Pneumonia, PneumococcalPhase 3NCT03896477

Study of 10-valent Pneumococcal Conjugate Vaccine (Pneumosil) Administered in a 2+1 Schedule to Healthy Infants

A Phase 3 study testing Pneumosil, Prevenar 13 and Synflorix in people with Pneumonia, Pneumococcal, run by PATH at 1 site in The Gambia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The primary objectives of this study are to evaluate the immunogenicity (antibody response) and safety and tolerability of a 2-dose primary series and booster dose (2+1 schedule) of Pneumosil co-administered with routine pediatric vaccines in healthy infants in The Gambia. Read more about this study

Who is it for?: Ages 42 to 56 daysHealthy volunteers can take part
Conditions the study is for: Pneumonia, Pneumococcal
What is being tested?: Pneumosil, Prevenar 13 and Synflorix
Type of treatment: Vaccines
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 660 participants
Where: 1 siteThe Gambia
Study dates: 18 Jul 2019to 17 Dec 2020
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 42 to 56 days
All sexes
Healthy volunteers accepted
Child

Who may be able to join

Healthy infants based on medical history and clinical assessment.
Between 6 and 8 weeks (ie 42 to 56 days) old, inclusive.
Subject's parent must provide voluntary written/thumb-printed informed consent and be willing to comply with study requirements and procedures.
Subjects must have been born full-term, have a weight-to-height Z score of ≥ -2 at the time of enrollment (WHO child growth standard), and be ≥ 3.5 kg at randomization.
Subject's parents must be available for the duration of trial participation

Who cannot join

Use of any investigational medicinal product prior to randomization.
Previous vaccination against or infection with S. pneumoniae.
History of anaphylactic shock or an allergic reaction to any prior vaccination.
Any fever, illness (including malaria).
Receipt of another study vaccine within 30 days of study start.
Chronic administration of an immunosuppressant or administration of immunoglobulins

Show all 9Show fewer

History of blood disorder, primary immunodeficiency, or a sibling who has such a diagnosis or who died suddenly without apparent cause.
History of meningitis, seizures or any neurological disorder.
Exposure to human immunodeficiency virus (HIV) by history.

Trial locations and contacts

1 site in 1 country.

The Gambia1 site

Medical Research Council Unit, The Gambia at the London School of Hygiene and Tropical Medicine (MRCG at LSHTM)
Banjul

Other trials in The Gambia

About this study

Official title: A Phase 3, Randomized, Observer-Blind Study to Evaluate the Safety, Tolerability, Immunogenicity of Serum Institute of India's 10-Valent Pneumococcal Conjugate Vaccine (PNEUMOSIL®) Administered in a 2+1 Schedule to Healthy Infants in The Gambia

Read the detailed description

This study will provide data necessary to evaluate the safety and immunogenicity of Pneumosil when administered in an alternative schedule to the 3 dose primary schedule (3+0) evaluated in the Phase 3 pivotal trial (VAC-056; NCT03197376) - namely in a 2 dose primary and booster (2+1) schedule - and compare immunogenicity to that of both currently licensed second-generation pneumococcal conjugate vaccines (Synflorix and Prevenar 13) administered in the same 2+1 schedule.

In this prospective, single center, randomized, active-controlled, observer-blind, Phase 3 descriptive study, 660 healthy Gambian pneumococcal conjugate vaccine (PCV)-naïve infants will be randomized 1:1:1 to receive 3 doses of either Pneumosil, Synflorix or Prevenar 13 at 6 weeks, 14 weeks and 9-10 months of age. Standard Expanded Program on Immunization (EPI) vaccinations in The Gambia will be given concomitantly with all 3 doses of study vaccine.

