InfluenzaPhase 1NCT00231907
A Phase I Safety and Immunogenicity Study of Mix and Match of Licensed Flu Vaccine and Flumist
A Phase 1 study testing FluMist and Fluzone in people with Influenza, run by National Institute of Allergy and Infectious Diseases (NIAID) at 3 sites in United States.
Trial summary
The purpose of this research is to compare the safety and ability to stimulate antibodies (part of the bodies proteins that fight infections) of two influenza (flu) vaccines given to children 12 to 35 months old. Read more about this study
- Who is it for?
- Ages 12 to 35 monthsHealthy volunteers can take part
- Conditions the study is for
- Influenza
- What is being tested?
- FluMist and Fluzone
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 3 sitesUnited States
- Study dates
- Sep 2005to Mar 2007
- 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 12 to 35 months
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Twelve to 35 months of age at enrollment.
- Minimum weight of 8 kg.
- In good health, as determined by parent/guardian verbal medical history and physical examination by clinical investigator.
- Parent/guardian available by telephone for safety data collection through 6 months post-dose 2.
- Ability of parent/guardian to understand and comply with the requirements of the protocol.
- Signed informed consent document and Health Insurance Portability and Accountability Act (HIPAA) authorization by the parent/guardian prior to performance of any study procedures.
Who cannot join
- History of hypersensitivity to any component of LAIV or TIV, including egg or egg products.
- History of hypersensitivity to gentamicin.
- Known or suspected immune deficiency diseases or immunosuppressed or have altered or compromised immune status as a consequence of treatment with immunosuppressive therapies.
- Known close contact with a severely immunocompromised person, such as someone currently in isolation secondary to a bone marrow transplantation (LAIV recipients should avoid close contact with severely immunocompromised individuals for at least 7 days after vaccination).
- History of chronic underlying medical conditions such as chronic disorders of the cardiovascular and pulmonary systems, chronic metabolic diseases (including diabetes), renal dysfunction, or hemoglobinopathies.
- History of Guillain-Barré syndrome.
Show all 16Show fewer
- History of asthma or reactive airways disease.
- Acute febrile (>99.6 degrees Fahrenheit axillary) and/or respiratory illness, within the 72 hours prior to enrollment.
- Use of aspirin or aspirin containing products in the month prior to enrollment or anticipated use during the study.
- Administration of any intranasal medication within 2 weeks prior to enrollment or expected receipt during this study.
- Previous receipt of an influenza vaccine.
- Administration of any live virus vaccine within 4 weeks prior to enrollment or (other than study vaccine) planned receipt of another live virus vaccine before completion of the 2 weeks after the last vaccination in this study*
- Administration of any inactivated vaccine within 2 weeks prior to enrollment or planned receipt of another inactivated vaccine before 2 weeks after the last vaccination in this study*
- Participation in another investigational trial or administration of any investigational drug within 1 month prior to enrollment or during this study.
- Any condition that in the opinion of the investigator would interfere with the interpretation or evaluation of the vaccine.
- Routine immunizations can be resumed after the memory aid period following dose 2.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Vanderbilt University
Nashville, Tennessee, 37232
Saint Louis University
St Louis, Missouri, 63104
About this study
Official title: Influenza Vaccines: Mix and Match of Trivalent Inactivated Influenza (TIV) and Live Attenuated Influenza Vaccine (LAIV), a Phase I Safety, Immunogenicity, and Viral Shedding Study
The purpose of this research is to compare the safety and ability to stimulate antibodies (part of the bodies proteins that fight infections) of two influenza (flu) vaccines given to children 12 to 35 months old. The two flu vaccines being compared are: trivalent inactivated influenza virus vaccine (TIV), a killed virus vaccine given as a shot licensed for use in children 6 months of age or older and live attenuated influenza vaccine (LAIV), a live (but weakened) virus vaccine licensed for children 5 years old and older given as a nose spray. The strains of the viruses have been weakened so that they do not cause typical influenza illness, but may allow the body to develop protection against the flu. LAIV vaccine is not licensed for children less than five years of age, therefore its use in this study is investigational. Participation is approximately 7 months in duration.
