InfluenzaPhase 4NCT01816464
Immunogenicity and Safety of Trivalent Influenza Vaccine in Pregnant and Nonpregnant HIV Uninfected Women
A Phase 4 study testing Trivalent Influenza Vaccine in people with Influenza, run by University of Witwatersrand, South Africa at 1 site in South Africa.
Trial summary
The overall aim of this project is to evaluate the immunogenicity of TIV vaccination in HIV-uninfected pregnant women compared with HIV-uninfected non-pregnant women in 2013. Safety data will also be collected.THe Pregnancy outcomes and the transplacental transfer of antibodies will also be assessed. Read more about this study
- Who is it for?
- Ages 18 to 39 years, women only
- Conditions the study is for
- Influenza
- What is being tested?
- Trivalent Influenza Vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 1 siteSouth Africa
- Study dates
- Sep 2013to Apr 2014
- Phase
- Phase 4
- 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 39 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Documented to be HIV-1 uninfected on one assay used in the Prevention of Mother to Child Transmission (PMTCT)/ other program undertaken within 12 weeks of study enrolment.
- Able to understand and comply with planned study procedures. (iii) Provides written informed consent prior to initiation of study. (iv) Women age ≥ 18 years to < 39 years.
- Gestational age ≥20 weeks to <36 weeks documented by the approximate date of the last menstrual period and corroborated by physical exam and sonar report if available.
Who cannot join
- Receipt of TIV, other than through the study, during the current influenza season documented by medical history or record.
- Receipt of any live licensed vaccine ≤ 28 days or any other vaccine (except for tetanus toxoid vaccine) ≤ 14 days prior to study-vaccine.
- Receipt of a non-licensed agent (vaccine, drug, biologic, device, blood product, or medication) ≤ 28 days prior to vaccination in this study, or expects to receive another non-licensed agent before delivery unless study approval is obtained.
- Any significant (in the opinion of the site investigator) acute illness and/or oral temperature greater than or equal to 38 degrees C ≤ 24 hours prior to study entry.
- Use of anti-cancer systemic chemotherapy or radiation therapy ≤ 48 weeks of study enrollment, or has immunosuppression as a result of an underlying illness or treatment.
- Long term use of glucocorticoids, including oral or parenteral prednisone ≥ 20 mg/day or equivalent for more than 2 consecutive weeks (or 2 weeks total) ≤ 12 weeks of study entry, or high-dose inhaled steroids (>800 mcg/day of beclomethasone dipropionate or equivalent) ≤ 12 weeks before study entry (nasal and topical steroids are allowed).
Show all 10Show fewer
- Receipt of immunoglobulin or other blood products (with exception of Rho D immune globulin) ≤ 12 weeks prior to enrollment in this study or is scheduled to receive immunoglobulin or other blood products (with the exception of Rho D immune globulin) during pregnancy or for the first 24 weeks after delivery.
- Receipt of immune mediators ≤ 12 weeks before enrollment. (ix) Uncontrolled major psychiatric disorder. (x) History of a severe adverse reaction to previous TIV. (xi) Any condition that would, in the opinion of the site investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol.
- Receipt of corticosteroids for preterm labor ≤ 14 days before study entry. (ii) Pregnancy complications (in the current pregnancy) such as pre-term labor, hypertension (Blood Pressure (BP) >140/90 in the presence of proteinuria or BP >150/100, with or without proteinuria or currently on antihypertensive medication) or pre-eclampsia.
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Trial locations and contacts
1 site in 1 country.
About this study
Official title: Immunogenicity and Safety of Trivalent Influenza Vaccine in Pregnant and Non-pregnant HIV-Uninfected Women: An Open Label Trial
The overall aim of this project is to evaluate the immunogenicity of TIV vaccination in HIV-uninfected pregnant women compared with HIV-uninfected non-pregnant women in 2013. Safety data will also be collected.THe Pregnancy outcomes and the transplacental transfer of antibodies will also be assessed.