The booster vaccination window was extended up to 18 months of age due to a pause in the study due to the coronavirus disease 2019 (COVID-19) pandemic. The study schedule for participants is as follows:

Age 6 weeks: First primary vaccination dose administered
Age 14 weeks: Second primary vaccination dose administered (8 weeks after first primary dose)
Age 18 weeks: Blood sample for immunogenicity testing (4 weeks after second primary dose)
Age 9-18 months: Blood sample for immunogenicity testing and booster vaccination dose administered
Age 10-19 months: Blood sample for immunogenicity testing (4 weeks after booster dose)

Conditions: Pneumonia, Pneumococcal
Being tested: Pneumosil, Prevenar 13, Synflorix
Medical subject headings: Pneumonia, Pneumococcal

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PneumosilBiological
Also called Serum Institute of India Pneumococcal conjugate vaccine (SIIPL-PCV )
One single dose contains 2 μg of polysaccharide for serotypes 1, 5, 6A, 7F, 9V, 14, 19A, 19F and 23F, and 4 μg for serotype 6B formulated with aluminium phosphate as an adjuvant in an appropriate buffer
Prevenar 13Biological
One single dose contains 2.2 µg of the following pneumococcal polysaccharides serotypes - 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F - and 4.4 µg of pneumococcal polysaccharide serotype 6B, all conjugated to CRM197 and absorbed onto aluminum phosphate
SynflorixBiological
Also called Pneumococcal polysaccharide conjugate vaccine (adsorbed)
One single dose contains 1 μg of polysaccharide for serotypes 1, 5, 6B, 7F, 9V, 14, and 23F, and 3μg of serotypes 4, 18C, and 19F formulated with aluminum phosphate as an adjuvant.

Study groups in NCT03896477
Study group	Role	What they receive
Pneumosil	Experimental	Infants received two primary vaccinations with Pneumosil, the first at age 6 weeks and the second at age 14 weeks. A booster vaccination was given between 9 and 16 months of age. Receives: Biological: Pneumosil
Synflorix	Active comparator	Infants received two primary vaccinations with Synflorix, the first at age 6 weeks and the second at age 14 weeks. A booster vaccination was given between 9 and 16 months of age. Receives: Biological: Synflorix
Prevenar 13	Active comparator	Infants received two primary vaccinations with Prevenar 13, the first at age 6 weeks and the second at age 14 weeks. A booster vaccination was given between 9 and 16 months of age. Receives: Biological: Prevenar 13

What is being measured

The primary outcome is the main question the study is designed to answer.

Geometric Mean Concentration (GMC) of Serotype-specific Immunoglobulin G (IgG) Antibodies Four Weeks Post-Booster
The IgG antibody concentration to each of the 10 serotypes contained in Pneumosil was measured by enzyme-linked immunosorbent assay (ELISA) in serum samples collected 4 weeks after the booster dose (Visit 6).
The pneumococcal serotype-specific IgG ELISAs were performed using the World Health Organisation (WHO) reference assay at the WHO Pneumococcal Serology Reference Laboratory, at the Institute of Child Health, University College London, United Kingdom (UK), where the assay was validated.
Measured: 4 weeks post booster dose
Number of Participants With Solicited Local and Systemic Adverse Events (AEs) Through Day 6 Following Any Vaccination
Solicited local reactions included tenderness, erythema/redness and induration/swelling at the study vaccine injection site.
Solicited systemic reactions included cutaneous rash, fever (based on axillary temperature), irritability, drowsiness, and decreased appetite.
The severity of all solicited AEs was graded from mild (Grade 1) to potentially life threatening (Grade 4), based on protocol-defined criteria that were derived from Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (Version 2.0, November 2014).
Measured: Day 0 to Day 6 after each vaccination
Number of Participants With Unsolicited Treatment-emergent Adverse Events (TEAEs)
AEs include any intercurrent illness or injury during the study, clinically significant worsening of a preexisting condition, and any solicited AE that occurred or was ongoing 6 days after study vaccine administration. A TEAE is an event that was not present prior to administration of the study vaccine, or increased in intensity after administration of the study vaccine.
Unsolicited AEs were graded using the scale below:
Grade 1: Mild; asymptomatic or mild symptoms; intervention not indicated.
Grade 2: Moderate; minimal, local, or noninvasive intervention indicated.
Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling.
Grade 4: Life-threatening consequences; urgent intervention indicated.
Grade 5: Death related to AE.
Related AEs are AEs where the Investigator determined a reasonable causal relationship between the vaccine administered and the AE based on medical judgement.
Measured: AEs were collected from first dose at age 6 weeks up to 9 months of age, and then from the date of the booster vaccination through 4 weeks post vaccination; approximately 8.5 months overall.
Number of Participants With Serious Adverse Events (SAEs)
An SAE was a specific AE that:
- Resulted in death.
- Was life-threatening.
- Required inpatient hospitalization or prolongation of an existing hospitalization.
- Resulted in a persistent or significant disability or incapacity.
- Resulted in a congenital anomaly or birth defect
Measured: SAEs were collected from first dose at age 6 weeks up to 4 weeks post booster vaccination, approximately 15.5 months overall.