Read the detailed description
This multi-site study is a phase I, open-label, 4-arm trial to evaluate 2 doses of influenza vaccine separated by 30 days. The vaccine will either be two doses of a single vaccine or a combination of vaccine products. FluMist®, a cold-adapted live attenuated influenza vaccine (LAIV), will be administered intranasally via spray applicator. Administration of FluMist in children less than 5 years of age is investigational. FluZone®, a trivalent inactivated influenza vaccine (TIV) licensed for use in children 6 months of age or older, will be administered intramuscularly (IM) to the anterolateral thigh muscle or deltoid muscle. Healthy children, ages 12 to 35 months old, who are representative of the population base of the vaccinating recruitment area, will be enrolled in this study at 3 sites. The primary study objective is to compare the safety and immunogenicity of two doses of licensed TIV or two doses of licensed LAIV with the safety and immunogenicity of a single dose of LAIV that is boosted with a dose of TIV versus children who receive an initial dose of TIV followed by a booster dose of LAIV among children 12 to 35 months of age. The secondary objective is to develop preliminary safety data on these combined vaccine regimes, and to evaluate the possibility that a single dose of TIV will either reduce the potential common side effects of LAIV or reduce the viral shedding associated with LAIV in children and to evaluate LAIV as a "primary" dose vaccine and TIV as a "booster vaccine" for inducing serum Hemagglutination Inhibition (HAI) antibodies. Vaccinees will be followed post-vaccination for safety, reactogenicity and immunogenicity. Patterns of viral shedding will be assessed 4 days after vaccination with LAIV. A final 6-month post-dose two vaccination contact will be made for serious adverse event data collection. Specifically, the investigators will assess the ability of LAIV to prime for a secondary immune response when TIV is given as a booster vaccine, and the investigators will evaluate TIV as a priming event for LAIV booster vaccine. Control groups will include TIV/TIV and LAIV/LAIV groups. The primary outcome measures for the study will be: assessment of post-dose 2 hemagglutination inhibition (HAI) antibodies to each of the 3 strains of influenza contained in the vaccine, safety assessment of each of the vaccines in combination vaccine. The secondary outcome measures include post-dose 1 HAI antibody titers and viral shedding after intranasal vaccination with live attenuated influenza vaccine. An additional secondary outcome will be assessment of secretory Immunoglobulin (Ig) A in nasal wash samples manifested after 1 or 2 doses of vaccine. An additional outcome will be Cell Mediated Immunity after 1 or 2 doses of vaccine. Blood will be collected on days 0, 30 and 60 for antibody detection. Nasal washes will be collected on day 0, 30 and 60 for secretory antibody measurements. A throat and nose swab sample will be collected on day 3 to 5 post LAIV vaccination to assess viral shedding and as dictated by presence of illness symptoms for viral culturing for two weeks after each dose of either LAIV or TIV vaccine. Up to 20 eligible participants will be enrolled in each of the 4 vaccination groups. As a four-arm trial with only active vaccine being administered by two different dosing routes, there will be no blinding to study assignment. Study duration is up to 3 years and individual participant duration is approximately 7 months.
- Conditions
- Influenza
- Being tested
- FluMist, Fluzone
- Keywords
- influenza, vaccine, TIV, LAIV, booster, children
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FluMistBiological
Live attenuated influenza vaccine (LAIV) containing approximately 10^7 TCID50 of each of the 3 influenza strains. 0.5 mL total dose volume administered intranasally via spray applicator (approximately 0.25 mL into each nostril). Administration of Flumist in children under 5 years of age is investigational.
