Safety and Immunogenicity Study of Influenza Vaccines in HIV-infected and HIV-uninfected Pregnant Women in Western Kenya

NCT01810731 | Withdrawn Phase 2 DMC

• 1 other identifier: CDC-NCIRD-6393
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

In 2012, the WHO Strategic Advisory Group of Experts (SAGE) concluded that pregnant women are the most important risk group for season influenza vaccination based upon "compelling evidence of substantial risk of severe disease in this group and evidence that seasonal influenza vaccine is safe and effective in preventing disease in pregnant women as well as their young infants, in whom disease burden is also high". Recent data from Kenya, similarly suggest rates of influenza-associated hospitalizations in children under age 1 to be as high, or higher, than those observed in the United States. However, TIV may have reduced immunogenicity in HIV-infected adults, and HIV infection has been shown to reduce placental transfer of both tetanus and measles antibodies. Therefore, we propose to conduct a double-blind randomized controlled trial of influenza vaccines stratified by HIV status in up to 720 pregnant women in their second and third trimesters and their infants residing in health and demographic surveillance sites (HDSS) in Nyanza Province, Western Kenya. We propose to assess the safety, immunogenicity, and efficacy of standard dose QIV and double dose QIV in HIV-infected and HIV-uninfected pregnant women. Findings will inform maternal influenza vaccination policies in Kenya and other African countries.

Conditions

Influenza, Human; HIV; Malaria; Tetanus; Polio

Keywords

influenza vaccine immunogenicity; HIV; pregnancy; influenza vaccine safety

Outcome Measures

Primary Outcomes (3)

• Proportion of women with an appropriate rise in Hemagglutination Inhibition (HI) titers

  The proportion of standard dose (15 µg) QIV and double dose (30 µg) QIV recipients with a fourfold rise in HI titers or HI titers ≥40 if baseline HI titer \<10 compared to the same proportion in controls

  Enrollment (Day 0) vs. Day 28 for each study arm

• Proportion of infants born to standard dose (15 µg) QIV and double dose (30 µg) QIV recipients with HI titers greater than or equal to 40 in cord blood compared to same in controls.

  At delivery

• Number of solicited and unsolicited adverse events post-vaccination by study arm

  During follow-up period, approx. 9 months

Secondary Outcomes (5)

• Vaccine efficacy of standard dose (15 µg) QIV and double dose (30 µg) QIV in mothers and infants compared to control mothers and infants.

  Entire follow-up period, approx. 9 months

• HIV infection and placental antibody transfer

  Delivery

• Birth weight

  Delivery

• Peripheral and placental parasitemia impact on vaccination

  Day 0 and delivery

• baseline polio immunity and polio antibody transfer

  day 0 and delivery

Study Arms (3)

Quadrivalent Influenza Vaccine (QIV)

EXPERIMENTAL

15µg of each of 2 influenza A strains (H1N1 and H3N2) and 2 influenza B strains in a buffer solution totaling 0.5mL which is administered intramuscularly. Administered as a single dose on the day of enrollment.

Biological: Quadrivalent Inactivated Influenza Vaccine (QIV)

Inactivated Polio Vaccine

ACTIVE COMPARATOR

A sterile suspension of three types of poliovirus: Type 1 (Mahoney), Type 2 (MEF1) and Type 3 (Saukett). This vaccine is prepared from types 1, 2 and 3 of poliomyelitis virus cultured on Vero cells, purified and then inactivated by formaldehyde and administered as a 0.5ml intramuscular or subcutaneous injection. A single dose of vaccine will be administered upon enrollment.

Biological: Inactivated Polio Vaccine

Double Dose QIV

EXPERIMENTAL

30µg of each of 2 influenza A strains (H1N1 and H3N2) and 2 influenza B strains in a buffer solution totaling 1.0mL which is administered intramuscularly. Administered as a single dose on the day of enrollment.

Biological: Double Dose QIV

Interventions

Quadrivalent Inactivated Influenza Vaccine (QIV) BIOLOGICAL

Also known as: Fluarix, (GlaxoSmithKline Biologicals, Dresden, Germany)

Quadrivalent Influenza Vaccine (QIV)

Inactivated Polio Vaccine BIOLOGICAL

Also known as: Imovax, Sanofi Pasteur SA

Inactivated Polio Vaccine

Double Dose QIV BIOLOGICAL

Also known as: Fluarix (GlaxoSmithKline Biologicals, Dresden, Germany)

Double Dose QIV

Eligibility Criteria

• Age: 13 Years - 49 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Resident of HDSS village
• Singleton pregnancy
• Second or third trimester (after quickening) but before 33 weeks of gestation by fundal height
• Does not plan to relocate out of the HDSS area or population-based surveillance site in the next 12 months and agrees to all follow-up visits/contact by phone
• Is not currently enrolled in another intervention study
• Provides informed consent by signature or thumb print
• Consents to HIV testing and counseling as required
• Willing to deliver in the labor ward of the study hospital
• No history of chronic illness requiring multiple hospitalizations or prolonged medical therapy (except HIV on ART)

You may not qualify if:

• History of allergic reaction to any component of the study vaccines
• Residence outside the study area or planning to relocate out in the 9 months following enrollment
• Received immunoglobulin or blood products within 45 days of study entry
• Used immunosuppressive medication within 45 days of study entry (inhaled and topical corticosteroids permitted)
• High risk pregnancy including any pre-existing condition likely to cause complications of pregnancy (hypertension, diabetes, current asthma, eclampsia or pre-eclampsia, epilepsy, heart disease, renal disease, liver disease, fistula repair, leg or spine deformity)
• Unable to give informed consent (for example due to mental disability)
• Previous enrollment in a study with similar interventions
• Gestational age \>32 weeks by last menstrual period or fundal height
• Acutely ill with temperature ≥37.5°C on the day of randomization/vaccination
• Hemoglobin \<7.0 g/dL
• Influenza vaccination in previous 12 months

Sponsors & Collaborators

• Centers for Disease Control and Prevention: lead

Study Sites (1)

Siaya District Hospital

Siaya, Kenya

Location

MeSH Terms

Conditions

Influenza, Human; Malaria; Tetanus; Poliomyelitis

Interventions

Influenza Vaccines; fluarix; Poliovirus Vaccine, Inactivated; Rabies Vaccines

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Protozoan Infections; Parasitic Diseases; Mosquito-Borne Diseases; Vector Borne Diseases; Clostridium Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Myelitis; Central Nervous System Infections; Enterovirus Infections; Picornaviridae Infections; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Neuroinflammatory Diseases; Neuromuscular Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures; Vaccines, Inactivated; Poliovirus Vaccines

Study Officials

• Meredith L McMorrow, MD, MPH

  Centers for Disease Control and Prevention

  STUDY DIRECTOR

• Joshua A Mott, PhD

  Centers for Disease Control and Prevention Kenya Country Office

  PRINCIPAL INVESTIGATOR

• Nancy Otieno, MS

  Kenya Medical Research Institute

  PRINCIPAL INVESTIGATOR

• Marc-Alain Widdowson, VetMB, MSc

  Centers for Disease Control and Prevention

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2013
• First Posted: March 13, 2013
• Study Start: April 1, 2014
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: April 10, 2014

Record last verified: 2014-04

Locations

KE (1)