Secondary outcomes (14)

Geometric Mean Titers (GMT) of Serotype-specific Opsonophagocytic Activity (OPA) Four Weeks Post-Booster
The functional activity of the antibody response to the 10 serotypes contained in Pneumosil was determined in serum samples collected 4 weeks after the booster dose in a subset of 50 participants per group. This activity was determined using the 4-fold multiplexed opsonophagocytic assay (MOPA) developed at the University of Alabama at Birmingham, and performed at the WHO Pneumococcal Serology Reference Laboratory, at the Institute of Child Health, University College London, UK, where the assay was validated.
A higher titer indicates increased antibody-mediated opsonophagocytosis.
Measured: 4 weeks post booster dose
Percentage of Participants With Serotype-specific Serum IgG Antibody Concentrations ≥ 0.35 μg/mL Four Weeks Post-Booster
The seroresponse rate was defined as the percentage of infants with serotype-specific IgG antibody concentrations of at least 0.35 μg/mL, which is the reference concentration for assessment of vaccine efficacy against invasive pneumococcal diseases (IPDs).
The IgG concentration to each of the 10 serotypes contained in Pneumosil was measured by ELISA in serum samples collected 4 weeks after the booster dose.
Measured: 4 weeks post booster dose
Percentage of Participants With Serotype-specific Serum IgG Antibody Concentrations ≥ 1.0 μg/mL Four Weeks Post-Booster
Seroresponse rate was also defined as the percentage of infants with serotype-specific IgG antibody concentrations of at least 1.0 μg/mL.
The IgG concentration to each of the 10 serotypes contained in Pneumosil was measured by ELISA in serum samples collected 4 weeks after the booster dose.
Measured: 4 weeks post booster dose
Percentage of Participants With Serotype-specific Serum OPA Titers ≥ 8 Four Weeks Post-Booster
The OPA seroresponse rate was defined as the percentage of infants with an OPA titer of at least 8.
Opsonophagocytic activity was measured using the 4-fold multiplexed opsonophagocytic assay (MOPA) from serum samples taken 4 weeks after the booster vaccination.
Measured: 4 weeks post booster dose
Percentage of Participants With Serotype-specific Serum IgG Antibody Concentrations ≥ 0.35 μg/mL Four Weeks After Completion of Primary Vaccinations
The seroresponse rate was defined as the percentage of infants with serotype-specific IgG antibody concentrations of at least 0.35 μg/mL, which is the reference concentration for assessment of vaccine efficacy against invasive pneumococcal diseases (IPDs).
The IgG concentration to each of the 10 serotypes contained in Pneumosil was measured by ELISA in serum samples collected 4 weeks after the second primary vaccination dose.
Measured: 4 weeks after completion of primary vaccinations (at age 18 weeks)
Geometric Mean Concentration of Serotype-specific IgG Antibodies Four Weeks After Completion of Primary Vaccinations
The IgG antibody concentration to each of the 10 serotypes contained in Pneumosil was measured by ELISA in serum samples collected 4 weeks after the second primary vaccination dose.
Measured: 4 weeks after completion of primary vaccinations (at age 18 weeks)
Percentage of Participants With Serotype-specific Serum OPA Titers ≥ 8 Four Weeks After Completion of Primary Vaccinations
The OPA seroresponse rate was defined as the percentage of infants with an OPA titer of at least 8.
Opsonophagocytic activity was measured using the 4-fold multiplexed opsonophagocytic assay (MOPA).
Measured: 4 weeks after completion of primary vaccinations (at age 18 weeks)
Geometric Mean Titers of Serotype-specific Serum OPA Four Weeks After Primary Vaccinations
