to vaccination.
- Receipt of a live vaccine within 4 weeks or a killed vaccine within 2 weeks prior to study vaccination.
- Receipt of any unlicensed drug within 3 months or 5.5 half-lives (whichever is greater) or any unlicensed vaccine within 6 months of enrollment.
- History of a surgical splenectomy.
- Receipt of blood or blood-derived products (including immunoglobulin) within 6 months prior to study vaccination.
- Current smoker unwilling to stop smoking for the In-patient Challenge Phase of the study.
- A current smoker includes anyone stating they currently smoke any amount of a tobacco product.
- The decision to exclude a potential subject is determined by medical history and a clinician's clinical judgment based on the physical examination.
- After admission to the unit, nicotine patches will be provided to current smokers who request them for the inpatient portion of the study.
- Allergy to eggs or egg products.
- Household contacts of individuals at higher risk for influenza-related complications, including: Persons greater than or equal to 65 years of age or less than 5 years of age; or persons with chronic pulmonary disease (e.g., asthma, emphysema), chronic cardiovascular disease (e.g., cardiomyopathy, congestive heart failure, ischemic heart disease), metabolic disease (e.g., diabetes mellitus, renal dysfunction, hemoglobinopathies), immunosuppression, neurological and neurodevelopmental conditions, children and teenagers who are receiving long-term aspirin therapy, or women who are pregnant or who are trying to become pregnant.
- Positive urine drug toxicology test indicating narcotic use/dependency.
- Positive ELISA and confirmatory tests for human immunodeficiency virus-1 (HIV-1), hepatitis C virus (HCV), or hepatitis B (Positive hepatitis B virus surface antigen).
- Clinically significant abnormalities on ECG.
- Clinically significant abnormality as deemed by the PI on echocardiographic testing.
- Known close contact with anyone known to have influenza or influenza-like illness in the past 7 days.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Rochester Medical Center
Rochester, New York, 14642
About this study
Official title: Evaluation of Correlates of Protective Efficacy of Seasonal Live Attenuated Influenza Vaccine (LAIV) by Utilization of a Human Challenge Model of Infection With Wild-type (wt) Influenza A/California/2009 (H1N1)-Like Virus
The purpose of this study is to evaluate the immune response produced by a seasonal live attenuated influenza vaccine (LAIV) when compared to placebo. The initial vaccination will be followed 2 months later by an inpatient trial evaluating safety, infectivity, clinical response, and viral shedding after exposure to the wild-type A/California/2009-like influenza challenge virus.
Read the detailed description
This study will evaluate the immune response produced by a seasonal LAIV. The initial vaccination will be followed 2 months later by an open-label inpatient trial evaluating the subsequent response (safety, infectivity, clinical response, and viral shedding) following administration of the wild-type A/California/2009-like influenza challenge virus.
Healthy adult participants will be randomized into two groups. On Day 0, Group 1 will receive a single dose of an intranasal LAIV. Group 2 will receive a single dose of intranasal placebo. Study visits will occur on Days 0, 3, 7, 14, and 28.
On Day 54, participants will be admitted to the isolation unit for the inpatient portion of the study, and both groups will receive an intranasal dose of wild-type A/California/2009-like influenza challenge virus on Day 56. On Day 65, participants who are no longer shedding virus will be discharged.
Follow-up study visits will occur after discharge from the isolation unit on Days 70, 84, 112, and 180. Study visits during either the inpatient or outpatient portions of the trial may include physical examinations, collection of blood and urine samples, electrocardiogram (ECG), nasal washes and swabs, and nasal mucus weighing.