FluzoneBiological
Trivalent inactivated vaccine (TIV), licensed Fluzone preservative free pediatric dose, 0.25 mL administered intramuscularly to the anterolateral thigh muscle or deltoid muscle.
| Study group | Role | What they receive |
|---|---|---|
| Vaccine 1: TIV. Vaccine 2: TIV. | Active comparator | Vaccine 1: TIV. Vaccine 2: TIV. Receives: Biological: Fluzone |
| Vaccine 1: LAIV. Vaccine 2: TIV. | Experimental | Vaccine 1: LAIV. Vaccine 2: TIV. Receives: Biological: FluMist; Biological: Fluzone |
| Vaccine 1: LAIV. Vaccine 2: LAIV. | Experimental | Vaccine 1: LAIV. Vaccine 2: LAIV. Receives: Biological: FluMist |
| Vaccine 1: TIV. Vaccine 2: LAIV. | Experimental | Vaccine 1: TIV. Vaccine 2: LAIV. Receives: Biological: FluMist; Biological: Fluzone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of post-dose 2 HAI (Hemagglutination Inhibition) antibodies to each of the 3 strains of influenza contained in the vaccine.
Measured: Blood sample taken on day 0, 28 + 7, day 60 +/- 4.
Safety assessment of each of the vaccines in combination vaccine.
Measured: Duration of study.
Secondary outcomes (3)
Assessment of secretory IgA in nasal wash samples manifested after 1 or 2 doses of vaccine.
Measured: Nasal wash samples will be colllected on Days 0, 30, and 60.
CMI
Measured: Blood sample taken on Day 0, Day 28 + 7, Day 60 +/- 4.
Post-dose 1 HAI (Hemagglutination Inhibition) antibody titers and viral shedding.
Measured: Day 3 to 5 post LAIV vaccination.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2005 (estimated)
- Study startSep 2005
- Primary completionMar 2007
- Study completionMar 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)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
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00231907
- Sponsor's protocol ID
- 04-101
- Status last verified
- Feb 2010
- First submitted
- 30 Sep 2005
- Last updated
- 27 Aug 2010
- Results posted
- No
Publications
Hoft DF, Babusis E, Worku S, Spencer CT, Lottenbach K, Truscott SM, Abate G, Sakala IG, Edwards KM, Creech CB, Gerber MA, Bernstein DI, Newman F, Graham I, Anderson EL, Belshe RB. Live and inactivated influenza vaccines induce similar humoral responses, but only live vaccines induce diverse T-cell responses in young children. J Infect Dis. 2011 Sep 15;204(6):845-53. doi: 10.1093/infdis/jir436. Epub 2011 Aug 15.
PubMed 21846636
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Influenza Vaccines: Mix and Match of Trivalent Inactivated Influenza (TIV) and Live Attenuated Influenza Vaccine (LAIV), a Phase I Safety, Immunogenicity, and Viral Shedding Study
- ClinicalTrials.gov ID
- NCT00231907
- Acronym / sponsor ID
- 04-101
- Conditions
- Influenza
- Keywords
- influenza, vaccine, TIV, LAIV, booster, children
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Sep 2005
- Primary completion
- Mar 2007 (actual)
- Study completion
- Mar 2007 (actual)
- First posted
- 4 Oct 2005 (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 research is to compare the safety and ability to stimulate antibodies (part of the bodies proteins that fight infections) of two influenza (flu) vaccines given to children 12 to 35 months old. The two flu vaccines being compared are: trivalent inactivated influenza virus vaccine (TIV), a killed virus vaccine given as a shot licensed for use in children 6 months of age or older and live attenuated influenza vaccine (LAIV), a live (but weakened) virus vaccine licensed for children 5 years old and older given as a nose spray. The strains of the viruses have been weakened so that they do not cause typical influenza illness, but may allow the body to develop protection against the flu. LAIV vaccine is not licensed for children less than five years of age, therefore its use in this study is investigational. Participation is approximately 7 months in duration.
