A Phase 4 interventional study of PCV10 full dose and PCV10 fractional dose in Pneumococcal Carriage, sponsored by Epicentre. Completed at 1 site in Niger. Open to participants aged 1 Year to 9 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-12-05.
Sponsored by Epicentre · Phase 4, Interventional, and Prevention
The aim of this study is to assess the impact of a mass campaign with a single, fractional dose of Pneumosil®, a PCV10, on VT carriage. A 20% fractional dose (1/5th) will be used as a practical formulation to prepare and administer. This study will assess whether the impact of a single fractional dose mass campaign on carriage is non-inferior to a single full dose mass campaign in a cluster randomized trial in a low coverage setting in Niger. The results would provide evidence of the population-level direct and indirect impact of fractional dose in older children which will be completed by mathematical modelling, to inform the policy debate regarding PCV dosing schedules in different contexts. This trial and the modelling exercises that follow, would allow for larger scale evaluation of fractional dose PCV strategies in multiple contexts.
In 2015, there were an estimated 8.9 million cases (uncertainty range 7.7-10.6 million) of clinical pneumococcal pneumonia globally, with 2.4 million cases estimated in Africa alone (uncertainty range 2.1-3.1 million). These figures represent a global reduction of 37% from 14.2 million cases (12.3 million-16.9 million) in 2000. However, pneumococcal disease continues to be a leading cause of severe disease and death representing 10% of all death in children under 5 years of age (1). These deaths occur disproportionally in low- and middle-income countries (LMICs), with approximately 50% of global pneumococcal deaths estimated to occur in 4 countries: India, Nigeria, Pakistan and the Democratic Republic of Congo.
Vaccination campaigns targeting children up to 5 years of age have an effect in the reduction of VT carriage disease. However, in crises or settings with high prevalence of malnutrition, the high pneumococcal carriage prevalence is likely to extend to older age groups. Single dose vaccination of a larger age group might be needed to control VT circulation. Currently, for GAVI-supported countries such as Niger, PCV13 vaccine has a cost of US$3 per dose. Pneumosil®, a PCV10 manufactured by Serum institute of India Ltd has the lowest price of all WHO prequalified vaccines, at US$2 per dose.
Mass campaigns targeting large groups require many doses and might not be sustainable over time. Fractional doses of PCV could be a solution to overcome the high PCV costs, increase vaccine access and expand vaccination benefits through alternative strategies. The study population (ages 1-9) stems from an LSHTM modelling study.
Objectives of the study Primary objective: evaluate whether the full dose of PCV is superior to the absence of vaccine and then if a single 20% dose of PCV is non-inferior to a full dose in carriage reduction.
Secondary objectives:
Note: the 1-9 years age group targeted for the mass campaign is based on data from a model in Kilifi, Kenya. Baseline carriage survey data together with data will be used on interactions between age groups and PCV coverage data collected during the baseline survey, to estimate the age group that should be targeted for vaccination.
Methodology A cluster-randomized, blinded, non-inferiority trial will be implemented in rural villages of the Madarounfa District of Niger. Clusters will be randomized to full dose, fractional dose or control arm in 2:2:1 allocation ratio. Clusters will be composed of a village or group of neighbouring villages that share a school or market. Stratified randomization will be used to consider size of clusters and proximity to health centre. Vaccination will target all children aged approximately 1 to 9 years of age residing in the selected villages Prior to the mass vaccination campaign, a cross-sectional survey will be implemented to estimate community-level carriage of VT pneumococci, as well as to collect data on household composition, social interactions and PCV vaccination coverage.
Epicentre is the lead sponsor of 49 studies on the registry; 6 are open to participants now.
Counted across the registry records on this site, refreshed daily.
For participation in pneumococcal carriage surveys:
Inclusion criteria:
Exclusion criteria:
For participation in mass vaccination campaigns (with full or fractional dose PCV10)
Inclusion criteria:
Exclusion criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
27 clusters randomized to receive a vaccination campaign with the full dose.
Biological: PCV10 full dose
27 clusters randomized to receive a vaccination campaign with the fractional dose (1/5).
Biological: PCV10 fractional dose
9 clusters randomized to the control arm.
Mass vaccination campaign with one single dose PCV10 vaccine administered as a full dose.
