Clinical Efficacy of Typhoid Conjugate Vaccine (Vi-TCV) Among Children Age 9 Months Through 12 Years in Blantyre, Malawi

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Brief Title

Clinical Efficacy of Typhoid Conjugate Vaccine (Vi-TCV) Among Children Age 9 Months Through 12 Years in Blantyre, Malawi

Official Title

A Phase III Randomized, Double-Blind, Controlled Trial of the Clinical Efficacy of Typhoid Conjugate Vaccine (Vi-TCV) Among Children Age 9 Months Through 12 Years in Blantyre, Malawi

Brief Summary

      This study will evaluate the efficacy of a Typhoid conjugate vaccine (Vi-TCV) in Malawi,
      Africa among children age 9 months through 12 years. Participants will be randomized in a 1:1
      ration to receive the study vaccine or the control vaccine (meningococcal group A conjugate
      vaccine - MCV-A).
    

Detailed Description

      This study is a double-blind, individually randomized, controlled, clinical efficacy trial
      with two vaccine groups: Vi-TCV (Typhoid conjugate) and MCV-A (meningococcal group A
      conjugate). This study will take place in Blantyre, Malawi, Africa. Participants (up to
      30,000) will be randomized in a 1:1 ratio. Children 9 months through 12 years of age in the
      Blantyre area who meet the inclusion criteria will be eligible for enrollment.

      Participants will be unaware of which study vaccine, Vi-TCV or MCV-A, is received. A subset
      of 600 children will have study visits on days 3, 7, 28 and 180 post-vaccination to assess
      select solicited events, unsolicited events, and all serious adverse events. Serious Adverse
      Events (SAEs) in all participants will be monitored through the end of the trial.

      For the evaluation of efficacy, passive surveillance will be conducted for up to 36 months to
      identify cases among vaccinated subjects. Children who meet the protocol-defined specimen
      collection criteria will have a blood culture collected. Additional information will be
      collected from any child who has a blood culture obtained. This will include information
      about the signs and symptoms of the illness and treatment given. Likewise, any child with
      blood culture-confirmed typhoid fever will have follow-up until the illness resolves.
      Additional information on the illness, treatment and complications will be recorded. Vaccine
      efficacy will be evaluated when the pre-specified number of cases is reached after a minimum
      of two years of follow-up on each participant.

      A subset of 600 children (200 in each of three age groups: 9-11 months, 1-5 years, and 6-12
      years) will be included in an additional Vaccine Immunogenicity and Reactogenicity Sub-study.
      More stringent exclusion criteria will apply for this subset. The purpose of this detailed
      evaluation is to assess the reactogenicity of the vaccine and the immune responses to Vi-TCV.
      Serum specimens will be collected on day 0 (before vaccination) and on post-vaccination days
      28 and 730 from all children included in the sub-study. For the children in the 9-11 month
      group, Vi-TCV or MCV-A will be administered with measles-containing vaccine, as per Malawi
      Expanded Programme on Immunization (EPI) schedule. These 9-11-month-old children will have
      antibody to measles assessed on days 0 and 28. All children in the sub-study will have visits
      at days 4 and 7 following vaccination for solicitation of local and systemic adverse events.
      Serious and non-serious adverse events will be assessed at days 28 and 180.

      An additional subset of -up to 225 HIV-exposed-but-uninfected and up to 100 HIV-unexposed
      children ages 9-11 months will be included in an additional HIV-exposed Vaccine
      Immunogenicity and Reactogenicity Substudy. The purpose of this detailed evaluation is to
      assess the reactogenicity of the vaccine and the immune responses to one or two doses of
      Vi-TCV in HIV-exposed children. Up to 225 HIV-exposed children in this substudy will be
      randomized 1:1:1 to receive either TCV at 9-11 months and TCV at 15 months (Group 1), TCV at
      9-11 months only (Group 2), or TCV at 15 months only (Group 3). A separate group of about 100
      HIV-unexposed children will serve as controls and receive TCV at 9-11 months and TCV at 15
      months (Group 4). Serum specimens will be collected on day 0 (before vaccination) and on 28
      days after each vaccination from all children included in the sub-study. For this substudy,
      Vi-TCV will be administered with measles-rubella-containing vaccine #1 at 9-11 months and/or
      #2 at 15 months, as per Malawi EPI schedule. These 9-11-month-old children will have antibody
      to typhoid, measles, and rubella assessed on day 0 and 28 days after each vaccination. All
      children in the sub-study will be assessed at 7 days after each vaccination for solicitation
      of local and systemic adverse events. Serious and non-serious adverse events will be assessed
      up to the last study visit for HIV-exposed substudy participants.
    