- Conditions
- Influenza
- Being tested
- Trivalent Influenza Vaccine
- Keywords
- Influenza, Vaccination
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trivalent Influenza VaccineBiological
Also called Vaxigrip
The formulation based on the WHO recommendation for influenza vaccines for 2013 for the Southern-hemisphere included the following vaccine strains:
- an A/California/7/2009 (H1N1)pdm09-like virus;
- an A/Victoria/361/2011 (H3N2)-like virus; - a B/Wisconsin/1/2010-like virus.
The vaccine to be used in the study in 2013 is Vaxigrip (Sanofi Pasteur), or other equivalent licensed vaccine should the latter not be available, which will be procured commercially in pre-filled syringes. Using aseptic technique, participants will be injected with 0.5 mL of TIV from pre-filled syringe.
| Study group | Role | What they receive |
|---|---|---|
| Trivalent Influenza Vaccine | Experimental | The formulation based on the WHO recommendation for influenza vaccines for 2013 for the Southern-hemisphere included the following vaccine strains:
* an A/California/7/2009 (H1N1)pdm09-like virus;
* an A/Victoria/361/2011 (H3N2)-like virus;
* a B/Wisconsin/1/2010-like virus.
Dose: Single Dose 0.5 mL of TIV from pre-filled syringe. Receives: Biological: Trivalent Influenza Vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Compare the immunogenicity of Trivalent Influenza Vaccine (TIV) in pregnant compared to non-pregnant Human Immunodeficiency Virus (HIV)-uninfected women.
Hemagglutination inhibition assays (HAI)will be performed to assess the immunogenicity of TIV. In this study we will use the following definitions to assess the humoral immune response to TIV: HAI titers <1:10 = seronegative; HAI titers ≥1:10 = seropositive; HAI titers ≥1:40 = sero-protective titers; and sero-conversion will be defined as HAI titers from <1:10 to ≥1:40 or ≥4-fold increase if pre-vaccination titers were ≥1:10.
Measured: one month post-vaccination
Evaluate the immunogenicity of Trivalent Influenza Vaccine (TIV) in pregnant Human Immunodeficiency Virus (HIV)-uninfected women at time of delivery
Hemagglutination inhibition assays (HAI)will be performed to assess the immunogenicity of TIV. In this study we will use the following definitions to assess the humoral immune response to TIV: HAI titers <1:10 = seronegative; HAI titers ≥1:10 = seropositive; HAI titers ≥1:40 = sero-protective titers; and sero-conversion will be defined as HAI titers from <1:10 to ≥1:40 or ≥4-fold increase if pre-vaccination titers were ≥1:10.
Measured: one week post delivery for the pregnant cohort
Secondary outcomes (7)
Determine the impact of vaccination on T-cell activation and regulatory B and T cells subpopulations in pregnant and non-pregnant women.
T-lymphocyte activation assays will be performed using state-of-the art polychromatic flow cytometry. The T- and B-cell phenotypes are assessed by flow cytometry using freshly thawed Peripheral Blood Mononuclear Cells (PBMC). Cells are stained using monoclonal antibodies against the comparator molecules
Measured: one month post vaccination and one week post delivery in pregnant cohort
2.2.2. Determine the impact of vaccination on cell-mediated immune responses to each influenza strain in HIV-uninfected pregnant and non-pregnant women
Interferon (IFN)- Enzyme Linked Immuno Spot (ELISPOT) responses will be assessed on fresh PBMCs. PBMCs will be separated and stimulated with influenza virus corresponding to the vaccine strains.Spots will be visualized with a ELISPOT plate reader. Results will be reported as Spot Forming Cells (SFC) /106 PBMCs.
Measured: one month post vaccination
Determine the dynamics of transplacental transfer of maternal Hemagglutinin (HA) antibodies to their newborns.
The study will assess the effect of TIV administration during pregnancy on transplacental influenza-specific antibody transfer to the fetus. HAI titers will be measured in infants within one week of birth. Using the 1:40 HAI titer as a defining threshold of protection against wild type influenza, we will determine the proportion of infants protected against influenza at birth.
Measured: one week post delivery in pregnant cohort
Determine antibodies against TIV present in breast milk
Influenza specific antibodies measures by HAI titres in the breastmilk will be measured. Mothers will express breastmilk into sterile containers to collect the samples.
Measured: in week post delivery
Compare local and systemic solicited reactions to TIV in pregnant and non-pregnant HIV-uninfected women.