Opsonophagocytic activity was measured using the 4-fold multiplexed opsonophagocytic assay (MOPA).
Measured: 4 weeks after completion of primary vaccinations (at age 18 weeks)
Percentage of Participants With Serotype-specific Serum IgG Concentrations ≥ 0.35 μg/mL Prior to Booster
The seroresponse rate was defined as the percentage of infants with serotype-specific IgG concentrations of at least 0.35 μg/mL, which is the reference concentration for assessment of vaccine efficacy against invasive pneumococcal diseases (IPDs).
The IgG concentration to each of the 10 serotypes contained in Pneumosil was measured by ELISA in serum samples collected immediately prior to the booster vaccination dose.
Measured: Prior to the booster dose at approximately 9 to 16 months of age
Geometric Mean Concentration of Serotype-specific Serum IgG Antibodies Prior to Booster
The IgG antibody concentration to each of the 10 serotypes contained in Pneumosil was measured by ELISA in serum samples collected immediately prior to the booster vaccination dose.
Measured: Prior to the booster dose at approximately 9 to 16 months of age
Percentage of Participants With Serotype-specific Serum OPA Titers ≥ 8 Prior to Booster
The OPA seroresponse rate was defined as the percentage of infants with an OPA titer of at least 8.
Opsonophagocytic activity was measured using the 4-fold multiplexed opsonophagocytic assay (MOPA) from serum samples collected immediately prior to the booster vaccination dose.
Measured: Prior to the booster dose at approximately 9 to 16 months of age
Geometric Mean Titer of Serotype-specific Serum OPA Prior to Booster
Opsonophagocytic activity was measured using the 4-fold multiplexed opsonophagocytic assay (MOPA) from serum samples collected immediately prior to the booster vaccination dose.
Measured: Prior to the booster dose at approximately 9 to 16 months of age
Ratio of Serotype-specific Serum IgG GMC 4 Weeks Post-Booster to Serotype-specific IgG GMC 4 Weeks After Completion of Primary Vaccinations
Booster response was measured by the ratio of IgG GMCs measured at the post-booster visit to those measured 4 weeks after completion of primary vaccinations.
Measured: 4 weeks after completion of primary vaccinations (at age 18 weeks) and 4 weeks post booster
Ratio of Serotype-specific Serum OPA GMT 4 Weeks Post-Booster to Serotype-specific OPA GMT 4 Weeks After Completion of Primary Vaccinations
OPA booster response was measured by the ratio of OPA GMTs measured at the post-booster visit to those measured 4 weeks after completion of primary vaccinations.
Measured: 4 weeks after completion of primary vaccinations (at age 18 weeks) and 4 weeks post booster

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

18 Jul 201917 Dec 2020

First posted1 Apr 2019
Study start18 Jul 2019
Primary completion17 Dec 2020
Study completion17 Dec 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Pneumonia, PneumococcalStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 660 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03896477
Sponsor's protocol ID: CVIA-074
Other IDs: PACTR201907754270299
Status last verified: Oct 2021
First submitted: 22 Mar 2019
Last updated: 20 Apr 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

Adigweme I, Futa A, Saidy-Jah E, Edem B, Akpalu E, Dibbasey T, Sethna V, Dhere R, Kampmann B, Bengt C, Sirr J, Hosken N, Goldblatt D, Antony K, Alderson MR, Lamola S, Clarke E. Immunogenicity and safety of a 10-valent pneumococcal conjugate vaccine administered as a 2 + 1 schedule to healthy infants in The Gambia: a single-centre, double-blind, active-controlled, randomised, phase 3 trial. Lancet Infect Dis. 2023 May;23(5):609-620. doi: 10.1016/S1473-3099(22)00734-4. Epub 2023 Jan 10.
PubMed 36638819

