Assessing optimal timing for childhood vaccines in Uganda
| ISRCTN | ISRCTN60356654 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN60356654 |
| Secondary identifying numbers | V1.3 November 2019 |
- Submission date
- 05/02/2021
- Registration date
- 17/02/2021
- Last edited
- 28/06/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English summary of protocol
Background and study aims
Vaccines help protect our bodies against diseases. When a child comes into contact with a disease against which they have been vaccinated, their body will be able to recognise and fight the disease. Without vaccines, children are at increased risk of catching many serious diseases.
The World Health Organization (WHO) recommends that all children receive a number of different vaccines at specific ages. One of the vaccines recommended protects against 5 diseases called diphtheria, tetanus, whooping cough, hepatitis B and Haemophilus influenzae type b (Hib) infection, which can cause pneumonia and meningitis. This vaccine is sometimes called a DTP-containing vaccine. Many countries around the world gives this vaccine at different time points and it is not known which schedule is best. This study aims to determine the best schedule for the DTP-containing vaccine.
Who can participate?
Children aged between 42 and 50 days
What does the study involve?
Participants will be randomly allocated to one of five groups which will each involve different immunisation schedules of the vaccine containing DTP. Participants will have an equal chance of being allocated to each group. The timing of doses, and whether a child receives two or three doses (as both have been shown to be effective), will vary between each group. Children will then have blood tests taken to see whether they have antibodies for DTP before they receive their booster doses.
What are the possible benefits and risks of participating?
The benefits include the opportunity to receive vaccines for Typhoid and Varicella which are not currently included as part of the Expanded Programme on Immunisation. The risks are those associated with phlebotomy (blood-drawing), and include pain and discomfort.
Where is the study run from?
The Masaka Field site, managed by the MRC/UVRI and LSHTM Uganda Research Unit (Uganda)
When is the study starting and how long is it expected to run for?
June 2019 to June 2024
Who is funding the study?
Bill and Melinda Gates Foundation (USA)
Who is the main contact?
1. Professor Andrew Pollard (scientific), andrew.pollard@paediatrics.ox.ac.uk
2. Sarah Kelly (public), sarah.kelly@paediatrics.ox.ac.uk
Contact information
Scientific
Oxford Vaccine Group
Centre for Clinical Vaccinology and Tropical Medicine (CCVTM)
Churchill Hospital
Old Road
Headington
Oxford
OX3 7LE
United Kingdom
 ORCID ID |
0000-0001-7361-719X |
|---|---|
| Phone | +44 (0)1865 611400 |
| andrew.pollard@paediatrics.ox.ac.uk |
Public
Oxford Vaccine Group
Churchill Hospital
Centre for Vaccinology and Tropical Medicine
Oxford
OX3 7LE
United Kingdom
| Phone | +44 (0)7468 353751 |
|---|---|
| sarah.kelly@paediatrics.ox.ac.uk |
Study information
| Study design | Multi-site randomized 5-arm non-inferiority clinical trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Prevention |
| Participant information sheet | ISRCTN60356654_PIS_English_V2.1_17Feb2020.pdf |
| Scientific title | Optimising diphtheria, tetanus toxoids and pertussis (DTP)-containing vaccine infant immunisation schedules in Uganda |
| Study acronym | OPTIMMS-Uganda |
| Study objectives | To identify an optimal immunisation schedule for infants by comparing the immunogenicity of 5 different immunisation schedules (each based on positive immunogenicity data from previous research) including the current WHO recommended 'accelerated' schedule, investigating the effect of number, spacing and timing of doses of routine infant vaccines in the different schedule using the WHO recommended EPI schedule as the reference schedule |
| Ethics approval(s) | 1. Approved 16/12/2019, Uganda Virus Research Institute (UVRI) Research Ethics Committee (Plot 51-59, Nakiwogo Rd, Entebbe, Uganda; +256 414 320 385; fayebazibwe@uvri.go.ug), ref: GC/127/19/12/754 2. Approved 24/07/2020, Uganda National Council for Science & Technology (UNSCT, Plot 6 Kimera Road, Ntinda, P.O. Box 6884, Kampala, Uganda; +256 414 705500; info@unsct.go.ug), ref: SS 5205 3. Approved 04/02/2021, National Drug Authority (Plot 19 Lumumba Avenue, P.O. Box 23096, Kampala, Uganda; +256 417 788 100/1; ndaug@nda.or.ug), ref 686/NDA/DPS/09/2020. 4. Approved 03/03/2021, OxTREC (Research Services, University Of Oxford, University Offices, Oxford, OX1 2JD, UK; +44 (0)1865 282585; oxtrec@admin.ox.ac.uk), ref: 13-20. |