Detailed description
This multi-site study is a phase I, open-label, 4-arm trial to evaluate 2 doses of influenza vaccine separated by 30 days. The vaccine will either be two doses of a single vaccine or a combination of vaccine products. FluMist®, a cold-adapted live attenuated influenza vaccine (LAIV), will be administered intranasally via spray applicator. Administration of FluMist in children less than 5 years of age is investigational. FluZone®, a trivalent inactivated influenza vaccine (TIV) licensed for use in children 6 months of age or older, will be administered intramuscularly (IM) to the anterolateral thigh muscle or deltoid muscle. Healthy children, ages 12 to 35 months old, who are representative of the population base of the vaccinating recruitment area, will be enrolled in this study at 3 sites. The primary study objective is to compare the safety and immunogenicity of two doses of licensed TIV or two doses of licensed LAIV with the safety and immunogenicity of a single dose of LAIV that is boosted with a dose of TIV versus children who receive an initial dose of TIV followed by a booster dose of LAIV among children 12 to 35 months of age. The secondary objective is to develop preliminary safety data on these combined vaccine regimes, and to evaluate the possibility that a single dose of TIV will either reduce the potential common side effects of LAIV or reduce the viral shedding associated with LAIV in children and to evaluate LAIV as a "primary" dose vaccine and TIV as a "booster vaccine" for inducing serum Hemagglutination Inhibition (HAI) antibodies. Vaccinees will be followed post-vaccination for safety, reactogenicity and immunogenicity. Patterns of viral shedding will be assessed 4 days after vaccination with LAIV. A final 6-month post-dose two vaccination contact will be made for serious adverse event data collection. Specifically, the investigators will assess the ability of LAIV to prime for a secondary immune response when TIV is given as a booster vaccine, and the investigators will evaluate TIV as a priming event for LAIV booster vaccine. Control groups will include TIV/TIV and LAIV/LAIV groups. The primary outcome measures for the study will be: assessment of post-dose 2 hemagglutination inhibition (HAI) antibodies to each of the 3 strains of influenza contained in the vaccine, safety assessment of each of the vaccines in combination vaccine. The secondary outcome measures include post-dose 1 HAI antibody titers and viral shedding after intranasal vaccination with live attenuated influenza vaccine. An additional secondary outcome will be assessment of secretory Immunoglobulin (Ig) A in nasal wash samples manifested after 1 or 2 doses of vaccine. An additional outcome will be Cell Mediated Immunity after 1 or 2 doses of vaccine. Blood will be collected on days 0, 30 and 60 for antibody detection. Nasal washes will be collected on day 0, 30 and 60 for secretory antibody measurements. A throat and nose swab sample will be collected on day 3 to 5 post LAIV vaccination to assess viral shedding and as dictated by presence of illness symptoms for viral culturing for two weeks after each dose of either LAIV or TIV vaccine. Up to 20 eligible participants will be enrolled in each of the 4 vaccination groups. As a four-arm trial with only active vaccine being administered by two different dosing routes, there will be no blinding to study assignment. Study duration is up to 3 years and individual participant duration is approximately 7 months.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Vaccine 1: TIV. Vaccine 2: TIV. | Active comparator | Biological: FluzoneVaccine 1: TIV. Vaccine 2: TIV. |
| Vaccine 1: LAIV. Vaccine 2: TIV. | Experimental | Biological: FluMist, Biological: FluzoneVaccine 1: LAIV. Vaccine 2: TIV. |
| Vaccine 1: LAIV. Vaccine 2: LAIV. | Experimental | Biological: FluMistVaccine 1: LAIV. Vaccine 2: LAIV. |
| Vaccine 1: TIV. Vaccine 2: LAIV. | Experimental | Biological: FluMist, Biological: FluzoneVaccine 1: TIV. Vaccine 2: LAIV. |
Who may qualify
- Ages
- 12 to 35 months
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Twelve to 35 months of age at enrollment.