- Conditions
- Influenza, Human
- Being tested
- Seasonal LAIV, Placebo, Wild-type A/California/2009-like Influenza Virus
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Seasonal LAIVBiological
Also called FluMist Quadrivalent®
10^7.0 fluorescent focus units (FFU); administered by intranasal spray
PlaceboBiological
Administered by intranasal spray
Wild-type A/California/2009-like Influenza VirusBiological
Approximately 3.5 x 10^6 TCID50; administered intranasally
| Study group | Role | What they receive |
|---|---|---|
| Group 1: Seasonal LAIV | Experimental | Participants will receive 1 dose of seasonal LAIV on Day 0. They will receive 1 dose of the wild-type A/California/2009-like influenza challenge virus on Day 56. Receives: Biological: Seasonal LAIV; Biological: Wild-type A/California/2009-like Influenza Virus |
| Group 2: Placebo | Placebo comparator | Participants will receive 1 dose of placebo on Day 0. They will receive 1 dose of the wild-type A/California/2009-like influenza challenge virus on Day 56. Receives: Biological: Placebo; Biological: Wild-type A/California/2009-like Influenza Virus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of any reactogenicity events after administration of seasonal LAIV
Measured: Measured through Day 180
Frequency of significant increases in nasal secretion hemagglutination (HA)-specific antibody assessed by enzyme-linked immunosorbent assay (ELISA)
Measured: Measured through Day 84
Frequency of instances of greater than 200 influenza-specific interferon-gamma-secreting cells per million lymphocytes as assessed by enzyme-linked immuno spot assay (ELISPOT)
Measured: Measured on Day 28 after immunization
Frequency of detection of influenza-specific immunoglobulin G (IgG) or immunoglobulin A (IgA) secreting B cells assessed by antibody secreting cells (ASC) assay
Measured: Measured on Day 7 following vaccination
Frequency of challenge virus shedding on one or more days on Days 56-63 as assessed by culture or real-time reverse transcriptase polymerase chain reaction (rRT-PCR)
Measured: Measured through Day 63
A 4-fold or greater increase in either hemagglutination-inhibition (HAI) or microneutralization (MN) antibody when compared to pre-challenge samples, as assessed by HAI assays
Measured: Measured through Day 56
A 4-fold or greater increase in either hemagglutination-inhibition (HAI) or microneutralization (MN) antibody when compared to pre-challenge samples, as assessed by MN assays
Measured: Measured through Day 56
A 4-fold or greater increase in either hemagglutination-inhibition (HAI) or microneutralization (MN) antibody when compared to pre-challenge samples, as assessed by blood serum titer
Measured: Measured through Day 56
Clinical symptoms recording of 10 key influenza symptoms (cough, sore throat, stuffy nose, dyspnea, fatigue, headache, myalgias, nausea, diarrhea, and feverishness) on an analog scale of severity
Measured: Measured through Day 180
Area under the curve (AUC) of symptom severity
Measured: Measured through Day 180
Total nasal mucus weight
Nasal mucus weights will be determined by collecting tissues over 24 hours, weighing them and subtracting the dry weight.
Measured: Measured through Day 180
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2016 (estimated)
- Primary completionDec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Influenza, HumanStudies 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- John Treanor, M.D., Principal investigator, University of Rochester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02950688
- Sponsor's protocol ID
- URMC 15-001
- Status last verified
- Nov 2017
- First submitted
- 26 Oct 2016
- Last updated
- 29 Nov 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Correlates of Protective Efficacy of Seasonal Live Attenuated Influenza Vaccine (LAIV) by Utilization of a Human Challenge Model of Infection With Wild-type (wt) Influenza A/California/2009 (H1N1)-Like Virus
- ClinicalTrials.gov ID
- NCT02950688
- Acronym / sponsor ID
- URMC 15-001
- Conditions
- Influenza, Human
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Primary completion
- Dec 2020 (estimated)
- First posted
- 1 Nov 2016 (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.
The purpose of this study is to evaluate the immune response produced by a seasonal live attenuated influenza vaccine (LAIV) when compared to placebo. The initial vaccination will be followed 2 months later by an inpatient trial evaluating safety, infectivity, clinical response, and viral shedding after exposure to the wild-type A/California/2009-like influenza challenge virus.
Detailed description
This study will evaluate the immune response produced by a seasonal LAIV. The initial vaccination will be followed 2 months later by an open-label inpatient trial evaluating the subsequent response (safety, infectivity, clinical response, and viral shedding) following administration of the wild-type A/California/2009-like influenza challenge virus.
Healthy adult participants will be randomized into two groups. On Day 0, Group 1 will receive a single dose of an intranasal LAIV. Group 2 will receive a single dose of intranasal placebo. Study visits will occur on Days 0, 3, 7, 14, and 28.
On Day 54, participants will be admitted to the isolation unit for the inpatient portion of the study, and both groups will receive an intranasal dose of wild-type A/California/2009-like influenza challenge virus on Day 56. On Day 65, participants who are no longer shedding virus will be discharged.
Follow-up study visits will occur after discharge from the isolation unit on Days 70, 84, 112, and 180. Study visits during either the inpatient or outpatient portions of the trial may include physical examinations, collection of blood and urine samples, electrocardiogram (ECG), nasal washes and swabs, and nasal mucus weighing.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1: Seasonal LAIV | Experimental | Biological: Seasonal LAIV, Biological: Wild-type A/California/2009-like Influenza VirusParticipants will receive 1 dose of seasonal LAIV on Day 0. They will receive 1 dose of the wild-type A/California/2009-like influenza challenge virus on Day 56. |
| Group 2: Placebo | Placebo comparator | Biological: Placebo, Biological: Wild-type A/California/2009-like Influenza VirusParticipants will receive 1 dose of placebo on Day 0. They will receive 1 dose of the wild-type A/California/2009-like influenza challenge virus on Day 56. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Adult males and non-pregnant females between 18 years and 45 years of age. Children will not be recruited or enrolled in this study for safety considerations and because of the need for isolation.
