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

Primary Purpose

Measles, Varicella, Hepatitis A

Status
Unknown status
Phase
Phase 4
Locations
South Africa
Study Type
Interventional
Intervention
Measles vaccine
Hepatitis-A vaccine
Varicella vaccine
Sponsored by
University of Witwatersrand, South Africa
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Measles focused on measuring Immunogenicity, Safety, Vaccine

Eligibility Criteria

18 Weeks - 19 Months (Child)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Chris Hani Baragwanath Academic Hospital; Nrf/Dst Vpd Rmpru

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

HIV-unexposed children

HIV-exposed children

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Number of participants with seroprotective antibody titres (IgG ≥300 mIU/ml quantified by ELISA) one month post varicella vaccination
Measured as seroprotection rate one month post varicella immunization in HIV-exposed (HEU, HIV-infected) and HIV-unexposed South African children.
Number of participants with seroprotective antibody titres (IgG ≥20 mIU/ml quantified by ELISA) one month post hepatitis-A vaccination
Measured as seroprotection rate one month post hepatitis-A immunization in HIV-exposed (HEU, HIV-infected) and HIV-unexposed South African children.
Number of participants with vaccine-related adverse events after primary measles vaccination
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.
Number of participants with vaccine-related adverse events after booster measles vaccination
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.
Number of participants with vaccine-related adverse events after varicella vaccination
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.
Number of participants with vaccine-related adverse events after hepatitis-A vaccination
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.
Persistence of immunogenicity
Antibody concentrations and number of participants with seroprotective antibody levels to measles, varicella and hepatitis-A vaccination

Full Information

First Posted
October 12, 2017
Last Updated
March 15, 2020
Sponsor
University of Witwatersrand, South Africa
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1. Study Identification

Unique Protocol Identification Number
NCT03330171
Brief Title
Safety and Immunogenicity of Measles Vaccine, Varicella Vaccine and Hepatitis-A Vaccine
Acronym
MV/VV/Hep-AV
Official Title
Safety and Immunogenicity of Measles Vaccine, Varicella Vaccine and Hepatitis-A Vaccine in HIV-exposed and HIV-unexposed South African Children
Study Type
Interventional

2. Study Status

Record Verification Date
March 2020
Overall Recruitment Status
Unknown status
Study Start Date
April 10, 2017 (Actual)
Primary Completion Date
February 26, 2019 (Actual)
Study Completion Date
December 1, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Witwatersrand, South Africa

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Measles, Varicella, Hepatitis A
Keywords
Immunogenicity, Safety, Vaccine

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Model Description
Participants receive measles vaccine as part of routine medical care at 6 and 12 months of age. Half of the participants will receive varicella vaccine at 18 months of age and the other half will receive hepatitis-A at 18 months of age. All vaccines are administered according to their approved dosages, formulations and indications.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
278 (Actual)

