Immunogenicity and Safety of Different Dosing Schedules of Trivalent Influenza Vaccine in HIV-infected Pregnant Women

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Michelle Groome, University of Witwatersrand, South Africa
ClinicalTrials.gov Identifier:
NCT01527825
First received: December 14, 2011
Last updated: December 10, 2013
Last verified: December 2013
  Purpose

The overall aim of this project is to evaluate the safety and immunogenicity of 3 different dosing options of trivalent influenza vaccine (TIV) vaccination of HIV-infected pregnant women: single dose, double dose (at same time point) and two-doses (1 month apart).


Condition Intervention Phase
Influenza
Biological: Trivalent influenza vaccine (seasonal)
Biological: Normal saline
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Immunogenicity and Safety of Different Dosing Schedules of Trivalent Influenza Vaccine in HIV-infected Pregnant Women: a Randomized Controlled Trial

Resource links provided by NLM:


Further study details as provided by University of Witwatersrand, South Africa:

Primary Outcome Measures:
  • Number of participants who mount an adequate immune response one month post vaccination to a double dose compared to single dose of TIV [ Time Frame: One month (28-35 days) post vaccination ] [ Designated as safety issue: No ]
    Determine the sero-response rate to each of the vaccine viral strains, defined as post vaccination hemagglutination inhibition (HAI) levels of ≥1:40 AND ≥4 fold increase over baseline HAI levels, in HIV-infected pregnant women receiving a double strength TIV dose compared to mothers receiving a single dose of TIV one-month after completion of the dosing schedule.

  • Number of participants who mount an adequate immune response one month post completing vaccination to two-dose TIV administered 1 month apart, compared to single dose TIV [ Time Frame: One month (28-35 days) post vaccination ] [ Designated as safety issue: No ]
    Determine the sero-response rate to each of the vaccine viral strains, defined as post vaccination HAI levels of ≥1:40 AND ≥4 fold increase over baseline HAI levels, in HIV-infected pregnant women receiving two-doses of TIV spaced 21-35 days apart compared to women receiving a single dose of TIV one-month after completion of the dosing schedule.

  • Number of participants in each treatment arm who have local and/ or systemic reactions post vaccination with TIV [ Time Frame: One week post vaccination ] [ Designated as safety issue: Yes ]
    Evaluate the safety of the three dosing schedules of TIV in HIV-infected pregnant women vaccinated between 12-36 weeks of gestational age.


Secondary Outcome Measures:
  • Number of infants born to mothers who received double- or two doses of TIV who are seroprotected against influenza compared to infants born to mothers in single dose arm. [ Time Frame: Within first week of life (0-7 days) ] [ Designated as safety issue: No ]
    Compare the proportion of newborns born to HIV-infected mothers in the double dose and two-dose arms with HAI antibody titers of ≥1:40 to each of the three TIV strains to newborns of HIV-infected and HIV-uninfected women (enrolled in separate parallel cohort) who received single dose of TIV.

  • Number of infants with protective maternal antibody levels against TIV at birth and at 8, 16 and 24 weeks of age [ Time Frame: Birth to 24 weeks post delivery ] [ Designated as safety issue: No ]
    Determine the kinetics of transplacental transfer of maternal Hemagglutinin (HA) antibodies and persistence thereof until 24 weeks post-partum in the infants.

  • Number of infants born to women in double- and two dose TIV arms, compared to single TIV dose arm who are protected against laboratory confirmed influenza [ Time Frame: Birth to 24 weeks ] [ Designated as safety issue: No ]
    Compare the relative efficacy of a double-strength or two-dose dose TIV schedule compared to a single dose TIV schedule in pregnant HIV-infected women in protecting against laboratory-confirmed influenza illness in their infants up to 24 weeks of chronological age.