| Health condition(s) or problem(s) studied | Diphtheria, tetanus toxoids and pertussis (DTP) immunity through infant immunisation schedules in Uganda |
| Intervention | Infants will be enrolled at study “hub” sites, located in busy and centrally located health facilities and clinics, in Masaka District, Uganda. Potential participants will be identified throughout a broader catchment area, through antenatal clinics (ANC), and early vaccination visits, and invited to come of one of the hub sites to enrol in the study, if interesteds. The study will be open-label for participants and clinical trial staff but blinded for laboratory staff. The study will assess the immunogenicity of the current DTP-Hib-HBV-containing vaccine administered in 5 different immunisation schedules Following informed parent/legal guardian consent, enrolled infants will be randomly allocated to one of 5 main vaccination groups, and one of four booster dose schedule. Randomisation will occur electronically via a plugin on RedCAP. The first two schedules (Groups 1 and 2) are two 'Early Pertussis' schedules and correspond to the WHO standard, and a modified, EPI schedules (two rather than 3 early doses). Group 3 will be vaccinated according to the OptImms-proposed schedule (which is also the E-CDC recommended schedule). Groups 4 and 5 correspond to the programs currently in use in the UK and Americas. Blood tests will be performed at standard time points considered necessary for evaluation of vaccine responses. The primary outcome Pertussis IgG immune response will be measured at the pre-booster dose time point, at 9 or 12 months of age. Children will receive varicella and typhoid vaccination as a benefit of participation in the study. Vaccinations will occur over a 15-month time period, with a 24-month follow-up period for all study arms. |
| Intervention type | Biological/Vaccine |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | DTwP-HBV-Hib vaccine (Serum Institute of India), Oral Polio Vaccine – Bi-valent, Injectable Polio Vaccine, Pneumococcal conjugate vaccine (Synflorix), Measles Rubella vaccine, Typhoid conjugate vaccine (Typbar-TCV®, Bharat-Biotech.), Yellow fever vaccine (Stamaril live attenuated, Sanofi Pasteur) |
| Primary outcome measure | Pertussis IgG immune response measured using Multiplexed Immune Assay (MIA)-5 plex at the pre-booster dose time point (aged 9 or 12 months) |
| Secondary outcome measures | Current secondary outcome measures as of 28/06/2024: 1. Pertussis IgG immune response measured using MIA 4-plex at the post-prime dose time point, (aged 10, 12, 14 or 16 weeks), 1 month post-primary series (aged 18, 20, or 28 weeks), pre-booster timepoint (aged 9 or 12 months), post-booster timepoint (aged 10 or 13 months), and aged 24 months 2. Diphtheria IgG immune response measured using MIA 5-plex using in-house reference sera calibrated against the WHO standard, at age 14 or 16 weeks, 1 month post-primary series (aged 18, 20, or 28 weeks), pre-booster timepoint (aged 9 or 12 months), post-booster timepoint (aged 10 or 13 months), and aged 24 months. The MIA 5-plex uses in-house reference sera as standard, which are calibrated against the WHO standard. 3. Tetanus IgG immune response measured using MIA 5-plex using in-house reference sera calibrated against the WHO standard, at age 14 or 16 weeks, 1 month post-primary series (aged 18, 20, or 28 weeks), pre-booster timepoint (aged 9 or 12 months), post-booster timepoint (aged 10 or 13 months), and aged 24 months 4. Hepatitis B virus S antigen measured using an assay currently under development at the Dutch Institute of Public Health, at age 14 or 16 weeks, 1 month post-primary series (aged 18, 20, or 28 weeks), pre-booster timepoint (aged 9 or 12 months), post-booster timepoint (aged 10 or 13 months), and aged 24 months 5. Polyribosylribitol phosphate (PRP) Haemophilus influenzae type b (Hib) IgG immune response measured using a multiplexed immune assay, at age 14 or 16 weeks, 1 month post-primary series (aged 18, 20, or 28 weeks), pre-booster timepoint (aged 9 or 12 months), post-booster timepoint (aged 10 or 13 months), and aged 24 months 6. Serotype specific anti-pneumococcal IgG measured in an MIA x-plex, in 1a, 2, 3 and 4 blood samples in all arms and booster groups . IVIG that has been calibrated against the 89-S serum is used as reference serum 7. Polio type I-III IgG immune response measured using a 3-plex inhibition assay, at the pre-booster timepoint (aged 9 or 12 months) and aged 24 months 8. Typhoid vi-IgG will be measured using an assay currently under development at the Dutch Institute of Public Health, in blood 2 in Arm 5 at 28 weeks , in blood 3&4b in booster group 2, 3, and 4 (12 and 24 months). 