Influenza Vaccine Trial in HIV Uninfected Pregnant Women

NCT01306669 | Completed Phase 3 DMC

• 1 other identifier: Maternal_flu_HIVneg_101106
• Study Type: interventional
• Target: 2,116
• Locations: 1 country
• Sites: 1

Brief Summary

Randomised, double blind, placebo controlled trial to assess safety, immunogenicity and efficacy of Trivalent Influenza vaccine in HIV uninfected pregnant women

Conditions

Influenza

Outcome Measures

Primary Outcomes (2)

• The number of laboratory-confirmed influenza cases in infants born to mothers who received TIV or placebo will be used to determine efficacy of TIV vaccination of pregnant women against laboratory-confirmed influenza illness in their infants

  All infants (up to 24 weeks of age) born to women enrolled on trial will be assessed by study staff if they have any signs or symptoms (including fever, hospitalisation, apnea, cough, nasal catarrh/ congenstion, tachypnea) which could indicate influenza like illness. Nasopharyngeal aspirate samples collected at illness visits will be processed for viruses using real time reverse transcriptase-polymerase chain reaction (rRTPCR) assays.

  24 weeks of age

• Humoral and cell-mediated immune (CMI) responses to influenza strains in the vaccine will be measured to assess the immunogenicity of TIV in pregnant women vaccinated between 20-34 weeks of gestational age

  Humoral immunity will be measured by hemagglutination inhibition (HAI) assay. Blood will be collected at enrolment (pre-vaccination), one month post vaccination, delivery (+7 days) and 24 weeks post delivery. Humoral immune response definitions: HAI titers \< 1:10 = seronegative; ≥ 1:10 = seropositive; \> 1:40 = protected against influenza; Response to TIV = serconversion (from \<1:10 to ≥1:10) and/or 4-fold increase of HAI titers. Cell mediated immunity will be measured by ELISPOT response to TIV. Blood will be collected at enrollment (pre-vaccination) and one month post vaccination.

  one month post vaccination, delivery (+7 days), 24 weeks post natal

Secondary Outcomes (5)

• Hemagglutinin (HA) antibody measurements in blood taken from mother and infants up to 24 weeks post delivery will be used to assess kinetics of transplacentally acquired antibodies

  Birth (+7 days), 8, 16 & 24 weeks of age

• Clinical influenza like illnesses in infants born to TIV and placebo recipients will be used to assess efficacy of TIV in pregnant women against ILI in their infants

  24 weeks of age

• The number of laboratory-confirmed influenza illnesses in maternal participants during pregnancy and for 24 weeks post-partum will be used to assess efficacy of TIV against laboratory confirmed influenza

  24 weeks post delivery

• The number of maternal participants who have ILI in whom influenza is not isolated from NP or OP swabs will be used to determine efficacy of TIV against clinical ILI in mothers

  24 weeks post delivery

• Infants born to TIV/ placebo recipients will have nasopharyngeal swabs collected at 8, 16 and 24 weeks of age to determine acquisition of pneumococcal carriage

  24 weeks of age

Study Arms (2)

Trivalent influenza vaccine

ACTIVE COMPARATOR

Single dose administration of trivalent influenza vaccine prior to onset of influenza season

Biological: Trivalent influenza vaccine

Normal saline

PLACEBO COMPARATOR

Biological: Normal saline

Interventions

Trivalent influenza vaccine BIOLOGICAL

single dose of 0.5ml of Trivalent influenza vaccine for season will be administered into deltoid muscle of non-dominant arm

Also known as: Vaxigrip

Trivalent influenza vaccine

Normal saline BIOLOGICAL

Single dose of 0.5ml of normal saline will be administered into deltoid muscle of non-dominant arm

Also known as: NaCl

Normal saline

Eligibility Criteria

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

You may qualify if:

• Pregnant women age 18 years to less than 39 years.
• Gestational age greater than or equal to 20 weeks to less than 34 weeks documented by the approximate date of the last menstrual period and corroborated by physical exam.
• Documented to be HIV-1 uninfected on two assays used in the PMTCT program undertaken within 12 weeks of 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:

• 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 less than or equal to 28 days or inactivated licensed vaccine (except for tetanus toxoid vaccine) less than to equal to 14 days prior to study-vaccine.
• Participants in the nested immunogenicity cohort cannot receive ANY vaccine (including tetanus toxoid) within 14 days of the study-vaccine.
• Receipt of a non-licensed agent (vaccine, drug, biologic, device, blood product, or medication) less than or equal to 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).
• 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 IL2, 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 (systolic blood pressure ≥ 140 and/or diastolic blood pressure ≥ 90 mm Hg) and pre-eclampsia.

