Pneumonia, PneumococcalPhase 3NCT03197376

Phase 3 Study of 10-valent Pneumococcal Conjugate Vaccine (PNEUMOSIL) in Healthy Infants

A Phase 3 study testing Pneumosil 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

Search all trials

Trial summary

This study will examine the consistency of 3 batches of the Pneumosil vaccine by looking at the immune response in infants. In addition, the study will compare the immunogenicity of the Pneumosil vaccine to another WHO-prequalified vaccine, Synflorix. Read more about this study

Who is it for?: Ages 6 to 8 weeksHealthy volunteers can take part
Conditions the study is for: Pneumonia, Pneumococcal
What is being tested?: Pneumosil and Synflorix
Type of treatment: Vaccines
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 2,250 participants
Where: 1 siteThe Gambia
Study dates: 21 Jun 2017to 9 May 2019
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 6 to 8 weeks
All sexes
Healthy volunteers accepted
Child

Who may be able to join

They are healthy infants based on medical history and clinical assessment.
They are 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.

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 vaccine within 30 days of study start.
Chronic administration of an immunosuppressant or administration of immunoglobulins
History of blood disorder, primary immunodeficiency, or a sibling who has such a diagnosis or who died of suddenly without apparent cause.
History of meningitis, seizures or any neurological disorder.

Trial locations and contacts

1 site in 1 country.

The Gambia1 site

Medical Research Council (MRC) Unit, The Gambia
Fajara

Other trials in The Gambia

About this study

Official title: A Phase 3, Randomized, Double-Blind Study of the Safety, Tolerability, Lot-to-Lot Consistency, Immunogenicity & Non-Interference With Concomitant Vaccinations of Serum Institute of PNEUMOSIL in Healthy Infants in The Gambia

Read the detailed description

This is a randomized, active-controlled, double-blind, Phase 3 study in 2,250 healthy infants (6 to 8 weeks of age). Subjects will receive 3 doses of either PNEUMOSIL (3 groups receiving vaccine from different lots) or Synflorix (1 group) at 6, 10, and 14 weeks of age. The first 675 randomized subjects will receive a booster dose of either PNEUMOSIL or Synflorix at 9 months of age that matches the treatment assignment for the priming phase. Standard EPI vaccinations in The Gambia will be given concomitantly with all 4 doses of the study vaccines. Out of the 675 booster subjects, subjects who consented for further evaluation will participate for the assessment of immune persistence 12 (+1) months after the booster vaccination

The primary objectives are to demonstrate that the three lots of the Pneumosil vaccine is consistent by evaluating the immune responses, and to demonstrate that the immune responses generated by Pneumosil are non-inferior to those generated by Synflorix. The safety and tolerability of Pneumosil will also be evaluated.

Conditions: Pneumonia, Pneumococcal
Being tested: Pneumosil, 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
10-Valent Pneumococcal Conjugate Vaccine
SynflorixBiological
Pneumococcal conjugate vaccine (Non-Typeable Haemophilus influenzae (NTHi) protein D, diphtheria or tetanus toxoid conjugates) adsorbed

Study groups in NCT03197376
Study group	Role	What they receive
Pneumosil Lot 1	Experimental	Pneumosil Lot 1 Receives: Biological: Pneumosil
Pneumosil Lot 2	Experimental	Pneumosil Lot 2 Receives: Biological: Pneumosil
Pneumosil Lot 3	Experimental	Pneumosil Lot 3 Receives: Biological: Pneumosil
Synflorix	Active comparator	Synflorix Receives: Biological: Synflorix

