Clinical trial NCT03330171: Safety and Immunogenicity of Measles Vaccine, Varicella Vaccine and Hepatitis-A Vaccine
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
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Measles
Varicella
Hepatitis A
Keywords: Immunogenicity
Safety
Vaccine
Lead sponsor: University of Witwatersrand, South Africa
Sponsor class: OTHER
First posted: 2017-11-06
Enrollment: 278
Sex: ALL
Minimum age (years): 18
Maximum age (years): 19
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention 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.
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of participants with seroprotective antibody titres (IgG ≥330 mIU/ml quantified by ELISA) one month post booster measles vaccination
timeFrame: 13 months of age (one month post booster measles vaccine)
Secondary outcomes:
measure: Number of participants with seroprotective antibody titres (IgG ≥300 mIU/ml quantified by ELISA) one month post varicella vaccination
timeFrame: 19 months of age (one month post vaccination)
measure: Number of participants with seroprotective antibody titres (IgG ≥20 mIU/ml quantified by ELISA) one month post hepatitis-A vaccination
timeFrame: 19 months of age (one month post vaccination)
measure: Number of participants with vaccine-related adverse events after primary measles vaccination
timeFrame: 6 months of age
measure: Number of participants with vaccine-related adverse events after booster measles vaccination
timeFrame: 12 months of age
measure: Number of participants with vaccine-related adverse events after varicella vaccination
timeFrame: 18 months of age
measure: Number of participants with vaccine-related adverse events after hepatitis-A vaccination
timeFrame: 18 months of age
measure: Persistence of immunogenicity
timeFrame: 3, 4 and 5 years of age
Other outcomes:
Locations:
city: Soweto
country: South Africa
facility: Chris Hani Baragwanath Academic Hospital; Nrf/Dst Vpd Rmpru
state: Gauteng
Study officials:
affiliation: University of Witwatersrand, South Africa
name: Shabir A Madhi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.