  • Number of infants born to women in double- and two- dose TIV arms compared to single dose arm who are protected against clinical influenza like illness [ Time Frame: Birth to 24 weeks post delivery ] [ Designated as safety issue: No ]
    Compare the relative efficacy of a double-strength or two-dose dose TIV schedule compared to a single dose TIV schedule in pregnant HIV-infected women in protecting against protocol defined clinical influenza like illness (ILI) in their infants up to 24 weeks of chronological age.

  • Number of women protected against laboratory confirmed influenza in each treatment arm [ Time Frame: From date of vaccination (12 to 36 weeks gestational age [GA]) until infant is 24 weeks old. Anticipated mean GA at randomisation is 20 weeks, and at delivery is 39 weeks, so average follow up period is 43 weeks, however it could be as long as a year. ] [ Designated as safety issue: No ]
    Compare the relative efficacy of a double-strength or two-dose dose TIV schedule compared to a single dose TIV schedule in pregnant HIV-infected women in protecting against laboratory-confirmed influenza illness in maternal participants up to 24 weeks post partum.

  • Number of women protected against clinical influenza like illness in each treatment arm [ Time Frame: From date of vaccination (12 to 36 weeks gestational age [GA]) until infant is 24 weeks old. Anticipated mean GA at randomisation is 20 weeks, and at delivery is 39 weeks, so average follow up period is 43 weeks, however it could be as long as a year. ] [ Designated as safety issue: No ]
    Compare the relative efficacy of a double-strength or two-dose dose TIV schedule compared to a single dose TIV schedule in pregnant HIV-infected women in protecting against protocol defined clinical ILI in maternal participants up to 24 weeks post partum.

  • Number of women who mount immune responses (seroconversion /seroprotection)in each treatment arm [ Time Frame: From date of vaccination (12 to 36 weeks gestational age [GA]) until infant is 24 weeks old. Anticipated mean GA at randomisation is 20 weeks, and at delivery is 39 weeks, so average follow up period is 43 weeks, however it could be as long as a year. ] [ Designated as safety issue: No ]
    Define and compare cell mediated immune responses to different dosing options of TIV in HIV-infected pregnant women.

  • Number of women who have changes to CD4+ and/ or viral load results post vaccination in each treatment arm [ Time Frame: From date of vaccination (12 to 36 weeks gestational age [GA]) until infant is born. Anticipated mean GA at randomisation is 20 weeks, and at delivery is 39 weeks, so average follow up period is 19 weeks, however it could be as long as 30 weeks. ] [ Designated as safety issue: Yes ]
    Evaluate the effect of TIV (single, double and two doses) on CD4+ cell count and HIV-viral load changes comparing baseline levels to levels at delivery.

  • Number of participants in each treatment arm who suffer adverse pregnancy outcomes (maternal or foetal) after TIV-vaccination [ Time Frame: From date of vaccination (12 to 36 weeks gestational age [GA]) until infant is born. Anticipated mean GA at randomisation is 20 weeks, and at delivery is 39 weeks, so average follow up period is 19 weeks, however it could be as long as 30 weeks. ] [ Designated as safety issue: Yes ]
    Describe safety outcome measures (maternal and foetal) of TIV-vaccination of HIV-infected pregnant women


Estimated Enrollment: 789
Study Start Date: September 2012
Estimated Study Completion Date: May 2014
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Single dose
Trivalent Influenza Vaccine (seasonal)
Biological: Trivalent influenza vaccine (seasonal)

Single 0.5ml dose of Southern hemisphere 2012 TIV, formulation containing:

  • An A/California/7/2009 (H1N1)pdm-like virus
  • An A/Perth/16/2009 (H3N2)-like virus*
  • A B/Brisbane/60/2008-like virus * A/Wisconsin/15/2009 and A/Victoria/210/2009 are A/Perth/16/2009-like viruses for use in the 2012 Southern Hemisphere winter. This vaccine is the same as the vaccine used for the 2011 Southern hemisphere influenza season.
Other Name: Vaxigrip
Biological: Normal saline
0.5ml normal saline will be used as 'placebo' vaccine to maintain blinding
Other Name: NaCl
Experimental: Double dose TIV
Trivalent Influenza vaccine (seasonal) Two doses will be administered at enrolment
Biological: Trivalent influenza vaccine (seasonal)