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Pneumonia, Pneumococcal trials

Study at a glance

From the registry record, last updated by the sponsor on 20 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 3, Randomized, Observer-Blind Study to Evaluate the Safety, Tolerability, Immunogenicity of Serum Institute of India's 10-Valent Pneumococcal Conjugate Vaccine (PNEUMOSIL®) Administered in a 2+1 Schedule to Healthy Infants in The Gambia
ClinicalTrials.gov ID: NCT03896477
Acronym / sponsor ID: CVIA-074
Conditions: Pneumonia, Pneumococcal
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 660 participants (actual)
Lead sponsor: PATHUniversity, hospital or other
Collaborators: Serum Institute of India Pvt. Ltd., Medical Research Council Unit, The Gambia, University College, London, FHI 360
Study start: 18 Jul 2019 (actual)
Primary completion: 17 Dec 2020 (actual)
Study completion: 17 Dec 2020 (actual)
First posted: 1 Apr 2019 (actual)
Results: Posted 20 Apr 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Age 6 weeks: First primary vaccination dose administered
Age 14 weeks: Second primary vaccination dose administered (8 weeks after first primary dose)
Age 18 weeks: Blood sample for immunogenicity testing (4 weeks after second primary dose)
Age 9-18 months: Blood sample for immunogenicity testing and booster vaccination dose administered
Age 10-19 months: Blood sample for immunogenicity testing (4 weeks after booster dose)

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
Pneumosil	Experimental	Biological: PneumosilInfants received two primary vaccinations with Pneumosil, the first at age 6 weeks and the second at age 14 weeks. A booster vaccination was given between 9 and 16 months of age.
Synflorix	Active comparator	Biological: SynflorixInfants received two primary vaccinations with Synflorix, the first at age 6 weeks and the second at age 14 weeks. A booster vaccination was given between 9 and 16 months of age.
Prevenar 13	Active comparator	Biological: Prevenar 13Infants received two primary vaccinations with Prevenar 13, the first at age 6 weeks and the second at age 14 weeks. A booster vaccination was given between 9 and 16 months of age.

Who may qualify

Ages: 42 to 56 days
Sex: All
Healthy volunteers: Accepted
Age groups: Child

Key inclusion criteria (5 listed)

Healthy infants based on medical history and clinical assessment.
Between 6 and 8 weeks (ie 42 to 56 days) old, inclusive.
Subject's parent must provide voluntary written/thumb-printed informed consent and be willing to comply with study requirements and procedures.
Subjects must have been born full-term, have a weight-to-height Z score of ≥ -2 at the time of enrollment (WHO child growth standard), and be ≥ 3.5 kg at randomization.
Subject's parents must be available for the duration of trial participation

Key exclusion criteria (9 listed)

Use of any investigational medicinal product prior to randomization.
Previous vaccination against or infection with S. pneumoniae.
History of anaphylactic shock or an allergic reaction to any prior vaccination.
Any fever, illness (including malaria).
Receipt of another study vaccine within 30 days of study start.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PneumosilAlso: Serum Institute of India Pneumococcal conjugate vaccine (SIIPL-PCV )One single dose contains 2 μg of polysaccharide for serotypes 1, 5, 6A, 7F, 9V, 14, 19A, 19F and 23F, and 4 μg for serotype 6B formulated with aluminium phosphate as an adjuvant in an appropriate buffer	Biological	Pneumosil
Prevenar 13One single dose contains 2.2 µg of the following pneumococcal polysaccharides serotypes - 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F - and 4.4 µg of pneumococcal polysaccharide serotype 6B, all conjugated to CRM197 and absorbed onto aluminum phosphate	Biological	Prevenar 13
SynflorixAlso: Pneumococcal polysaccharide conjugate vaccine (adsorbed)One single dose contains 1 μg of polysaccharide for serotypes 1, 5, 6B, 7F, 9V, 14, and 23F, and 3μg of serotypes 4, 18C, and 19F formulated with aluminum phosphate as an adjuvant.	Biological	Synflorix

