Clinical Efficacy of Typhoid Conjugate Vaccine (Vi-TCV) Among Children Age 9 Months Through 12 Years in Blantyre, Malawi
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03299426|
Recruitment Status : Active, not recruiting
First Posted : October 3, 2017
Last Update Posted : February 16, 2022
|Condition or disease||Intervention/treatment||Phase|
|Typhoid||Biological: Vi-Typhoid Conjugate Vaccine (Vi-TCV) Biological: Meningococcal A Conjugate Vaccine (MCV-A)||Phase 3|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30000 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Investigator, Outcomes Assessor)|
|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|
|Actual Study Start Date :||February 21, 2018|
|Estimated Primary Completion Date :||October 30, 2022|
|Estimated Study Completion Date :||October 30, 2022|
Experimental: Vi-Typhoid Conjugate Vaccine (Vi-TCV)
Children will receive a single 0.5-ml dose of Vi-TCV administered by the intramuscular route.
Biological: Vi-Typhoid Conjugate Vaccine (Vi-TCV)
Single 0.5-ml intramuscular injection
Active Comparator: Meningococcal A Conjugate Vaccine (MCV-A)
Children will receive a single dose of MCV-A administered by the intramuscular route. Children 9-11 months will receive a 5µg/0.5ml dose. Children 12 months and older will receive a 10µg/0.5 ml dose.
Biological: Meningococcal A Conjugate Vaccine (MCV-A)
Single intramuscular injection. Children 9-11 months will receive a 5µg/0.5ml dose. Children 12 months and older will receive a 10µg/0.5 ml dose.
- Efficacy of Vi-TCV [ Time Frame: Up to 36 months ]The primary outcome of interest is the incidence of blood culture-positive typhoid fever among Vi-TCV and MCV-A vaccine recipients in the study population during the entire post-vaccination surveillance period. Vaccine efficacy will be calculated as one minus the relative rate of symptomatic typhoid fever in the Vi-TCV group compared to that in the MCV-A group.
- Safety of Vi-TCV [ Time Frame: 6 months ]
The safety profile of Vi-TCV will be measured by comparing the proportions of participants experiencing solicited and unsolicited local and systemic reactions between children receiving Vi-TCV as compared to children receiving MCV-A according to the following three categories:
- The proportion of participants who develop adverse events detected in the first 30 minutes after vaccination and for 7 days after vaccination.
- The proportion of participants who experience serious adverse events within 6 months of vaccination in a subset of participants.
- The proportion of participants who experience other non-serious adverse events up to 28 days following vaccination, in a subset of participants.
- Immunogenicity of Vi-TCV [ Time Frame: 28 days ]The immunogenicity of Vi-TCV in a subset of 600 participants measured by ELISA for anti-Vi percent seroconversion and GMTs before and at day 28 after vaccination.
- Number of typhoid fever cases prevented Vi-TCV [ Time Frame: Up to 36 months ]The number of blood culture-confirmed cases of typhoid fever prevented by Vi-TCV during the study period measured by comparing the incidence of blood culture-confirmed typhoid fever in participants receiving Vi-TCV compared to those receiving MCV-A.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03299426
|Malawi Liverpool Wellcome Trust Clinical Research Programme, Queen Elizabeth Central Hospital College of Medicine|
|Blantyre, Malawi, P.O. Box 30096|
|Principal Investigator:||Kathleen Neuzil, MD||University of Maryland School of Medicine|