8. Arms, Groups, and Interventions

Arm Title
HIV-unexposed children
Arm Type
Other
Arm Description
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.
Arm Title
HIV-exposed children
Arm Type
Other
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Measles vaccine
Other Intervention Name(s)
Measles vaccine (MeasBio) 0.5 mL
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
Hepatitis-A vaccine
Other Intervention Name(s)
Hepatitis-A vaccine (Varilrix) 0.5 mL
Intervention Description
Half of the participants (n=135) will receive hepatitis-A vaccine at 18 months of age.
Intervention Type
Biological
Intervention Name(s)
Varicella vaccine
Other Intervention Name(s)
Varicella vaccine (Avaxim Paediatric) 0.5 mL
Intervention Description
Half of the participants (n=135) will receive varicella vaccine at 18 months of age.
Primary Outcome Measure Information:
Title
Number of participants with seroprotective antibody titres (IgG ≥330 mIU/ml quantified by ELISA) one month post booster measles vaccination
Description
Measured as seroprotection rate one month post booster measles vaccine in HIV-exposed (HEU, HIV-infected) and HIV-unexposed South African children.
Time Frame
13 months of age (one month post booster measles vaccine)
Secondary Outcome Measure Information:
Title
Number of participants with seroprotective antibody titres (IgG ≥300 mIU/ml quantified by ELISA) one month post varicella vaccination
Description
Measured as seroprotection rate one month post varicella immunization in HIV-exposed (HEU, HIV-infected) and HIV-unexposed South African children.
Time Frame
19 months of age (one month post vaccination)
Title
Number of participants with seroprotective antibody titres (IgG ≥20 mIU/ml quantified by ELISA) one month post hepatitis-A vaccination
Description
Measured as seroprotection rate one month post hepatitis-A immunization in HIV-exposed (HEU, HIV-infected) and HIV-unexposed South African children.
Time Frame
19 months of age (one month post vaccination)
Title
Number of participants with vaccine-related adverse events after primary measles vaccination
Description
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.
Time Frame
6 months of age
Title
Number of participants with vaccine-related adverse events after booster measles vaccination
Description
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.
Time Frame
12 months of age
Title
Number of participants with vaccine-related adverse events after varicella vaccination
Description
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.
Time Frame
18 months of age
Title
Number of participants with vaccine-related adverse events after hepatitis-A vaccination
Description
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.
Time Frame
18 months of age
Title
Persistence of immunogenicity
Description
Antibody concentrations and number of participants with seroprotective antibody levels to measles, varicella and hepatitis-A vaccination
Time Frame
3, 4 and 5 years of age

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Weeks
Maximum Age & Unit of Time
19 Months
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Aged ≤18 weeks; Parent/guardian able to provide informed consent; Available for the duration of the study; 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; Birth weight >2499g AND weight of >3.5 kg at time of proposed enrolment; 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: Significant major congenital abnormalities; Received measles vaccination, varicella vaccination or hepatitis-A vaccination since birth; Previous hospitalization for respiratory illness following discharge from hospital at birth; Known allergy to vaccine components; Febrile illness (axillary temperature ≥37.8°C) at time of screening; Known or suspected immunodeficiency condition other than HIV; Planning to relocate outside of the study area during the study period; 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; History of confirmed measles, varicella or hepatitis-A disease since birth.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shabir A Madhi, MD, PhD
Organizational Affiliation
University of Witwatersrand, South Africa
Official's Role
Principal Investigator
Facility Information:
Facility Name
Chris Hani Baragwanath Academic Hospital; Nrf/Dst Vpd Rmpru
City
Soweto
State/Province
Gauteng
ZIP/Postal Code
2013
Country
South Africa

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Currently no plan to share IPD.
Citations:
PubMed Identifier
32307279
Citation
Mutsaerts EAML, Nunes MC, Bhikha S, Ikulinda BT, Jose L, Koen A, Moultrie A, Grobbee DE, Klipstein-Grobusch K, Weinberg A, Madhi SA. Short-term immunogenicity and safety of hepatitis-A and varicella vaccines in HIV-exposed uninfected and HIV-unexposed South African children. Vaccine. 2020 May 8;38(22):3862-3868. doi: 10.1016/j.vaccine.2020.03.045. Epub 2020 Apr 16.
Results Reference
derived
PubMed Identifier
31282539
Citation
Mutsaerts EAML, Nunes MC, Bhikha S, Ikulinda BT, Boyce W, Jose L, Koen A, Moultrie A, Cutland CL, Grobbee DE, Klipstein-Grobusch K, Madhi SA. Immunogenicity and Safety of an Early Measles Vaccination Schedule at 6 and 12 Months of Age in Human Immunodeficiency Virus (HIV)-Unexposed and HIV-Exposed, Uninfected South African Children. J Infect Dis. 2019 Sep 26;220(9):1529-1538. doi: 10.1093/infdis/jiz348.
Results Reference
derived

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Safety and Immunogenicity of Measles Vaccine, Varicella Vaccine and Hepatitis-A Vaccine

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