What is being measured

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

Serotype-specific Geometric Mean Concentration of IgG Antibody
Serotype-specific concentrations of immunoglobulin G (IgG) antibody measured by ELISA
Measured: 4 weeks after the third dose
Number and Percentage of Subjects With Serotype-specific IgG Antibody Responses ≥ 0.35 μg/mL
Number and Percentage of subjects with serotype-specific IgG Antibody Responses ≥ 0.35 μg/mL
Measured: 4 weeks after the third dose
Serotype-specific Geometric Mean Concentration of IgG Antibody
Serotype-specific immunoglobulin G (IgG) geometric mean concentration (GMC) 4 weeks after the primary series of PNEUMOSIL/Synflorix co-administered with pentavalent, RV and polio vaccines.
Measured: 4 weeks after the third dose
Number and Percentage of Subjects With EPI Vaccine Immune Responses (Diphtheria, Tetanus, Hepatitis B, Hib, Polio and Rotavirus)
Subjects with 1) anti-diphtheria toxoid (DT) and anti-tetanus toxoid (DT) IgG concentration ≥ 0.1 IU/mL; 2) anti-Hepatitis B surface antigen (HBsAg) IgG concentration ≥ 10 mIU/mL; 3) anti-Hib (polyribosylribitol phosphate [PRP]) IgG concentration ≥ 0.15 µg/mL; 4) anti-poliovirus types 1, 2 and 3 neutralizing antibody titers ≥ 1:8; 5) anti-rotavirus IgA concentration ≥ 20 U/mL.
Measured: 4 weeks after the third dose
Anti-pertussis Toxoid GMCs for the Pertussis Antigen
Anti-pertussis toxoid GMCs for the pertussis antigen
Measured: 4 weeks after the third dose
Anti Fimbriae 2/3 IgG GMCs for the Pertussis Antigen
Anti fimbriae 2/3 IgG GMCs for the pertussis antigen
Measured: 4 weeks after the third dose
Number and Percentage of Solicited Local and Systemic Reactogenicity by Severity- Vaccination 1
In the primary reactogenicity cohort, local and systemic reactogenicity of the study vaccine was evaluated through day 6 for severity by toxicity grading scale (0 [none], 1 [mild], 2 [moderate], 3 [severe], 4 [life threatening].
Measured: 7 days (including day of vaccination)
Number and Percentage of Solicited Local and Systemic Reactogenicity by Severity- Vaccination 2
In the primary reactogenicity cohort, local and systemic reactogenicity of the study vaccine was evaluated through day 6 for severity by toxicity grading scale (0 [none], 1 [mild], 2 [moderate], 3 [severe], 4 [life threatening].
Measured: 7 days (including day of vaccination)
Number and Percentage of Solicited Local and Systemic Reactogenicity by Severity- Vaccination 3
In the primary reactogenicity cohort, local and systemic reactogenicity of the study vaccine was evaluated through day 6 for severity by toxicity grading scale (0 [none], 1 [mild], 2 [moderate], 3 [severe], 4 [life threatening].
Measured: 7 days (including day of vaccination)
Number and Percentage of Solicited Local and Systemic Reactogenicity by Severity- Booster
In the primary reactogenicity cohort, local and systemic reactogenicity of the study vaccine was evaluated through day 6 for severity by toxicity grading scale (0 [none], 1 [mild], 2 [moderate], 3 [severe], 4 [life threatening].
Measured: 7 days (including day of vaccination)
Number and Percentage of All AEs Including SAEs Occurring in Greater Than 1% Subjects by Severity and Relatedness
All subjects were followed up for AEs till 4 weeks post vaccination dose 3 and subjects in the booster cohort were followed up for AEs till 4 weeks post booster vaccination
Measured: 4 weeks post last vaccination
Number and Percentage of All SAEs by Severity and Relatedness
All subjects were followed up for SAEs till 4 weeks post vaccination dose 3 and subjects in the booster cohort were followed up for SAEs till 4 weeks post booster vaccination
Measured: 4 weeks post last vaccination

Secondary outcomes (9)