Mass vaccination campaign with one single dose PCV10 vaccine administered as a fractional dose.
Effect of a Single Dose PCV10 Campaign in the Reduction of VT Carriage
The effect of a single dose PCV10 campaign in the reduction of VT carriage will be assessed by: first, assessing the superiority of a campaign using full doses of PCV10 compared to control group without vaccination; and second, by establishing the non-inferiority of a campaign using fractional doses of PCV10 compared to a campaign using full doses. NP carriage will be measured in the 3 study arms (full dose arm, fractional dose arm and control arm) in a baseline survey implemented prior to the vaccination campaign and in a post-vaccination survey. The NP carriage of VT S. pneumoniae will be measured as the proportion of participants that are colonized with any of the 10 serotypes covered by PCV10 at each time point. The reduction in NP carriage will be calculated by comparing the proportion of children carrying VT pneumococci 6 months post-vaccination to baseline, at the time of vaccination. The prevalence of colonization of non-VT serotypes will also be described at both timepoints.
Time frame: During three months of vaccination campaign, and 6 months post-vaccination campaign
Vaccine Safety Monitoring
Vaccine safety will be monitored up to 28 days after vaccination and all AEs and SAEs will be recorded.
Time frame: Up to 28 days after vaccination
Cost-effectiveness and Modeling
An age-structured, dynamic, deterministic model of pneumococcal transmission will be constructed to estimate the impact of mass fractional dose PCV campaigns on VT carriage. The model will use the data on social interactions between age groups and PCV coverage estimates collected during the baseline survey as well as the results of the VT carriage from the baseline survey. Based on the modeled epidemiological impact of PCV10 mass campaigns, with both full and fractional doses, a cost-effectiveness analysis will be performed to estimate the incremental cost-effectiveness ratio of routine PCV10 mass campaigns. The modeled epidemiological impact and cost-effectiveness of a fractional dose mass campaign will be used to inform ongoing discussions of dose-sparing strategies and the use of single-dose fractional PCV in acute humanitarian emergencies.
Time frame: Within 2 years of study start.
Facilitators and Barriers to Implementing Mass Campaigns of Fractional Dose PCV
A qualitative study will be conducted among parents, healthcare workers, national and international stakeholders to develop insights and recommendations on how a potential future fractional dose PCV mass campaign could be successfully planned, communicated, delivered and integrated into national immunization programs.
Time frame: Within 2 years of study start.
| Milestone | Single Full Dose of PCV 10 | Single Fractional Dose of PCV10 (1/5) | Control Group |
|---|---|---|---|
| Started | 20091 | 18821 | 5706 |
| Completed | 20091 | 18821 | 5706 |
| Not completed | 0 | 0 | 0 |
The effect of a single dose PCV10 campaign in the reduction of VT carriage will be assessed by: first, assessing the superiority of a campaign using full doses of PCV10 compared to control group without vaccination; and second, by establishing the non-inferiority of a campaign using fractional doses of PCV10 compared to a campaign using full doses. NP carriage will be measured in the 3 study arms (full dose arm, fractional dose arm and control arm) in a baseline survey implemented prior to the vaccination campaign and in a post-vaccination survey. The NP carriage of VT S. pneumoniae will be measured as the proportion of participants that are colonized with any of the 10 serotypes covered by PCV10 at each time point. The reduction in NP carriage will be calculated by comparing the proportion of children carrying VT pneumococci 6 months post-vaccination to baseline, at the time of vaccination. The prevalence of colonization of non-VT serotypes will also be described at both timepoints.
| Percentage of participants | Single Full Dose of PCV 10 | Single Fractional Dose of PCV10 (1/5) | Control Group |
|---|---|---|---|
| Effect of a Single Dose PCV10 Campaign in the Reduction of VT Carriage | 4.6 | 8.0 | 16.5 |
Vaccine safety will be monitored up to 28 days after vaccination and all AEs and SAEs will be recorded.
Results for this outcome have not been posted.
