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

NCT01527825 | Completed Phase 3 DMC

• 1 other identifier: MatfluHIVpos_3dosingschedule
• Study Type: interventional
• Target: 800
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Influenza

Outcome Measures

Primary Outcomes (3)

• Number of participants who mount an adequate immune response one month post vaccination to a double dose compared to single dose of TIV

  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.

  One month (28-35 days) post vaccination

• 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

  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.

  One month (28-35 days) post vaccination

• Number of participants in each treatment arm who have local and/ or systemic reactions post vaccination with TIV

  Evaluate the safety of the three dosing schedules of TIV in HIV-infected pregnant women vaccinated between 12-36 weeks of gestational age.

  One week post vaccination

Secondary Outcomes (9)

• 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.

  Within first week of life (0-7 days)

• Number of infants with protective maternal antibody levels against TIV at birth and at 8, 16 and 24 weeks of age

  Birth to 24 weeks post delivery

• 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

  Birth to 24 weeks

• 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

  Birth to 24 weeks post delivery

• Number of women protected against laboratory confirmed influenza in each treatment arm

  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.

Study Arms (3)

Single dose

ACTIVE COMPARATOR

Trivalent Influenza Vaccine (seasonal)

Biological: Trivalent influenza vaccine (seasonal); Biological: Normal saline

Double dose TIV

EXPERIMENTAL

Trivalent Influenza vaccine (seasonal) Two doses will be administered at enrolment

Biological: Trivalent influenza vaccine (seasonal); Biological: Normal saline

Two dose TIV

EXPERIMENTAL

Trivalent Influenza vaccine (seasonal) Participants will receive two doses of TIV, one month apart

Biological: Trivalent influenza vaccine (seasonal); Biological: Normal saline

Interventions

Trivalent influenza vaccine (seasonal) BIOLOGICAL

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.

Also known as: Vaxigrip

Double dose TIV; Single dose; Two dose TIV

Normal saline BIOLOGICAL

0.5ml normal saline will be used as 'placebo' vaccine to maintain blinding

Also known as: NaCl

Double dose TIV; Single dose; Two dose TIV

Eligibility Criteria

• Age: 18 Years - 39 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Witwatersrand, South Africa: lead

Study Sites (1)

Respiratory and Meningeal Pathogens research unit

Soweto, Johannesburg, Gauteng, 2013, South Africa

Location

Related Publications (1)

• Nunes MC, Cutland CL, Moultrie A, Jones S, Ortiz JR, Neuzil KM, Klugman KP, Simoes EAF, Weinberg A, Madhi SA; Maternal Flu Trial Team. Immunogenicity and safety of different dosing schedules of trivalent inactivated influenza vaccine in pregnant women with HIV: a randomised controlled trial. Lancet HIV. 2020 Feb;7(2):e91-e103. doi: 10.1016/S2352-3018(19)30322-4. Epub 2020 Jan 3.

  PMID: 31911146 DERIVED

MeSH Terms

Conditions

Influenza, Human

Interventions

Influenza Vaccines; vaxigrip; Saline Solution

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Shabir A Madhi, MD PhD

  University of Witwatersrand, South Africa

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior medical officer

Study Record Dates

• First Submitted: December 14, 2011
• First Posted: February 7, 2012
• Study Start: September 1, 2012
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: January 12, 2015

Record last verified: 2015-01

Locations

ZA (1)