Primary outcome

Geometric Mean Concentration (GMC) of Serotype-specific Immunoglobulin G (IgG) Antibodies Four Weeks Post-Booster
Time frame: 4 weeks post booster dose
The IgG antibody concentration to each of the 10 serotypes contained in Pneumosil was measured by enzyme-linked immunosorbent assay (ELISA) in serum samples collected 4 weeks after the booster dose (Visit 6). The pneumococcal serotype-specific IgG ELISAs were performed using the World Health Organisation (WHO) reference assay at the WHO Pneumococcal Serology Reference Laboratory, at the Institute of Child Health, University College London, United Kingdom (UK), where the assay was validated.
Number of Participants With Solicited Local and Systemic Adverse Events (AEs) Through Day 6 Following Any Vaccination
Time frame: Day 0 to Day 6 after each vaccination
Solicited local reactions included tenderness, erythema/redness and induration/swelling at the study vaccine injection site. Solicited systemic reactions included cutaneous rash, fever (based on axillary temperature), irritability, drowsiness, and decreased appetite. The severity of all solicited AEs was graded from mild (Grade 1) to potentially life threatening (Grade 4), based on protocol-defined criteria that were derived from Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (Version 2.0, November 2014).
Number of Participants With Unsolicited Treatment-emergent Adverse Events (TEAEs)
Time frame: AEs were collected from first dose at age 6 weeks up to 9 months of age, and then from the date of the booster vaccination through 4 weeks post vaccination; approximately 8.5 months overall.
AEs include any intercurrent illness or injury during the study, clinically significant worsening of a preexisting condition, and any solicited AE that occurred or was ongoing 6 days after study vaccine administration. A TEAE is an event that was not present prior to administration of the study vaccine, or increased in intensity after administration of the study vaccine. Unsolicited AEs were graded using the scale below: Grade 1: Mild; asymptomatic or mild symptoms; intervention not indicated. Grade 2: Moderate; minimal, local, or noninvasive intervention indicated. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE. Related AEs are AEs where the Investigator determined a reasonable causal relationship between the vaccine administered and the AE based on medical judgement.
Number of Participants With Serious Adverse Events (SAEs)
Time frame: SAEs were collected from first dose at age 6 weeks up to 4 weeks post booster vaccination, approximately 15.5 months overall.
An SAE was a specific AE that: * Resulted in death. * Was life-threatening. * Required inpatient hospitalization or prolongation of an existing hospitalization. * Resulted in a persistent or significant disability or incapacity. * Resulted in a congenital anomaly or birth defect