Number and Percentage of Subjects With 6A and 19A Serotype-specific Concentrations of Immunoglobulin G Antibody
Subjects with 6A and 19A serotype-specific concentrations of immunoglobulin G (IgG) antibody measured by ELISA
Measured: 4 weeks after the third dose
6A and 19A Serotype Specific Geometric Mean Concentration of IgG Antibody
6A and 19A Serotype Specific Immune Responses in terms of IgG GMCs measured by ELISA
Measured: 4 weeks after the third dose
Number and Percentage of Subjects With Functional Antibody Responses
Serotype-specific functional antibody titer measured by OPA
Measured: 4 weeks after the third dose
Serotype-specific OPA Geometric Mean Titer
Serotype-specific functional antibody titer measured by OPA and expressed as OPA GMT in a subset
Measured: 4 weeks after the third dose
Comparison of Serotype-specific Geometric Mean Concentration of IgG Antibody Response 4 Weeks After a 3-dose Primary Series to 4 Weeks After a Booster Dose
Comparison of Serotype-specific booster responses (antibody concentrations) measured by ELISA from 4 weeks after a 3-dose primary series to 4 weeks after a booster dose
Measured: 4 weeks post booster vaccination
Serotype-specific Geometric Mean Concentration of IgG Antibody Response and Treatment-Group GMC Ratios 4 Weeks After a Booster Dose
Comparison of Serotype-specific booster responses (antibody concentrations) to PNEUMOSIL in comparison to Synflorix 4 weeks after a booster dose
Measured: 4 weeks post booster vaccination
Comparison of Functional Response (OPA) From 4 Weeks After a 3-dose Primary Series to 4 Weeks After a Booster Dose
Comparison of Serotype-specific booster responses (functional response-OPA) from 4 weeks after a 3-dose primary series to 4 weeks after a booster dose
Measured: 4 weeks post booster vaccination
Serotype-specific OPA GMT and Treatment-Group GMT Ratios 4 Weeks After a Booster Dose
Comparison of Serotype-specific booster responses (functional response) to PNEUMOSIL in comparison to Synflorix 4 weeks after a booster dose
Measured: 4 weeks post booster vaccination
Number and Percentage of Subjects With EPI Vaccine Immune Responses (Measles, Rubella and Yellow Fever)
Anti-measles IgG, anti-rubella IgG and anti-yellow fever neutralizing antibody titer
Measured: 4 weeks post booster vaccination

Timeline

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

21 Jun 20179 May 2019

First posted23 Jun 2017
Study start21 Jun 2017
Primary completion6 Jun 2018
Study completion9 May 2019

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: 2,250 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03197376
Sponsor's protocol ID: VAC-056
Status last verified: Aug 2019
First submitted: 21 Jun 2017
Last updated: 14 Jul 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No

Publications

Clarke E, Bashorun A, Adigweme I, Badjie Hydara M, Umesi A, Futa A, Ochoge M, Obayemi D, Edem B, Saidy-Jah E, Onwuchekwa C, Dhere R, Sethna V, Kampmann B, Goldblatt D, Taylor D, Andi-Lolo I, Hosken N, Antony K, Innis BL, Alderson MR, Lamola S. Immunogenicity and safety of a novel ten-valent pneumococcal conjugate vaccine in healthy infants in The Gambia: a phase 3, randomised, double-blind, non-inferiority trial. Lancet Infect Dis. 2021 Jun;21(6):834-846. doi: 10.1016/S1473-3099(20)30735-0. Epub 2021 Jan 28.
PubMed 33516293

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

Active, not recruitingPhase 3
A Clinical Study to Evaluate the Safety, Tolerability, and Immunogenicity of VAX-31 With Influenza Vaccine in Adults ≥ 50 Years of Age
Pneumococcal Disease
Active, not recruitingPhase 1
Trial to Evaluate Safety and Immune Response of an Investigational Pneumococcal Vaccine in Adults Aged 50 To 64 Years
Pneumonia, Bacterial
Active, not recruitingObservational study
A Study to Learn How Effective is PCV20 to Help Stop Adults Who Have a Higher Chance of Getting Pneumonia
Community-Acquired Pneumonia (CAP)
RecruitingObservational study
Pneumonia and Pleuropneumonia in Hospitalized Children
Pneumonia, Pleural Effusion
RecruitingPhase 4
Opportunistic Pneumococcal Immunisation Trial in MALnutrition
Severe Acute Malnutrition in Childhood, Pneumococcal Disease