An age-structured, dynamic, deterministic model of pneumococcal transmission will be constructed to estimate the impact of mass fractional dose PCV campaigns on VT carriage. The model will use the data on social interactions between age groups and PCV coverage estimates collected during the baseline survey as well as the results of the VT carriage from the baseline survey. Based on the modeled epidemiological impact of PCV10 mass campaigns, with both full and fractional doses, a cost-effectiveness analysis will be performed to estimate the incremental cost-effectiveness ratio of routine PCV10 mass campaigns. The modeled epidemiological impact and cost-effectiveness of a fractional dose mass campaign will be used to inform ongoing discussions of dose-sparing strategies and the use of single-dose fractional PCV in acute humanitarian emergencies.
Results for this outcome have not been posted.
A qualitative study will be conducted among parents, healthcare workers, national and international stakeholders to develop insights and recommendations on how a potential future fractional dose PCV mass campaign could be successfully planned, communicated, delivered and integrated into national immunization programs.
Results for this outcome have not been posted.
Collected over Adverse event data were collected for 28 days following vaccination.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Single Full Dose of PCV 10 | 3/20,091 (0%) | 28/20,091 (0.1%) | 0/20,091 (0%) |
| Single Fractional Dose of PCV10 (1/5) | 4/18,821 (0%) | 33/18,821 (0.2%) | 0/18,821 (0%) |
| Control Group | 1/5,706 (0%) | 19/5,706 (0.3%) | 0/5,706 (0%) |
| Event | Single Full Dose of PCV 10 | Single Fractional Dose of PCV10 (1/5) | Control Group |
|---|---|---|---|
| MalariaInfections and infestations | 18/20091 | 22/18821 | 13/5706 |
| PneumoniaInfections and infestations | 2/20091 | 1/18821 | 2/5706 |
| KwashiorkorMetabolism and nutrition disorders | 2/20091 | 3/18821 | 2/5706 |
| GastroenteritisInfections and infestations | 2/20091 | 5/18821 | 1/5706 |
| DiarrheaGastrointestinal disorders | 1/20091 | 0/18821 | 1/5706 |
| Respiratory tract infectionInfections and infestations | 2/20091 | 0/18821 | 0/5706 |
| Osteomyelitis acuteInfections and infestations | 0/20091 | 1/18821 | 0/5706 |
| MarasmusMetabolism and nutrition disorders | 0/20091 | 1/18821 | 0/5706 |
| Mucocutaneous candidiasisInfections and infestations | 1/20091 | 0/18821 | 0/5706 |
| Age, Continuous(years) | Single Full Dose of PCV 10 | Single Fractional Dose of PCV10 (1/5) | Control Group | Total |
|---|---|---|---|---|
| Mean | 4.5 ± 0.5 | 4.3 ± 0.6 | 4.5 ± 0.6 | 4.4 ± 0.6 |
| Sex: Female, Male(Participants) | Single Full Dose of PCV 10 | Single Fractional Dose of PCV10 (1/5) | Control Group | Total |
|---|---|---|---|---|
| Female | 482 | 473 | 157 | 1112 |
| Male | 473 | 475 | 163 | 1111 |
| Race and Ethnicity Not Collected(Participants) | Single Full Dose of PCV 10 | Single Fractional Dose of PCV10 (1/5) | Control Group | Total |
|---|---|---|---|---|
| Count of participants | — | — | — | 0 |
| Region of Enrollment(participants) | Single Full Dose of PCV 10 | Single Fractional Dose of PCV10 (1/5) | Control Group | Total |
|---|---|---|---|---|
| Niger | 955 | 948 | 320 | 2223 |
| Baseline prevalence of VT pneumococcal carriage(Percentage of participants) | Single Full Dose of PCV 10 | Single Fractional Dose of PCV10 (1/5) | Control Group | Total |
|---|---|---|---|---|
| Number | 15.6 | 17.9 | 18.8 | 17.0 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — IPD will consist of sociodemographic data collected in baseline and post-vaccination surveys, as well as results of pneumococcal isolation and serotyping.
Time frame: De-identified IPD will be available after final data collection and cleaning, and once laboratory quality control procedures have been conducted.
Access criteria: Any interested party may request access to the data for the purposes of secondary analysis or meta-analysis. The process for requesting data, and the criteria upon which requests will be judged are described in Epicentre Standard Operating Procedures.
This study is completed, as verified in Nov 2024. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: 10-valent pneumococcal conjugate vaccine
Epicentre