14 secondary outcomes

Geometric Mean Titers (GMT) of Serotype-specific Opsonophagocytic Activity (OPA) Four Weeks Post-Booster
Time frame: 4 weeks post booster dose
Percentage of Participants With Serotype-specific Serum IgG Antibody Concentrations ≥ 0.35 μg/mL Four Weeks Post-Booster
Time frame: 4 weeks post booster dose
Percentage of Participants With Serotype-specific Serum IgG Antibody Concentrations ≥ 1.0 μg/mL Four Weeks Post-Booster
Time frame: 4 weeks post booster dose
Percentage of Participants With Serotype-specific Serum OPA Titers ≥ 8 Four Weeks Post-Booster
Time frame: 4 weeks post booster dose
Percentage of Participants With Serotype-specific Serum IgG Antibody Concentrations ≥ 0.35 μg/mL Four Weeks After Completion of Primary Vaccinations
Time frame: 4 weeks after completion of primary vaccinations (at age 18 weeks)
Geometric Mean Concentration of Serotype-specific IgG Antibodies Four Weeks After Completion of Primary Vaccinations
Time frame: 4 weeks after completion of primary vaccinations (at age 18 weeks)
Percentage of Participants With Serotype-specific Serum OPA Titers ≥ 8 Four Weeks After Completion of Primary Vaccinations
Time frame: 4 weeks after completion of primary vaccinations (at age 18 weeks)
Geometric Mean Titers of Serotype-specific Serum OPA Four Weeks After Primary Vaccinations
Time frame: 4 weeks after completion of primary vaccinations (at age 18 weeks)
Percentage of Participants With Serotype-specific Serum IgG Concentrations ≥ 0.35 μg/mL Prior to Booster
Time frame: Prior to the booster dose at approximately 9 to 16 months of age
Geometric Mean Concentration of Serotype-specific Serum IgG Antibodies Prior to Booster
Time frame: Prior to the booster dose at approximately 9 to 16 months of age
Percentage of Participants With Serotype-specific Serum OPA Titers ≥ 8 Prior to Booster
Time frame: Prior to the booster dose at approximately 9 to 16 months of age
Geometric Mean Titer of Serotype-specific Serum OPA Prior to Booster
Time frame: Prior to the booster dose at approximately 9 to 16 months of age
Ratio of Serotype-specific Serum IgG GMC 4 Weeks Post-Booster to Serotype-specific IgG GMC 4 Weeks After Completion of Primary Vaccinations
Time frame: 4 weeks after completion of primary vaccinations (at age 18 weeks) and 4 weeks post booster
Ratio of Serotype-specific Serum OPA GMT 4 Weeks Post-Booster to Serotype-specific OPA GMT 4 Weeks After Completion of Primary Vaccinations
Time frame: 4 weeks after completion of primary vaccinations (at age 18 weeks) and 4 weeks post booster

Results and safety

Results posted to the registry on 20 Apr 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Pneumosil	220	203
Synflorix	220	200
Prevenar 13	220	200

Primary outcome: Geometric Mean Concentration (GMC) of Serotype-specific Immunoglobulin G (IgG) Antibodies Four Weeks Post-Booster

Time frame: 4 weeks post booster dose. Geometric mean (95% Confidence Interval). Unit: μg/mL

Measure	Pneumosil n = 202	Synflorix n = 200	Prevenar 13 n = 200
Serotype 1	8.45 (7.54 to 9.48)	2.90 (2.57 to 3.28)	5.87 (5.26 to 6.56)
Serotype 5	1.54 (1.38 to 1.73)	0.80 (0.72 to 0.88)	2.04 (1.86 to 2.24)
Serotype 6A	9.56 (8.26 to 11.05)	0.60 (0.50 to 0.71)	10.95 (9.57 to 12.54)
Serotype 6B	12.46 (11.07 to 14.01)	4.96 (4.44 to 5.53)	15.54 (13.71 to 17.60)
Serotype 7F	6.66 (5.96 to 7.44)	3.15 (2.87 to 3.45)	6.31 (5.75 to 6.93)
Serotype 9V	3.46 (3.08 to 3.88)	2.45 (2.21 to 2.72)	3.87 (3.47 to 4.32)
Serotype 14	8.28 (6.97 to 9.82)	5.02 (4.22 to 5.97)	9.17 (8.06 to 10.45)
Serotype 19A	8.82 (7.65 to 10.15)	2.39 (1.97 to 2.89)	12.21 (10.83 to 13.76)

Pneumosil vs Synflorix: GMC Ratio: 2.91 (95% CI 2.47 to 3.44)
Pneumosil vs Prevenar 13: GMC Ratio: 1.44 (95% CI 1.23 to 1.69)
Pneumosil vs Synflorix: GMC Ratio: 1.93 (95% CI 1.66 to 2.25)

Population analysed: Primary Per Protocol Immunogenicity Population (PP\_IMM) includes all randomized participants who received all 3 study vaccinations (including booster), contributed post-booster immunogenicity measurements, and with no major protocol deviations that were determined to potentially interfere with immunogenicity assessment. Participants with available data for each serotype are included in the analysis.