All Pneumonia, Pneumococcal trials

Study at a glance

From the registry record, last updated by the sponsor on 14 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 3, Randomized, Double-Blind Study of the Safety, Tolerability, Lot-to-Lot Consistency, Immunogenicity & Non-Interference With Concomitant Vaccinations of Serum Institute of PNEUMOSIL in Healthy Infants in The Gambia
ClinicalTrials.gov ID: NCT03197376
Acronym / sponsor ID: VAC-056
Conditions: Pneumonia, Pneumococcal
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 2,250 participants (actual)
Lead sponsor: PATHUniversity, hospital or other
Study start: 21 Jun 2017 (actual)
Primary completion: 6 Jun 2018 (actual)
Study completion: 9 May 2019 (actual)
First posted: 23 Jun 2017 (actual)
Results: Posted 11 Sep 2019

Clinical summary

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

Detailed description

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 4

Arm	Type	Receives
Pneumosil Lot 1	Experimental	Biological: PneumosilPneumosil Lot 1
Pneumosil Lot 2	Experimental	Biological: PneumosilPneumosil Lot 2
Pneumosil Lot 3	Experimental	Biological: PneumosilPneumosil Lot 3
Synflorix	Active comparator	Biological: SynflorixSynflorix

Who may qualify

Ages: 6 to 8 weeks
Sex: All
Healthy volunteers: Accepted
Age groups: Child

Key inclusion criteria (3 listed)

They are healthy infants based on medical history and clinical assessment.
They are 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.

Key exclusion criteria (8 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 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
Pneumosil10-Valent Pneumococcal Conjugate Vaccine	Biological	Pneumosil Lot 1, Pneumosil Lot 2, Pneumosil Lot 3
SynflorixPneumococcal conjugate vaccine (Non-Typeable Haemophilus influenzae (NTHi) protein D, diphtheria or tetanus toxoid conjugates) adsorbed	Biological	Synflorix

Primary outcome

Serotype-specific Geometric Mean Concentration of IgG Antibody
Time frame: 4 weeks after the third dose
Serotype-specific concentrations of immunoglobulin G (IgG) antibody measured by ELISA
Number and Percentage of Subjects With Serotype-specific IgG Antibody Responses ≥ 0.35 μg/mL
Time frame: 4 weeks after the third dose
Number and Percentage of subjects with serotype-specific IgG Antibody Responses ≥ 0.35 μg/mL
Serotype-specific Geometric Mean Concentration of IgG Antibody
Time frame: 4 weeks after the third dose
Serotype-specific immunoglobulin G (IgG) geometric mean concentration (GMC) 4 weeks after the primary series of PNEUMOSIL/Synflorix co-administered with pentavalent, RV and polio vaccines.
Number and Percentage of Subjects With EPI Vaccine Immune Responses (Diphtheria, Tetanus, Hepatitis B, Hib, Polio and Rotavirus)
Time frame: 4 weeks after the third dose
Subjects with 1) anti-diphtheria toxoid (DT) and anti-tetanus toxoid (DT) IgG concentration ≥ 0.1 IU/mL; 2) anti-Hepatitis B surface antigen (HBsAg) IgG concentration ≥ 10 mIU/mL; 3) anti-Hib (polyribosylribitol phosphate [PRP]) IgG concentration ≥ 0.15 µg/mL; 4) anti-poliovirus types 1, 2 and 3 neutralizing antibody titers ≥ 1:8; 5) anti-rotavirus IgA concentration ≥ 20 U/mL.
Anti-pertussis Toxoid GMCs for the Pertussis Antigen
Time frame: 4 weeks after the third dose
Anti-pertussis toxoid GMCs for the pertussis antigen
Anti Fimbriae 2/3 IgG GMCs for the Pertussis Antigen
Time frame: 4 weeks after the third dose
Anti fimbriae 2/3 IgG GMCs for the pertussis antigen
Number and Percentage of Solicited Local and Systemic Reactogenicity by Severity- Vaccination 1
Time frame: 7 days (including day of vaccination)
In the primary reactogenicity cohort, local and systemic reactogenicity of the study vaccine was evaluated through day 6 for severity by toxicity grading scale (0 [none], 1 [mild], 2 [moderate], 3 [severe], 4 [life threatening].
Number and Percentage of Solicited Local and Systemic Reactogenicity by Severity- Vaccination 2
Time frame: 7 days (including day of vaccination)
In the primary reactogenicity cohort, local and systemic reactogenicity of the study vaccine was evaluated through day 6 for severity by toxicity grading scale (0 [none], 1 [mild], 2 [moderate], 3 [severe], 4 [life threatening].
Number and Percentage of Solicited Local and Systemic Reactogenicity by Severity- Vaccination 3
Time frame: 7 days (including day of vaccination)
In the primary reactogenicity cohort, local and systemic reactogenicity of the study vaccine was evaluated through day 6 for severity by toxicity grading scale (0 [none], 1 [mild], 2 [moderate], 3 [severe], 4 [life threatening].
Number and Percentage of Solicited Local and Systemic Reactogenicity by Severity- Booster
Time frame: 7 days (including day of vaccination)
In the primary reactogenicity cohort, local and systemic reactogenicity of the study vaccine was evaluated through day 6 for severity by toxicity grading scale (0 [none], 1 [mild], 2 [moderate], 3 [severe], 4 [life threatening].
Number and Percentage of All AEs Including SAEs Occurring in Greater Than 1% Subjects by Severity and Relatedness
Time frame: 4 weeks post last vaccination
All subjects were followed up for AEs till 4 weeks post vaccination dose 3 and subjects in the booster cohort were followed up for AEs till 4 weeks post booster vaccination
Number and Percentage of All SAEs by Severity and Relatedness
Time frame: 4 weeks post last vaccination
All subjects were followed up for SAEs till 4 weeks post vaccination dose 3 and subjects in the booster cohort were followed up for SAEs till 4 weeks post booster vaccination