Sponsors & Collaborators

• University of Witwatersrand, South Africa: lead
• Emory University: collaborator
• University of Colorado, Denver: collaborator
• Bill and Melinda Gates Foundation: collaborator

Study Sites (1)

RMPRU, Chris Hani Baragwanath Hospital

Johannesburg, Gauteng, 2013, South Africa

Location

Related Publications (7)

• Motsoeneng BM, Dhar N, Nunes MC, Krammer F, Madhi SA, Moore PL, Richardson SI. Hemagglutinin Stalk-Specific Fc-Mediated Functions Are Associated With Protection Against Influenza Illness After Seasonal Influenza Vaccination. J Infect Dis. 2024 Dec 16;230(6):1329-1336. doi: 10.1093/infdis/jiae241.

  PMID: 38743692 DERIVED

• Amin AB, Nunes MC, Tapia MD, Madhi SA, Cutland CL, Wairagkar N, Omer SB; for BMGF Supported Maternal Influenza Immunization Trials Investigators Group. Immunogenicity of influenza vaccines administered to pregnant women in randomized clinical trials in Mali and South Africa. Vaccine. 2020 Sep 22;38(41):6478-6483. doi: 10.1016/j.vaccine.2020.07.020. Epub 2020 Aug 29.

  PMID: 32868130 DERIVED

• Madhi SA, Cutland CL, Downs S, Jones S, van Niekerk N, Simoes EAF, Nunes MC. Burden of Respiratory Syncytial Virus Infection in South African Human Immunodeficiency Virus (HIV)-Infected and HIV-Uninfected Pregnant and Postpartum Women: A Longitudinal Cohort Study. Clin Infect Dis. 2018 May 17;66(11):1658-1665. doi: 10.1093/cid/cix1088.

  PMID: 29253090 DERIVED

• Nunes MC, Cutland CL, Jones S, Downs S, Weinberg A, Ortiz JR, Neuzil KM, Simoes EAF, Klugman KP, Madhi SA. Efficacy of Maternal Influenza Vaccination Against All-Cause Lower Respiratory Tract Infection Hospitalizations in Young Infants: Results From a Randomized Controlled Trial. Clin Infect Dis. 2017 Oct 1;65(7):1066-1071. doi: 10.1093/cid/cix497.

  PMID: 28575286 DERIVED

• Madhi SA, Nunes MC, Weinberg A, Kuwanda L, Hugo A, Jones S, van Niekerk N, Ortiz JR, Neuzil KM, Klugman KP, Simoes EAF, Cutland CL; Maternal Flu Trial (Matflu) Team. Contribution of Serologic Assays in the Evaluation of Influenza Virus Infection Rates and Vaccine Efficacy in Pregnant Women: Report From Randomized Controlled Trials. Clin Infect Dis. 2017 Jun 15;64(12):1773-1779. doi: 10.1093/cid/cix241.

  PMID: 28369198 DERIVED

• Nunes MC, Cutland CL, Jones S, Hugo A, Madimabe R, Simoes EA, Weinberg A, Madhi SA; Maternal Flu Trial Team. Duration of Infant Protection Against Influenza Illness Conferred by Maternal Immunization: Secondary Analysis of a Randomized Clinical Trial. JAMA Pediatr. 2016 Sep 1;170(9):840-7. doi: 10.1001/jamapediatrics.2016.0921.

  PMID: 27380464 DERIVED

• Madhi SA, Cutland CL, Kuwanda L, Weinberg A, Hugo A, Jones S, Adrian PV, van Niekerk N, Treurnicht F, Ortiz JR, Venter M, Violari A, Neuzil KM, Simoes EA, Klugman KP, Nunes MC; Maternal Flu Trial (Matflu) Team. Influenza vaccination of pregnant women and protection of their infants. N Engl J Med. 2014 Sep 4;371(10):918-31. doi: 10.1056/NEJMoa1401480.

  PMID: 25184864 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

• Keith P Klugman, MD, PhD

  Emory University

  STUDY DIRECTOR

• Adriana Weinberg

  University of Denver

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: March 1, 2011
• First Posted: March 2, 2011
• Study Start: March 3, 2011
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: August 6, 2018

Record last verified: 2018-08

Locations

ZA (1)