Primary outcome: Number of Participants With Solicited Local and Systemic Adverse Events (AEs) Through Day 6 Following Any Vaccination

Time frame: Day 0 to Day 6 after each vaccination. Count of participants. Unit: Participants

Measure	Pneumosil n = 220	Synflorix n = 220	Prevenar 13 n = 220
Any local reaction	72	84	63
Any local reaction Grade 3 or higher	0	0	0
Tenderness	70	83	61
Erythema/Redness	1	3	1
Induration/Swelling	3	5	1
Any systemic reaction	160	167	160
Any systemic reaction Grade 3 or higher	3	0	2
Fever	98	105	108

Population analysed: The Safety Analysis Set (Safety Population) included all participants who were randomized, received a study vaccination, and provided post-vaccination safety data.

Primary outcome: Number of Participants With Unsolicited Treatment-emergent Adverse Events (TEAEs)

Time frame: AEs were collected from first dose at age 6 weeks up to 9 months of age, and then from the date of the booster vaccination through 4 weeks post vaccination; approximately 8.5 months overall.. Count of participants. Unit: Participants

Measure	Pneumosil n = 220	Synflorix n = 220	Prevenar 13 n = 220
Any treatment-emergent adverse event (TEAE)	198	197	189
Any vaccine-related TEAE	1	2	0
Grade 1 TEAE	196	195	186
Vaccine-related Grade 1 TEAE	1	1	0
Grade 2 TEAE	22	20	17
Vaccine-related Grade 2 TEAE	0	0	0
Grade 3 TEAE	11	10	6
Vaccine-related Grade 3 TEAE	0	1	0

Population analysed: Safety analysis set

Primary outcome: Number of Participants With Serious Adverse Events (SAEs)

Time frame: SAEs were collected from first dose at age 6 weeks up to 4 weeks post booster vaccination, approximately 15.5 months overall.. Count of participants. Unit: Participants

Measure	Pneumosil n = 220	Synflorix n = 220	Prevenar 13 n = 220
Any serious adverse event	12	10	7
Vaccine-related serious adverse events	0	0	0

Population analysed: Safety analysis set

14 secondary outcomes are reported in the full results.

Adverse events

Time frame: All-cause mortality and SAEs were collected from first dose at age 6 weeks up to 4 weeks post booster vaccination, approximately 15.5 months overall. Non-serious AEs were collected from first dose at age 6 weeks up to 9 months of age, and then from the date of the booster vaccination through 4 weeks post booster vaccination; approximately 8.5 months overall.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Pneumosil	12 of 220 (5.5%)	212 of 220 (96.4%)	1 of 220
Synflorix	10 of 220 (4.5%)	213 of 220 (96.8%)	0 of 220
Prevenar 13	7 of 220 (3.2%)	211 of 220 (95.9%)	1 of 220

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 36638819Adigweme I, Futa A, Saidy-Jah E, Edem B, Akpalu E, Dibbasey T, Sethna V, Dhere R, Kampmann B, Bengt C, Sirr J, Hosken N, Goldblatt D, Antony K, Alderson MR, Lamola S, Clarke E. Immunogenicity and safety of a 10-valent pneumococcal conjugate vaccine administered as a 2 + 1 schedule to healthy infants in The Gambia: a single-centre, double-blind, active-controlled, randomised, phase 3 trial. Lancet Infect Dis. 2023 May;23(5):609-620. doi: 10.1016/S1473-3099(22)00734-4. Epub 2023 Jan 10.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Ed Clarke, MB ChB, PhD principal investigator

MRCG at LSHTM

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Pneumosil, Prevenar 13 and Synflorix in people with Pneumonia, Pneumococcal, run by PATH at 1 site in The Gambia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in The Gambia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Apr 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Geometric Mean Concentration (GMC) of Serotype-specific Immunoglobulin G (IgG) Antibodies Four Weeks Post-Booster (time frame: 4 weeks post booster dose). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03896477, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Apr 2022.