9 secondary outcomes

Number and Percentage of Subjects With 6A and 19A Serotype-specific Concentrations of Immunoglobulin G Antibody
Time frame: 4 weeks after the third dose
6A and 19A Serotype Specific Geometric Mean Concentration of IgG Antibody
Time frame: 4 weeks after the third dose
Number and Percentage of Subjects With Functional Antibody Responses
Time frame: 4 weeks after the third dose
Serotype-specific OPA Geometric Mean Titer
Time frame: 4 weeks after the third dose
Comparison of Serotype-specific Geometric Mean Concentration of IgG Antibody Response 4 Weeks After a 3-dose Primary Series to 4 Weeks After a Booster Dose
Time frame: 4 weeks post booster vaccination
Serotype-specific Geometric Mean Concentration of IgG Antibody Response and Treatment-Group GMC Ratios 4 Weeks After a Booster Dose
Time frame: 4 weeks post booster vaccination
Comparison of Functional Response (OPA) From 4 Weeks After a 3-dose Primary Series to 4 Weeks After a Booster Dose
Time frame: 4 weeks post booster vaccination
Serotype-specific OPA GMT and Treatment-Group GMT Ratios 4 Weeks After a Booster Dose
Time frame: 4 weeks post booster vaccination
Number and Percentage of Subjects With EPI Vaccine Immune Responses (Measles, Rubella and Yellow Fever)
Time frame: 4 weeks post booster vaccination

Results and safety

Results posted to the registry on 11 Sep 2019, 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 Lot 1	502	487
Pneumosil Lot 2	501	488
Pneumosil Lot 3	500	480
Synflorix	747	722

Primary outcome: Serotype-specific Geometric Mean Concentration of IgG Antibody

Time frame: 4 weeks after the third dose. Geometric mean (95% Confidence Interval). Unit: µg/mL

Measure	Lot 1 n = 487	Lot 2 n = 490	Lot 3 n = 481
Pn IgG Type 1	4.08 (3.84 to 4.33)	4.24 (3.97 to 4.52)	4.58 (4.30 to 4.87)
Pn IgG Type 5	1.34 (1.27 to 1.43)	1.80 (1.70 to 1.91)	1.84 (1.73 to 1.96)
Pn IgG Type 6A	1.05 (0.95 to 1.15)	0.95 (0.86 to 1.06)	1.01 (0.91 to 1.11)
Pn IgG Type 6B	1.30 (1.15 to 1.47)	0.92 (0.81 to 1.05)	1.49 (1.32 to 1.68)
Pn IgG Type 7F	2.79 (2.61 to 2.98)	2.55 (2.37 to 2.75)	3.70 (3.46 to 3.96)
Pn IgG Type 9V	1.28 (1.20 to 1.37)	1.19 (1.11 to 1.28)	1.46 (1.36 to 1.56)
Pn IgG Type 14	4.99 (4.52 to 5.51)	5.37 (4.87 to 5.92)	5.25 (4.78 to 5.76)
Pn IgG Type 19A	1.53 (1.42 to 1.66)	1.66 (1.53 to 1.79)	1.74 (1.61 to 1.88)

