Safety and Immunogenicity of Measles Vaccine, Varicella Vaccine and Hepatitis-A Vaccine (MV/VV/Hep-AV)

March 15, 2020 updated by: Shabir Madhi, University of Witwatersrand, South Africa

Safety and Immunogenicity of Measles Vaccine, Varicella Vaccine and Hepatitis-A Vaccine in HIV-exposed and HIV-unexposed South African Children

This trial will evaluate the safety and immunogenicity of: i) measles vaccine (CAM-70) after primary dose at 6 months (MV1) and booster vaccination at 12 months (MV2); ii) a single dose of varicella vaccination at 18 months; and iii) a single dose of hepatitis-A vaccination at 18 months in HIV-exposed and HIV-unexposed South African children.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Measles vaccine (MV) can reduce childhood mortality and is currently recommended to all South African children aged 6 months. Only one study has examined the safety and immunogenicity of the recommended CAM-70 measles vaccine strain in children under 9 months of age. In addition, there are limited data on the safety and immunogenicity of varicella vaccine (VV) and Hepatitis-A vaccination (Hep-AV) in HIV-exposed and HIV-unexposed children in Sub-Saharan Africa.

This is a prospective, observational cohort study nested within a larger randomized, open-label trial on pneumococcal-conjugate vaccine (PCV) titled PCV1+1. 70 HIV-exposed and 200 HIV-unexposed children will be enrolled at Chris Hani Baragwanath Academic Hospital (CHBAH) and neighbouring primary health clinics.

Immune responses to the vaccines will be measured as rate of seroconversion, rate of seroprotection, and geometric mean titres (GMT) one month post primary immunization (MV1, VV, Hep-AV) and one month post booster dose (MV2). In addition, pre-vaccination and medium long-term antibody levels at 4.5 months, 12 months and 18 months will be evaluated. Number of adverse events in all immunized infants will be recorded throughout the study duration and compared between groups. Long-term antibody levels at 3, 4 and 5 years of age will be measured during annual follow-up visits.

This study will add to the current evidence on immunizing infants with MV (CAM-70) at 6 and 12 months of age. Data will be stratified by HIV-exposure and HIV-infection, thereby offering insight in the influence of HIV on post-vaccination immune responses. The findings on VV/Hep-AV safety, immunogenicity and seroprevalence will be useful to informing future immunization policies in Sub-Saharan Africa.

Study Type

Interventional

Enrollment (Actual)

278

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • South Africa
    • Gauteng
      • Soweto, Gauteng, South Africa, 2013
        • Chris Hani Baragwanath Academic Hospital; Nrf/Dst Vpd Rmpru

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

4 months to 1 year (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Aged ≤18 weeks;
  2. Parent/guardian able to provide informed consent;
  3. Available for the duration of the study;
  4. Enrolled as a participant in the PVC1+1 trial AND born to HIV-uninfected woman; OR Born to HIV-infected mother AND infant CD4% ≥25% if HIV-infected;
  5. Birth weight >2499g AND weight of >3.5 kg at time of proposed enrolment;
  6. Being a healthy child (except for HIV status in HIV-exposed cohort) based on medical history and physical examination by the study staff.

Exclusion Criteria:

  1. Significant major congenital abnormalities;
  2. Received measles vaccination, varicella vaccination or hepatitis-A vaccination since birth;
  3. Previous hospitalization for respiratory illness following discharge from hospital at birth;
  4. Known allergy to vaccine components;
  5. Febrile illness (axillary temperature ≥37.8°C) at time of screening;
  6. Known or suspected immunodeficiency condition other than HIV;
  7. Planning to relocate outside of the study area during the study period;
  8. Receipt of blood transfusion or any other blood products (including immunoglobulins) since birth, receipt of such products during the course of the study will require withdrawal of the child from the study;
  9. History of confirmed measles, varicella or hepatitis-A disease since birth.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: HIV-unexposed children
HIV-unexposed children enrolled in a randomized open label study on the pneumococcal conjugate vaccine (PCV1+1) will be invited to participate in this study. Children enrolled in the PCV1+1 study will receive all vaccines included in the South African public immunization program. Measles vaccine (0.5 mL, subcutaneous injection) will be adminstered at 6 months of age and 12 months of age. Varicella vaccine (0.5 mL, subcutaneous injection) or Hepatitis-A vaccine (0.5 mL, intra-muscular injection) will be administered to the participants at 18 months of age as an additional benefit for participating in the study.
Biological: Measles vaccine
All participants will receive measles vaccine at 6 and 12 months of age, according to the South African immunization schedule. All study vaccines are currently licensed in South Africa and will be administered according to their approved dosages, formulations and indications.
Other Names:
  • Measles vaccine (MeasBio) 0.5 mL
Biological: Hepatitis-A vaccine
Half of the participants (n=135) will receive hepatitis-A vaccine at 18 months of age.
Other Names:
  • Hepatitis-A vaccine (Varilrix) 0.5 mL
Biological: Varicella vaccine
Half of the participants (n=135) will receive varicella vaccine at 18 months of age.
Other Names:
  • Varicella vaccine (Avaxim Paediatric) 0.5 mL
Other: HIV-exposed children
A cohort of HIV-exposed children will be recruited. Measles vaccine (0.5 mL, subcutaneous injection) will be adminstered at 6 months of age and 12 months of age. Varicella vaccine (0.5 mL, subcutaneous injection) or Hepatitis-A vaccine (0.5 mL, intra-muscular injection) will be administered to the participants at 18 months of age as an additional benefit for participating in the study.
Biological: Measles vaccine
All participants will receive measles vaccine at 6 and 12 months of age, according to the South African immunization schedule. All study vaccines are currently licensed in South Africa and will be administered according to their approved dosages, formulations and indications.
Other Names:
  • Measles vaccine (MeasBio) 0.5 mL
Biological: Hepatitis-A vaccine
Half of the participants (n=135) will receive hepatitis-A vaccine at 18 months of age.
Other Names:
  • Hepatitis-A vaccine (Varilrix) 0.5 mL
Biological: Varicella vaccine
Half of the participants (n=135) will receive varicella vaccine at 18 months of age.
Other Names:
  • Varicella vaccine (Avaxim Paediatric) 0.5 mL