- General good health, without significant medical illness, physical examination findings, or significant laboratory abnormalities as determined by the investigator.
- Likely to be susceptible to the challenge virus as determined by a baseline serum HAI antibody titer to the A/California/09 wild-type virus of 1:8 or less.
- Agree to storage of blood specimens for future research.
- Available for the duration of the trial.
Key exclusion criteria (28 listed)
- Pregnancy as determined by a positive human choriogonadotropin (beta-HCG) test.
- Currently breast-feeding.
- Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, endocrinologic or renal disease by history, physical examination, and/or laboratory studies including urine testing. Levels of alanine aminotransferase (ALT), aspartate transaminase (AST), bilirubin greater than 2 times the upper limit of normal (ULN) or otherwise clinically significant as determined by the Principal Investigator (PI), will be exclusionary at baseline, prior to vaccination. Complete blood count (CBC) with differential outside of the normal reference range and deemed clinically significant by the PI.
- Body Mass Index (BMI) of less than 18.5 or greater than 40.
- Behavioral or cognitive impairment or psychiatric disease that in the opinion of the investigator affects the ability of the subject to understand and cooperate with the study protocol.
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 |
|---|---|---|
| Seasonal LAIVAlso: FluMist Quadrivalent®10^7.0 fluorescent focus units (FFU); administered by intranasal spray | Biological | Group 1: Seasonal LAIV |
| PlaceboAdministered by intranasal spray | Biological | Group 2: Placebo |
| Wild-type A/California/2009-like Influenza VirusApproximately 3.5 x 10^6 TCID50; administered intranasally | Biological | Group 1: Seasonal LAIV, Group 2: Placebo |
Primary outcome
Frequency of any reactogenicity events after administration of seasonal LAIV
Time frame: Measured through Day 180
Frequency of significant increases in nasal secretion hemagglutination (HA)-specific antibody assessed by enzyme-linked immunosorbent assay (ELISA)
Time frame: Measured through Day 84
Frequency of instances of greater than 200 influenza-specific interferon-gamma-secreting cells per million lymphocytes as assessed by enzyme-linked immuno spot assay (ELISPOT)
Time frame: Measured on Day 28 after immunization
Frequency of detection of influenza-specific immunoglobulin G (IgG) or immunoglobulin A (IgA) secreting B cells assessed by antibody secreting cells (ASC) assay
Time frame: Measured on Day 7 following vaccination
Frequency of challenge virus shedding on one or more days on Days 56-63 as assessed by culture or real-time reverse transcriptase polymerase chain reaction (rRT-PCR)
Time frame: Measured through Day 63
A 4-fold or greater increase in either hemagglutination-inhibition (HAI) or microneutralization (MN) antibody when compared to pre-challenge samples, as assessed by HAI assays
Time frame: Measured through Day 56
A 4-fold or greater increase in either hemagglutination-inhibition (HAI) or microneutralization (MN) antibody when compared to pre-challenge samples, as assessed by MN assays
Time frame: Measured through Day 56
A 4-fold or greater increase in either hemagglutination-inhibition (HAI) or microneutralization (MN) antibody when compared to pre-challenge samples, as assessed by blood serum titer
Time frame: Measured through Day 56
Clinical symptoms recording of 10 key influenza symptoms (cough, sore throat, stuffy nose, dyspnea, fatigue, headache, myalgias, nausea, diarrhea, and feverishness) on an analog scale of severity
Time frame: Measured through Day 180
Area under the curve (AUC) of symptom severity
Time frame: Measured through Day 180
Total nasal mucus weight
Time frame: Measured through Day 180
Nasal mucus weights will be determined by collecting tissues over 24 hours, weighing them and subtracting the dry weight.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2017.
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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.
John Treanor, M.D. principal investigator
University of Rochester
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 Seasonal LAIV and Wild-type A/California/2009-like Influenza Virus in people with Influenza, Human, 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 7 inclusion and 28 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: withdrawn, as of the sponsor's last update on 29 Nov 2017. 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Frequency of any reactogenicity events after administration of seasonal LAIV (time frame: Measured through Day 180). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 29 Nov 2017.