Single 0.5ml dose of Southern hemisphere 2012 TIV, formulation containing:

  • An A/California/7/2009 (H1N1)pdm-like virus
  • An A/Perth/16/2009 (H3N2)-like virus*
  • A B/Brisbane/60/2008-like virus * A/Wisconsin/15/2009 and A/Victoria/210/2009 are A/Perth/16/2009-like viruses for use in the 2012 Southern Hemisphere winter. This vaccine is the same as the vaccine used for the 2011 Southern hemisphere influenza season.
Other Name: Vaxigrip
Biological: Normal saline
0.5ml normal saline will be used as 'placebo' vaccine to maintain blinding
Other Name: NaCl
Experimental: Two dose TIV
Trivalent Influenza vaccine (seasonal) Participants will receive two doses of TIV, one month apart
Biological: Trivalent influenza vaccine (seasonal)

Single 0.5ml dose of Southern hemisphere 2012 TIV, formulation containing:

  • An A/California/7/2009 (H1N1)pdm-like virus
  • An A/Perth/16/2009 (H3N2)-like virus*
  • A B/Brisbane/60/2008-like virus * A/Wisconsin/15/2009 and A/Victoria/210/2009 are A/Perth/16/2009-like viruses for use in the 2012 Southern Hemisphere winter. This vaccine is the same as the vaccine used for the 2011 Southern hemisphere influenza season.
Other Name: Vaxigrip
Biological: Normal saline
0.5ml normal saline will be used as 'placebo' vaccine to maintain blinding
Other Name: NaCl

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 39 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Pregnant women age under 18 years to under 39 years.
  • Gestational age greater or equal 12 weeks to under 36 weeks documented by the approximate date of the last menstrual period and corroborated by physical/ sonar examination.
  • Documented to be HIV-infected on two assays prior to study-enrolment.
  • Able to understand and comply with planned study procedures.
  • Provides written informed consent prior to initiation of study.

Exclusion Criteria:

  • Features of WHO clinical category 3 or 4 of AIDS at the time of enrolment.
  • 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 less or inactivated licensed vaccine (EXCEPT tetanus toxoid) 14 days or less prior to study-vaccine.
  • Receipt of a non-licensed agent (vaccine, drug, biologic, device, blood product, or medication) 28 days or less 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 Celcius ≤ 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).
  • Receipt of corticosteroids for preterm labor ≤ 14 days before study entry.
  • 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 interleucin 2 (IL2), interferon (IFN), GMCSF or other immune mediators ≤ 12 weeks before enrollment.
  • Uncontrolled major psychiatric disorder.
  • History of a severe adverse reaction to previous TIV.
  • 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.
  • Pregnancy complications (in the current pregnancy) such as pre-term labor, hypertension (BP >140/90 in the presence of proteinuria or BP >150/100, with or without proteinuria or currently on antihypertensive medication) and pre-eclampsia.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01527825

Locations
South Africa
Respiratory and Meningeal Pathogens research unit
Soweto, Johannesburg, Gauteng, South Africa, 2013
Sponsors and Collaborators
University of Witwatersrand, South Africa
Investigators
Study Chair: Shabir A Madhi, MD PhD University of the Witwatersrand
  More Information

No publications provided

Responsible Party: Michelle Groome, Senior medical officer, University of Witwatersrand, South Africa
ClinicalTrials.gov Identifier: NCT01527825     History of Changes
Other Study ID Numbers: MatfluHIVpos_3dosingschedule
Study First Received: December 14, 2011
Last Updated: December 10, 2013
Health Authority: South Africa: Human Research Ethics Committee
South Africa: Medicines Control Council
South Africa: National Health Research Ethics Council

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on September 14, 2014