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with seroprotective antibody titres (IgG ≥330 mIU/ml quantified by ELISA) one month post booster measles vaccination
Time Frame: 13 months of age (one month post booster measles vaccine)
Measured as seroprotection rate one month post booster measles vaccine in HIV-exposed (HEU, HIV-infected) and HIV-unexposed South African children.
13 months of age (one month post booster measles vaccine)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with seroprotective antibody titres (IgG ≥300 mIU/ml quantified by ELISA) one month post varicella vaccination
Time Frame: 19 months of age (one month post vaccination)
Measured as seroprotection rate one month post varicella immunization in HIV-exposed (HEU, HIV-infected) and HIV-unexposed South African children.
19 months of age (one month post vaccination)
Number of participants with seroprotective antibody titres (IgG ≥20 mIU/ml quantified by ELISA) one month post hepatitis-A vaccination
Time Frame: 19 months of age (one month post vaccination)
Measured as seroprotection rate one month post hepatitis-A immunization in HIV-exposed (HEU, HIV-infected) and HIV-unexposed South African children.
19 months of age (one month post vaccination)
Number of participants with vaccine-related adverse events after primary measles vaccination
Time Frame: 6 months of age
Participants will be observed for at least 30 minutes after vaccination so that clinic personnel can observe and document any potential adverse reactions to the vaccine. Report of vaccine-related local (redness, swelling, pain/tenderness, itching) and systemic (fever, vomiting, poor appetite, irritability and decreased activity) adverse events will be solicited using diary card in the 7 days after vaccination.
6 months of age
Number of participants with vaccine-related adverse events after booster measles vaccination
Time Frame: 12 months of age
Participants will be observed for at least 30 minutes after vaccination so that clinic personnel can observe and document any potential adverse reactions to the vaccine. Report of vaccine-related local (redness, swelling, pain/tenderness, itching) and systemic (fever, vomiting, poor appetite, irritability and decreased activity) adverse events will be solicited using diary card in the 7 days after vaccination.
12 months of age
Number of participants with vaccine-related adverse events after varicella vaccination
Time Frame: 18 months of age
Participants will be observed for at least 30 minutes after vaccination so that clinic personnel can observe and document any potential adverse reactions to the vaccine. Report of vaccine-related local (redness, swelling, pain/tenderness, itching) and systemic (fever, vomiting, poor appetite, irritability and decreased activity) adverse events will be solicited using diary card in the 7 days after vaccination.
18 months of age
Number of participants with vaccine-related adverse events after hepatitis-A vaccination
Time Frame: 18 months of age
Participants will be observed for at least 30 minutes after vaccination so that clinic personnel can observe and document any potential adverse reactions to the vaccine. Report of vaccine-related local (redness, swelling, pain/tenderness, itching) and systemic (fever, vomiting, poor appetite, irritability and decreased activity) adverse events will be solicited using diary card in the 7 days after vaccination.
18 months of age
Persistence of immunogenicity
Time Frame: 3, 4 and 5 years of age
Antibody concentrations and number of participants with seroprotective antibody levels to measles, varicella and hepatitis-A vaccination
3, 4 and 5 years of age

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Witwatersrand, South Africa

Investigators

  • Principal Investigator: Shabir A Madhi, MD, PhD, University of Witwatersrand, South Africa

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 10, 2017

Primary Completion (Actual)

February 26, 2019

Study Completion (Anticipated)

December 1, 2022

Study Registration Dates

First Submitted

October 12, 2017

First Submitted That Met QC Criteria

October 30, 2017

First Posted (Actual)

November 6, 2017

Study Record Updates

Last Update Posted (Actual)

March 17, 2020

Last Update Submitted That Met QC Criteria

March 15, 2020

Last Verified

March 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MV/VV/Hep-AV

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

Currently no plan to share IPD.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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