Lot 1 vs Lot 2: Pn IgG type 1 GMC Ratio: 0.96 (95% CI 0.88 to 1.05)
Lot 1 vs Lot 2: Pn IgG type 5 GMC Ratio: 0.75 (95% CI 0.69 to 0.81)
Lot 1 vs Lot 2: Pn IgG type 6A GMC Ratio: 1.1 (95% CI 0.96 to 1.26)

Population analysed: All subjects who received all primary series doses of study vaccines, had post-dose immunogenicity measurement(s) with no major protocol deviations

Primary outcome: Number and Percentage of Subjects With Serotype-specific IgG Antibody Responses ≥ 0.35 μg/mL

Time frame: 4 weeks after the third dose. Count of participants. Unit: Participants

Measure	Pneumosil n = 1458	Synflorix n = 724
Pn IgG Type 1	1454	717
Pn IgG Type 5	1435	692
Pn IgG Type 6A	1193	555
Pn IgG Type 6B	1142	555
Pn IgG Type 7F	1443	709
Pn IgG Type 9V	1391	690
Pn IgG Type 14	1437	715
Pn IgG Type 19A	1386	555

Pneumosil vs Synflorix: Absolute Difference for Type 1: 0.7 (97.5% CI -0.0 to 1.9)
Pneumosil vs Synflorix: Absolute Difference for Type 5: 2.8 (97.5% CI 1.2 to 5.0)
Pneumosil vs Synflorix: Absolute Difference for Type 6A: 5.2 (97.5% CI 1.1 to 9.5)

Population analysed: Non-inferiority for each serotype is based on 2 non-inferiority criteria evaluation: for each serotype, non-inferiority was shown if a two-sided 97.5% CI for the absolute difference in proportions responding (PNEUMOSIL-Synflorix) had a lower limit \>-0.10, or if a two-sided 97.5% CI for the IgG GMC ratio (PNEUMOSIL/Synflorix) had a lower limit \>0.5.

Primary outcome: Serotype-specific Geometric Mean Concentration of IgG Antibody

Time frame: 4 weeks after the third dose. Geometric mean (95% Confidence Interval). Unit: µg/mL

Measure	Pneumosil n = 1458	Synflorix n = 724
Pn IgG Type 1	4.29 (4.14 to 4.45)	1.99 (1.88 to 2.11)
Pn IgG Type 5	1.65 (1.59 to 1.71)	1.20 (1.14 to 1.26)
Pn IgG Type 6A	1.00 (0.95 to 1.06)	1.13 (1.02 to 1.25)
Pn IgG Type 6B	1.21 (1.13 to 1.30)	1.13 (1.02 to 1.25)
Pn IgG Type 7F	2.97 (2.85 to 3.10)	2.29 (2.16 to 2.43)
Pn IgG Type 9V	1.31 (1.26 to 1.36)	1.42 (1.34 to 1.50)
Pn IgG Type 14	5.20 (4.92 to 5.50)	4.24 (3.90 to 4.61)
Pn IgG Type 19A	1.64 (1.57 to 1.72)	1.13 (1.02 to 1.25)

Pneumosil vs Synflorix: Pn IgG type 1 GMC Ratio: 2.15 (97.5% CI 2.00 to 2.32)
Pneumosil vs Synflorix: Pn IgG type 5 GMC Ratio: 1.37 (97.5% CI 1.28 to 1.47)
Pneumosil vs Synflorix: Pn IgG type 6A GMC Ratio: 0.89 (97.5% CI 0.78 to 1.01)

Primary outcome: Number and Percentage of Subjects With EPI Vaccine Immune Responses (Diphtheria, Tetanus, Hepatitis B, Hib, Polio and Rotavirus)

Time frame: 4 weeks after the third dose. Count of participants. Unit: Participants