9. Serum volumes permitting YF response will be measured using plaque reduction neutralization titre (PRNT) assays, by ELISA and/or indirect fluorescent antibody test (IFA) in blood 2 in Arm 5 at 28 weeks , in blood 3&4b in booster group 2, 3, and 4 (12 and 24 months). 10. Measles IgG antibody concentrations are measured in an MIA 4-plex at all time points up to the first measles and rubella vaccine dose, if possible given blood sample volumes 11. Measles titre measured using plaque reduction neutralization titre (PRNT) assay, if possible given blood sample volume, at all time points up to the first measles and rubella vaccine dose 12. Rubella IgG response measured using MIA 4-plex, if possible given blood sample volume, at all time points up to the first measles and rubella vaccine dose. As standard, the international rubella standard (RUBI-1-94) is used, which has been calibrated against the international reference serum for measles. 13. Descriptive summary of self-reported local and systemic vaccine reactions occurring within 7 days post-vaccination collected verbally at each point of contact, using Brighton Collaboration case definitions 14. Rota virus IgG will be measured using MIA 4-plex in all blood samples of all arms and booster groups. 15. SARS-COV2 IgG and RSV IgG will be measured using MIA 4-plex in all blood samples of all arms and booster groups. _____ Previous secondary outcome measures: 1. Pertussis IgG immune response measured using MIA 4-plex at the post-prime dose time point, (aged 10, 12, 14 or 16 weeks), 1 month post-primary series (aged 18, 20, or 28 weeks), pre-booster timepoint (aged 9 or 12 months), post-booster timepoint (aged 10 or 13 months), and aged 24 months 2. Diphtheria IgG immune response measured using MIA 5-plex using in-house reference sera calibrated against the WHO standard, at age 14 or 16 weeks, 1 month post-primary series (aged 18, 20, or 28 weeks), pre-booster timepoint (aged 9 or 12 months), post-booster timepoint (aged 10 or 13 months), and aged 24 months. The MIA 5-plex uses in-house reference sera as standard, which are calibrated against the WHO standard. 3. Tetanus IgG immune response measured using MIA 5-plex using in-house reference sera calibrated against the WHO standard, at age 14 or 16 weeks, 1 month post-primary series (aged 18, 20, or 28 weeks), pre-booster timepoint (aged 9 or 12 months), post-booster timepoint (aged 10 or 13 months), and aged 24 months 4. Hepatitis B virus S antigen measured using an assay currently under development at the Dutch Institute of Public Health, at age 14 or 16 weeks, 1 month post-primary series (aged 18, 20, or 28 weeks), pre-booster timepoint (aged 9 or 12 months), post-booster timepoint (aged 10 or 13 months), and aged 24 months 5. Polyribosylribitol phosphate (PRP) Haemophilus influenzae type b (Hib) IgG immune response measured using a multiplexed immune assay, at age 14 or 16 weeks, 1 month post-primary series (aged 18, 20, or 28 weeks), pre-booster timepoint (aged 9 or 12 months), post-booster timepoint (aged 10 or 13 months), and aged 24 months 6. Serotype specific anti-pneumococcal IgG measured in an MIA x-plex, at the pre-booster timepoint (aged 9 months), post-booster timepoint (aged 10 months), and aged 24 months. IVIG that has been calibrated against the 89-S serum is used as reference serum 7. Polio type I-III IgG immune response measured using a 3-plex inhibition assay, at the pre-booster timepoint (aged 9 or 12 months) and aged 24 months 8. Typhoid vi-IgG will be measured using an assay currently under development at the Dutch Institute of Public Health, at age 13 and 24 months 9. Serum volumes permitting JE response will be measured using plaque reduction neutralization titre (PRNT) assays, by ELISA and/or indirect fluorescent antibody test (IFA) at age 13 and 24 months 10. Measles IgG antibody concentrations are measured in an MIA 4-plex at all time points up to the first measles and rubella vaccine dose, if possible given blood sample volumes 11. Measles titre measured using plaque reduction neutralization titre (PRNT) assay, if possible given blood sample volume, at all time points up to the first measles and rubella vaccine dose 12. Rubella IgG response measured using MIA 4-plex, if possible given blood sample volume, at all time points up to the first measles and rubella vaccine dose. As standard, the international rubella standard (RUBI-1-94) is used, which has been calibrated against the international reference serum for measles. 13. Descriptive summary of self-reported local and systemic vaccine reactions occurring within 7 days post-vaccination collected verbally at each point of contact, using Brighton Collaboration case definitions |
| Overall study start date | 24/06/2019 |
| Completion date | 30/06/2024 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Child |
| Lower age limit | 42 Days |