Study Phase

Phase 3

Study Type

Interventional


Primary Outcome

Efficacy of Vi-TCV

Secondary Outcome

 Safety of Vi-TCV

Condition

Typhoid

Intervention

Vi-Typhoid Conjugate Vaccine (Vi-TCV)

Study Arms / Comparison Groups

 Vi-Typhoid Conjugate Vaccine (Vi-TCV)
Description:  Children will receive a single 0.5-ml dose of Vi-TCV administered by the intramuscular route.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

30000

Start Date

February 21, 2018

Completion Date

September 30, 2021

Primary Completion Date

September 30, 2021

Eligibility Criteria

        Inclusion Criteria:

          -  Healthy male or female child between the ages of 9 months and 12 years/364 days at the
             time of study vaccination.

          -  A child whose parent or guardian resides primarily within the Ndirande or Zingwangwa
             study areas at the time of study vaccinations and who intends to be present in the
             area for the duration of the trial.

          -  A child whose parent or guardian has voluntarily given informed consent.

        Exclusion Criteria:

          -  History of documented hypersensitivity to any component of the vaccine

          -  Prior receipt of any typhoid vaccine in the past 3 years

          -  History of severe allergic reaction with generalized urticarial, angioedema, or
             anaphylaxis

          -  Any condition determined by the investigator to be likely to interfere with evaluation
             of the vaccine or to be a significant potential health risk to the child or make it
             unlikely that the child would complete the study.

        Temporary Exclusion Criteria:

        The following will be considered temporary contraindications to enrollment and vaccination.
        If these apply, the participant will be temporarily excluded for vaccination until 48 hours
        has passed. A re-assessment will be needed to ensure these temporary exclusion criteria no
        longer exist.

          -  Reported fever within 24 hours prior to vaccination

          -  Use of anti-pyretics within 4 hours prior to vaccination

        An additional temporary exclusion criteria will be:

        - Receipt of measles vaccine in the one month prior to enrollment, as determined by
        parental history or vaccination card.

        Additional Exclusion Criteria for Safety and Immunogenicity Substudy:

        In addition to the exclusion criteria of the efficacy study, participants enrolled in the
        immunogenicity and reactogenicity substudy may not have, or have had, any:

          -  Known history of diabetes, tuberculosis, cancer, chronic kidney, heart, or liver
             disease, progressive neurological disorders, poorly controlled seizures, or terminal
             illness

          -  Severe malnutrition as determined by MUAC< 12.5 cm for children younger than 5 years;

          -  Receipt of any other investigational intervention in the last 6 months or anticipated
             during the course of the study.

          -  Receipt of blood products in the last 6 months.

          -  Known HIV-infection or exposure or other immunosuppressive conditions.

          -  Receipt of systemic immunosuppressant or systemic corticosteroids.

          -  Receipt of any measles-containing vaccine for children younger than 1 year of age
      

Gender

All

Ages

9 Months - 12 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Kathleen Neuzil, MD, 410-706-8061, [email protected]

Location Countries

Malawi

Location Countries

Malawi

Administrative Informations


NCT ID

NCT03299426

Organization ID

HP-00076625


Responsible Party

Principal Investigator

Study Sponsor

University of Maryland, Baltimore

Collaborators

 Bill and Melinda Gates Foundation

Study Sponsor

Kathleen Neuzil, MD, Principal Investigator, University of Maryland, College Park


Verification Date

April 2021