Participants will remain in the clinic for at least 30 minutes after vaccination so that clinic personnel can observe for any potential adverse reactions to the vaccine.
Report of vaccine-related local (redness, swelling, tenderness, itching,) and systemic (fever, malaise, myalgia, nausea, headache, rash) adverse events will be solicited at day 7 and day 28 by means of a participant diary card. Serious Adverse Events (SAEs) will be reported.
Measured: one month post vaccination
Describe safety outcome measures (maternal and foetal) of TIV-vaccination of HIV-uninfected pregnant women.
Safety and tolerability of the study vaccine will be monitored by means of Adverse Events (AEs) and toxicity reports presenting laboratory and clinical data. The data to be reviewed by the protocol team will be pooled across treatment arms.In addition to monthly toxicity reviews by the Core Team, the study will be monitored by a Safety Monitoring Committee (SMC). The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events is used
Measured: one month post vaccination and one week post delivery in pregnant cohort
Describe obstetric outcomes in HIV-uninfected pregnant women who received TIV
Data will be collected from birth records including low birth weight (<2 500 g), premature delivery (<37 weeks), emergency caesarean section
Measured: one week post delivery in pregnant cohort
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2013 (estimated)
- Study startSep 2013
- Primary completionFeb 2014
- Study completionApr 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for InfluenzaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Witwatersrand, South Africa
- Sponsor type
- University, hospital or other
- Collaborators
- Bill and Melinda Gates Foundation
- Responsible party
- Principal investigator, Michelle Groome, University of Witwatersrand, South Africa
- Investigators
- Shabir A Madhi, PHD, Principal investigator, University of Witwatersrand, South Africa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01816464
- Sponsor's protocol ID
- MatFlu_HIVneg_preg+nonpreg
- Status last verified
- Jan 2015
- First submitted
- 14 Mar 2013
- Last updated
- 12 Jan 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immunogenicity and Safety of Trivalent Influenza Vaccine in Pregnant and Non-pregnant HIV-Uninfected Women: An Open Label Trial
- ClinicalTrials.gov ID
- NCT01816464
- Acronym / sponsor ID
- MatFlu_HIVneg_preg+nonpreg
- Conditions
- Influenza
- Keywords
- Influenza, Vaccination
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 150 participants (actual)
- Lead sponsor
- University of Witwatersrand, South AfricaUniversity, hospital or other
- Collaborators
- Bill and Melinda Gates Foundation
- Study start
- Sep 2013
- Primary completion
- Feb 2014 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 22 Mar 2013 (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 overall aim of this project is to evaluate the immunogenicity of TIV vaccination in HIV-uninfected pregnant women compared with HIV-uninfected non-pregnant women in 2013. Safety data will also be collected.THe Pregnancy outcomes and the transplacental transfer of antibodies will also be assessed.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Trivalent Influenza Vaccine | Experimental | Biological: Trivalent Influenza VaccineThe formulation based on the WHO recommendation for influenza vaccines for 2013 for the Southern-hemisphere included the following vaccine strains: * an A/California/7/2009 (H1N1)pdm09-like virus; * an A/Victoria/361/2011 (H3N2)-like virus; * a B/Wisconsin/1/2010-like virus. Dose: Single Dose 0.5 mL of TIV from pre-filled syringe. |
Who may qualify
- Ages
- 18 to 39 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Documented to be HIV-1 uninfected on one assay used in the Prevention of Mother to Child Transmission (PMTCT)/ other program undertaken within 12 weeks of study enrolment.
- Able to understand and comply with planned study procedures. (iii) Provides written informed consent prior to initiation of study. (iv) Women age ≥ 18 years to < 39 years.
- Gestational age ≥20 weeks to <36 weeks documented by the approximate date of the last menstrual period and corroborated by physical exam and sonar report if available.
Key exclusion criteria (10 listed)
- Receipt of TIV, other than through the study, during the current influenza season documented by medical history or record.
- Receipt of any live licensed vaccine ≤ 28 days or any other vaccine (except for tetanus toxoid vaccine) ≤ 14 days prior to study-vaccine.