| Upper age limit | 50 Days |
| Sex | Both |
| Target number of participants | 956 |
| Key inclusion criteria | 1. Aged between 42 and 50 days at the time of the first visit 2. Generally healthy as determined by a medical history and examination 3. Resident in the greater Masaka, Uganda study area and planning to remain in the study area for the 2 years of the study |
| Key exclusion criteria | 1. Born at <37 weeks gestation 2. Birth weight <2.5 kg, or a current weight of <3 kg at 6 weeks of age, as determined by a medical professional 3. Prior receipt of any vaccination except polio, hepatitis B, or BCG 4. Planned administration of vaccines other than the study vaccines (with the exception of vaccines against rotavirus, hepatitis A & B, inactivated influenza and varicella, which can be administered 14 days before or after study vaccines; polio and measles/rubella vaccines as part of national campaigns; and BCG vaccines which will be administered when indicated by national programme) 5. Parents who plan to move out of the geographical study area 6. Concurrently participating in another clinical study, which includes blood draws or IMPs, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device) 7. Any major congenital defects, serious chronic illness, significant disease, disorder, family history or diagnosis of immunosuppressive condition, or medical treatments which, in the opinion of the Investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant’s ability to participate in the study 8. Use of any investigational or non-registered product (drug or vaccine) within 30 days preceding the vaccination, or planned use during the study period 9. Known allergy to any vaccine components |
| Date of first enrolment | 01/10/2021 |
| Date of final enrolment | 31/07/2022 |
Locations
Countries of recruitment
- Uganda
Study participating centre
Nakiwogo Road
Entebbe
-
Uganda
Sponsor information
University/education
Oxford Tropical Research Ethics Committee
Research Services
Wellington Square
Oxford
OX1 2JD
England
United Kingdom
| Phone | +44 (0)1865 282585 |
|---|---|
| oxtrec@admin.ox.ac.uk | |
| Website | https://researchsupport.admin.ox.ac.uk/governance/ethics/committees/oxtrec |
"ROR" |
https://ror.org/052gg0110 |
Funders
Funder type
Charity
Government organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- Bill & Melinda Gates Foundation, Gates Foundation, BMGF, B&MGF, GF
- Location
- United States of America
Results and Publications
| Intention to publish date | 31/07/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal. End of study report intended to be available for the funder 30/5/2024. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are not expected to be made available due to their size, but analyses will be published with summary data. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | version V2.1 | 17/02/2020 | 01/03/2021 | No | Yes |
| Participant information sheet | version 3.0 | 24/02/2021 | 11/02/2022 | No | Yes |
| Protocol article | 21/07/2023 | 24/07/2023 | Yes | No |
Additional files
- ISRCTN60356654_PIS_English_V2.1_17Feb2020.pdf
- Uploaded 01/03/2021
- ISRCTN60356654 PIS V3.0 24Feb2021.pdf
Editorial Notes
28/06/2024: The secondary outcome measures were changed.
15/03/2024: The following changes were made:
1. The overall study end date was changed from 13/02/2024 to 30/06/2024.
2. The intention to publish date was changed from 01/01/2025 to 31/07/2025.
24/07/2023: Publication reference added.
11/02/2022: The following changes were made to the trial record:
1. The recruitment end date was changed from 28/02/2022 to 31/07/2022.
2. The participant information sheet v3.0 was uploaded as an additional file.
01/10/2021: The following changes were made to the trial record:
1. The recruitment start date was changed from 13/09/2021 to 01/10/2021.
2. The public contact was changed.
06/09/2021: The recruitment start date was changed from 03/09/2021 to 13/09/2021.
26/08/2021: The recruitment start date has been changed from 31/08/2021 to 03/09/2021.
14/07/2021: The recruitment start date was changed from 12/07/2021 to 31/08/2021.
04/06/2021: The recruitment start date was changed from 21/06/2021 to 12/07/2021.
12/05/2021: The recruitment start date was changed from 31/05/2021 to 21/06/2021.
10/05/2021: The recruitment start date was changed from 03/05/2021 to 31/05/2021.
14/04/2021: The recruitment start date was changed from 19/04/2021 to 03/05/2021.
16/03/2021: The following changes were made to the trial record:
1. The recruitment start date was changed from 16/03/2021 to 19/04/2021.
2. The ethics approval (4) was added.
01/03/2021: The participant information sheet has been uploaded as an additional file.
15/02/2021: Trial’s existence confirmed by Uganda National Council for Science & Technology.