- Minimum weight of 8 kg.
- In good health, as determined by parent/guardian verbal medical history and physical examination by clinical investigator.
- Parent/guardian available by telephone for safety data collection through 6 months post-dose 2.
- Ability of parent/guardian to understand and comply with the requirements of the protocol.
Key exclusion criteria (16 listed)
- History of hypersensitivity to any component of LAIV or TIV, including egg or egg products.
- History of hypersensitivity to gentamicin.
- Known or suspected immune deficiency diseases or immunosuppressed or have altered or compromised immune status as a consequence of treatment with immunosuppressive therapies.
- Known close contact with a severely immunocompromised person, such as someone currently in isolation secondary to a bone marrow transplantation (LAIV recipients should avoid close contact with severely immunocompromised individuals for at least 7 days after vaccination).
- History of chronic underlying medical conditions such as chronic disorders of the cardiovascular and pulmonary systems, chronic metabolic diseases (including diabetes), renal dysfunction, or hemoglobinopathies.
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 |
|---|---|---|
| FluMistLive attenuated influenza vaccine (LAIV) containing approximately 10^7 TCID50 of each of the 3 influenza strains. 0.5 mL total dose volume administered intranasally via spray applicator (approximately 0.25 mL into each nostril). Administration of Flumist in children under 5 years of age is investigational. | Biological | Vaccine 1: LAIV. Vaccine 2: LAIV., Vaccine 1: LAIV. Vaccine 2: TIV., Vaccine 1: TIV. Vaccine 2: LAIV. |
| FluzoneTrivalent inactivated vaccine (TIV), licensed Fluzone preservative free pediatric dose, 0.25 mL administered intramuscularly to the anterolateral thigh muscle or deltoid muscle. | Biological | Vaccine 1: LAIV. Vaccine 2: TIV., Vaccine 1: TIV. Vaccine 2: LAIV., Vaccine 1: TIV. Vaccine 2: TIV. |
Primary outcome
Assessment of post-dose 2 HAI (Hemagglutination Inhibition) antibodies to each of the 3 strains of influenza contained in the vaccine.
Time frame: Blood sample taken on day 0, 28 + 7, day 60 +/- 4.
Safety assessment of each of the vaccines in combination vaccine.
Time frame: Duration of study.
3 secondary outcomes
Assessment of secretory IgA in nasal wash samples manifested after 1 or 2 doses of vaccine.
Time frame: Nasal wash samples will be colllected on Days 0, 30, and 60.
CMI
Time frame: Blood sample taken on Day 0, Day 28 + 7, Day 60 +/- 4.
Post-dose 1 HAI (Hemagglutination Inhibition) antibody titers and viral shedding.
Time frame: Day 3 to 5 post LAIV vaccination.
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 27 Aug 2010.
- Derived from this study: PubMed 21846636Hoft DF, Babusis E, Worku S, Spencer CT, Lottenbach K, Truscott SM, Abate G, Sakala IG, Edwards KM, Creech CB, Gerber MA, Bernstein DI, Newman F, Graham I, Anderson EL, Belshe RB. Live and inactivated influenza vaccines induce similar humoral responses, but only live vaccines induce diverse T-cell responses in young children. J Infect Dis. 2011 Sep 15;204(6):845-53. doi: 10.1093/infdis/jir436. Epub 2011 Aug 15.
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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.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing FluMist and Fluzone in people with Influenza, run by National Institute of Allergy and Infectious Diseases (NIAID) at 3 sites 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 6 inclusion and 16 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 27 Aug 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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?
Assessment of post-dose 2 HAI (Hemagglutination Inhibition) antibodies to each of the 3 strains of influenza contained in the vaccine. (time frame: Blood sample taken on day 0, 28 + 7, day 60 +/- 4.). 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 NCT00231907, which also lists 1 linked publication.
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 27 Aug 2010.