Measure	Pneumosil n = 447	Synflorix n = 225
Anti-Diphtheria Toxoid ≥ 0.1 IU/mL	447	225
Anti-Tetanus Toxoid ≥ 0.1 IU/mL	447	225
Anti-HBsAg concentration ≥ 10 mIU/mL	447	224
Anti-PRP concentration ≥ 0.15 μg/mL	441	224
Anti-Polio titer ≥ 1:8 (type 1)	446	225
Anti-Polio titer ≥ 1:8 (type 2)	374	182
Anti-Polio titer ≥ 1:8 (type 3)	437	222
Anti-Rotavirus concentration ≥ 20 U/mL	122	61

Pneumosil vs Synflorix: Absolute difference for diphtheria: 0.0
Pneumosil vs Synflorix: Absolute difference for Tetanus: 0.0
Pneumosil vs Synflorix: Absolute difference for Hepatitis B: 0.4 (95% CI -0.4 to 2.5)

Population analysed: Evaluated in a subset who got 3 primary doses, had postdose immunogenicity data with no major protocol deviations.For each Ag in the pentavalent, RV, OPV vaccines, non-inferiority shown if 2-sided 95% CI for difference in response proportions (PNEUMOSIL-Synflorix) had lower limit \>-0.10. For this, pooled PNUEMOSIL data was used as specified in SAP.

9 secondary outcomes are reported in the full results.

Adverse events

Time frame: Recording and reporting of all AEs occurred from signing of the ICF (6-8 weeks of age) through the EOS visit for each subject enrolled in the priming phase of the study (upto 18-20 weeks of age), and through Visit 6 for each study subject enrolled in the booster phase (upto 12 months of age). Subjects included in the third phase for immune persistence evaluation, serious adverse events were monitored from 4 weeks post booster to 12 months after booster.. Other adverse events reported at 1% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Pneumosil	51 of 1,503 (3.4%)	1,131 of 1,503 (75.2%)	1 of 1,503
Synflorix	26 of 747 (3.5%)	572 of 747 (76.6%)	2 of 747

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 33516293Clarke E, Bashorun A, Adigweme I, Badjie Hydara M, Umesi A, Futa A, Ochoge M, Obayemi D, Edem B, Saidy-Jah E, Onwuchekwa C, Dhere R, Sethna V, Kampmann B, Goldblatt D, Taylor D, Andi-Lolo I, Hosken N, Antony K, Innis BL, Alderson MR, Lamola S. Immunogenicity and safety of a novel ten-valent pneumococcal conjugate vaccine in healthy infants in The Gambia: a phase 3, randomised, double-blind, non-inferiority trial. Lancet Infect Dis. 2021 Jun;21(6):834-846. doi: 10.1016/S1473-3099(20)30735-0. Epub 2021 Jan 28.

Related trials for Pneumonia, Pneumococcal

Active, not recruitingPhase 3
A Clinical Study to Evaluate the Safety, Tolerability, and Immunogenicity of VAX-31 With Influenza Vaccine in Adults ≥ 50 Years of Age
Pneumococcal Disease
Active, not recruitingPhase 1
Trial to Evaluate Safety and Immune Response of an Investigational Pneumococcal Vaccine in Adults Aged 50 To 64 Years
Pneumonia, Bacterial
Active, not recruitingObservational study
A Study to Learn How Effective is PCV20 to Help Stop Adults Who Have a Higher Chance of Getting Pneumonia
Community-Acquired Pneumonia (CAP)
RecruitingObservational study
Pneumonia and Pleuropneumonia in Hospitalized Children
Pneumonia, Pleural Effusion
RecruitingPhase 4
Opportunistic Pneumococcal Immunisation Trial in MALnutrition
Severe Acute Malnutrition in Childhood, Pneumococcal Disease

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 principal investigator

Medical Research Council (MRC) Unit, The Gambia

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 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 3 inclusion and 8 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 14 Jul 2020. 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 11 Sep 2019). 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?

Serotype-specific Geometric Mean Concentration of IgG Antibody (time frame: 4 weeks after the third dose). The study lists 12 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 NCT03197376, 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 14 Jul 2020.