- Receipt of a non-licensed agent (vaccine, drug, biologic, device, blood product, or medication) ≤ 28 days prior to vaccination in this study, or expects to receive another non-licensed agent before delivery unless study approval is obtained.
- Any significant (in the opinion of the site investigator) acute illness and/or oral temperature greater than or equal to 38 degrees C ≤ 24 hours prior to study entry.
- Use of anti-cancer systemic chemotherapy or radiation therapy ≤ 48 weeks of study enrollment, or has immunosuppression as a result of an underlying illness or treatment.
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 |
|---|---|---|
| Trivalent Influenza VaccineAlso: VaxigripThe formulation based on the WHO recommendation for influenza vaccines for 2013 for the Southern-hemisphere included the following vaccine strains: * an A/California/7/2009 (H1N1)pdm09-like virus; * an A/Victoria/361/2011 (H3N2)-like virus; - a B/Wisconsin/1/2010-like virus. The vaccine to be used in the study in 2013 is Vaxigrip (Sanofi Pasteur), or other equivalent licensed vaccine should the latter not be available, which will be procured commercially in pre-filled syringes. Using aseptic technique, participants will be injected with 0.5 mL of TIV from pre-filled syringe. | Biological | Trivalent Influenza Vaccine |
Primary outcome
Compare the immunogenicity of Trivalent Influenza Vaccine (TIV) in pregnant compared to non-pregnant Human Immunodeficiency Virus (HIV)-uninfected women.
Time frame: one month post-vaccination
Hemagglutination inhibition assays (HAI)will be performed to assess the immunogenicity of TIV. In this study we will use the following definitions to assess the humoral immune response to TIV: HAI titers <1:10 = seronegative; HAI titers ≥1:10 = seropositive; HAI titers ≥1:40 = sero-protective titers; and sero-conversion will be defined as HAI titers from <1:10 to ≥1:40 or ≥4-fold increase if pre-vaccination titers were ≥1:10.
Evaluate the immunogenicity of Trivalent Influenza Vaccine (TIV) in pregnant Human Immunodeficiency Virus (HIV)-uninfected women at time of delivery
Time frame: one week post delivery for the pregnant cohort
Hemagglutination inhibition assays (HAI)will be performed to assess the immunogenicity of TIV. In this study we will use the following definitions to assess the humoral immune response to TIV: HAI titers <1:10 = seronegative; HAI titers ≥1:10 = seropositive; HAI titers ≥1:40 = sero-protective titers; and sero-conversion will be defined as HAI titers from <1:10 to ≥1:40 or ≥4-fold increase if pre-vaccination titers were ≥1:10.
7 secondary outcomes
Determine the impact of vaccination on T-cell activation and regulatory B and T cells subpopulations in pregnant and non-pregnant women.
Time frame: one month post vaccination and one week post delivery in pregnant cohort
2.2.2. Determine the impact of vaccination on cell-mediated immune responses to each influenza strain in HIV-uninfected pregnant and non-pregnant women
Time frame: one month post vaccination
Determine the dynamics of transplacental transfer of maternal Hemagglutinin (HA) antibodies to their newborns.
Time frame: one week post delivery in pregnant cohort
Determine antibodies against TIV present in breast milk
Time frame: in week post delivery
Compare local and systemic solicited reactions to TIV in pregnant and non-pregnant HIV-uninfected women.
Time frame: one month post vaccination
Describe safety outcome measures (maternal and foetal) of TIV-vaccination of HIV-uninfected pregnant women.
Time frame: one month post vaccination and one week post delivery in pregnant cohort
Describe obstetric outcomes in HIV-uninfected pregnant women who received TIV
Time frame: one week post delivery in pregnant cohort
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 12 Jan 2015.
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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.
Shabir A Madhi, PHD principal investigator
University of Witwatersrand, South Africa
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Trivalent Influenza Vaccine in people with Influenza, run by University of Witwatersrand, South Africa at 1 site in South Africa.
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 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Jan 2015. 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 South Africa. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
Compare the immunogenicity of Trivalent Influenza Vaccine (TIV) in pregnant compared to non-pregnant Human Immunodeficiency Virus (HIV)-uninfected women. (time frame: one month post-vaccination). 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?
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 12 Jan 2015.