Mass Campaigns With Fractional Dose Pneumococcal Vaccines in Sub-Saharan Africa (fPCV)

NCT ID: NCT05175014

Last Updated: 2024-12-05

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

44618 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-12-30

Study Completion Date

2023-10-03

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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:

* To measure the age-stratified prevalence of NP carriage of S. pneumoniae in children 1-9 years of age in the study area.
* To determine the impact of a mass vaccination campaign with one full dose of PCV in children 1 to 9 years of age on VT pneumococci carriage 6 months after vaccination
* To assess the occurrence of adverse events (AE) and serious adverse events (SAE) during 28 days after administration of fractional and full doses and SAEs throughout the duration of follow-up
* To model the potential impact of fractional dose PCV campaigns in other contexts using the results of the clinical trial.
* To develop recommendations on how a potential future fractional dose PCV mass campaign could be successfully planned, communicated, delivered, and integrated into national immunization programmes using qualitative analysis.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Pneumococcal Carriage

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

A Phase IV, 3-arm, observer-blinded, cluster-randomized controlled trial
Primary Study Purpose

PREVENTION

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors
Vaccinators will not be blinded, but participants will not know vaccine dosage allocation. Laboratory staff (outcome assessors) will be blinded to their group allocation.

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Single full dose of PCV 10

27 clusters randomized to receive a vaccination campaign with the full dose.

Group Type EXPERIMENTAL

PCV10 full dose

Intervention Type BIOLOGICAL

Mass vaccination campaign with one single dose PCV10 vaccine administered as a full dose.

Single fractional dose of PCV10 (1/5)

27 clusters randomized to receive a vaccination campaign with the fractional dose (1/5).

Group Type EXPERIMENTAL

PCV10 fractional dose

Intervention Type BIOLOGICAL

Mass vaccination campaign with one single dose PCV10 vaccine administered as a fractional dose.

Control Group

9 clusters randomized to the control arm.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

PCV10 full dose

Mass vaccination campaign with one single dose PCV10 vaccine administered as a full dose.

Intervention Type BIOLOGICAL

PCV10 fractional dose

Mass vaccination campaign with one single dose PCV10 vaccine administered as a fractional dose.

Intervention Type BIOLOGICAL

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Aged 1-9 years
2. Residing in the villages included in the study
3. Parent or caretaker provides informed consent for the child to participate in the study


1. Aged 1-9 years
2. Residing in the villages included in the study and allocated to vaccination
3. Head of the household or main caretaker provides consent for the child to be vaccinated

Exclusion Criteria

1. Head or facial injuries that contraindicate nasopharyngeal swabbing
2. Any condition or criteria, including acute or chronic clinically significant abnormality that in the opinion of the investigator might compromise the wellbeing of the participant or interfere with the outcome of the study

For participation in mass vaccination campaigns (with full or fractional dose PCV10)


1. Hypersensitivity to any component of the vaccine, including diphtheria toxoid
2. Vaccination with a PCV vaccine within the previous 4 weeks, as there should be a minimum of 4 weeks between doses
3. Moderate or severe febrile illness (temperature ≥39°C) is a temporal contraindication and the child should not be vaccinated until improvement
4. Any condition or criteria, including acute or chronic clinically significant abnormality that in the opinion of the clinical staff might compromise the wellbeing of the volunteer
Minimum Eligible Age

1 Year

Maximum Eligible Age

9 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

London School of Hygiene and Tropical Medicine

OTHER

Sponsor Role collaborator

Kenya Medical Research Institute

OTHER

Sponsor Role collaborator

Universite Abdou Moumouni de Niamey, Niger

OTHER

Sponsor Role collaborator

Epicentre

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Dr. Rebecca Grais

Role: STUDY_DIRECTOR

Epicentre Research Department Director

Dr. Matthew Coldiron

Role: PRINCIPAL_INVESTIGATOR

Epicentre Research Department Investigator

Dr. Issaka Soumana

Role: PRINCIPAL_INVESTIGATOR

Epicentre Niger Research Center Assistant Manager

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Epicentre

Maradi, , Niger

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Niger

References

Explore related publications, articles, or registry entries linked to this study.

Coldiron ME, Soumana I, Baudin E, Langendorf C, Mamiafo Tchoula C, Brah S, Karani A, Gallagher KE, Kagucia EW, Scott JAG, Grais RF. Effect of mass campaigns with full and fractional doses of pneumococcal conjugate vaccine (Pneumosil) on the reduction of nasopharyngeal pneumococcal carriage in Niger: a three-arm, open-label, cluster-randomised trial. Lancet Infect Dis. 2025 Jun;25(6):634-642. doi: 10.1016/S1473-3099(24)00719-9. Epub 2025 Jan 8.

Reference Type DERIVED
PMID: 39798587 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

fPCV

Identifier Type: -

Identifier Source: org_study_id