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NCT04384107

Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 in Healthy Japanese Infants (V114-033)

Completed Phase 3 Results posted Last updated 28 July 2023
What this trial tests

Phase 3 trial testing V114 in Pneumococcal Infections in 694 participants. Completed in 1 December 2021.

Timeline
1 July 2020
Primary endpoint
1 December 2021
1 December 2021

Quick facts

Lead sponsorMerck Sharp & Dohme LLC
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingtriple
Primary purposeprevention
Enrollment694
Start date1 July 2020
Primary completion1 December 2021
Estimated completion1 December 2021
Sites45 locations across Japan

Drugs / interventions tested

Conditions studied

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

Adults 2 Months to 6 Months, any sex, with Pneumococcal Infections. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants With Solicited Injection-Site Adverse Events Primary · Day 1 to Day 14 post any vaccination, up to a total of 13.5 months

An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Following any injection with either V114 or PCV13 the percentage of participants with solicited injection-site AEs was assessed. The solicited injection-site AEs were erythema, induration, pain, and swelling.

Injection site erythema
GroupValue95% CI
V11488.2
PCV1389.3
Injection site induration
GroupValue95% CI
V11481.0
PCV1381.2
Injection site pain
GroupValue95% CI
V11431.1
PCV1324.0
Injection site swelling
GroupValue95% CI
V11475.8
PCV1379.8
Percentage of Participants With Solicited Systemic Adverse Events Primary · Day 1 to Day 14 post any vaccination, up to a total of 13.5 months

An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Following any of the injections with either V114 or PCV13, the percentage of participants with solicited systemic AEs was assessed. The solicited systemic AEs assessed were decreased appetite, irritability, somnolence, and urticaria.

Decreased appetite
GroupValue95% CI
V11423.9
PCV1324.3
Irritability
GroupValue95% CI
V11466.6
PCV1360.7
Somnolence
GroupValue95% CI
V11455.9
PCV1354.9
Urticaria
GroupValue95% CI
V1144.0
PCV134.3
Percentage of Participants With Vaccine-Related Serious Adverse Events Primary · ~1 month after Dose 4, up to a total of 14 months

A serious adverse event (SAE) is an AE that is life-threatening, requires or prolongs an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is another important medical event deemed such by medical or scientific judgment. The percentage of participants with a vaccine-related SAE following dose 1 (with either V114 or PCV13) was reported. Vaccine-related SAEs were counted starting after vaccine dose 1 through completion of study.

GroupValue95% CI
V1140.3
PCV130.3
Percentage of Participants Meeting the Serotype Specific Immunoglobulin G Threshold Value of ≥0.35 μg/mL for Each Serotype in V114 After Dose 3 Primary · 30 Days after Dose 3, up to a total of 11 months

The anti-pneumococcal polysaccharide (PnPs) serotype-specific immunoglobulin G (IgG) response rates (percentage of participants meeting serotype-specific IgG threshold value of ≥0.35 μg/mL of participants administered V114 versus participants administered PCV13) for the 15 serotypes contained in V114 were determined using an electrochemiluminescence assay.

Serotype 1 (Shared)
GroupValue95% CI
V11499.7
PCV13100.0
Serotype 3 (Shared)
GroupValue95% CI
V114100.0
PCV1397.7
Serotype 4 (Shared)
GroupValue95% CI
V114100.0
PCV13100.0
Serotype 5 (Shared)
GroupValue95% CI
V11498.8
PCV13100.0
Serotype 6A (Shared)
GroupValue95% CI
V11499.1
PCV13100.0
Serotype 6B (Shared)
GroupValue95% CI
V11495.0
PCV1398.8
Serotype 7F (Shared)
GroupValue95% CI
V11499.7
PCV13100.0
Serotype 9V (Shared)
GroupValue95% CI
V11499.7
PCV13100.0
Geometric Mean Concentration of Serotype-Specific IgG for the 13 Shared Serotypes in V114 and PCV13 After Dose 3 Primary · 30 Days after Dose 3, up to a total of 11 months

The anti-PnPs serotype-specific IgG Geometric Mean Concentrations (GMCs) of participants administered V114 versus participants administered PCV13 for the 13 serotypes shared in V114 and PCV13 were determined using an electrochemiluminescence assay.

Serotype 1 (Shared)
GroupValue95% CI
V1142.392.19 – 2.62
PCV133.953.61 – 4.32
Serotype 3 (Shared)
GroupValue95% CI
V1142.632.39 – 2.89
PCV131.421.29 – 1.56
Serotype 4 (Shared)
GroupValue95% CI
V1142.982.71 – 3.27
PCV133.543.23 – 3.89
Serotype 5 (Shared)
GroupValue95% CI
V1142.592.32 – 2.89
PCV133.353.00 – 3.74
Serotype 6A (Shared)
GroupValue95% CI
V1142.512.26 – 2.79
PCV134.454.00 – 4.94
Serotype 6B (Shared)
GroupValue95% CI
V1142.462.14 – 2.82
PCV134.173.63 – 4.79
Serotype 7F (Shared)
GroupValue95% CI
V1144.383.95 – 4.85
PCV135.224.71 – 5.78
Serotype 9V (Shared)
GroupValue95% CI
V1143.092.80 – 3.41
PCV133.553.22 – 3.92
GMC of Serotype-Specific IgG for the 2 Unique V114 Serotypes After Dose 3 Secondary · 30 days after Dose 3, up to a total of 11 months

The anti-PnPs serotype-specific IgG GMCs of participants administered V114 versus participants administered PCV13 for the 2 unique V114 serotypes was determined using an electrochemiluminescence assay.

Serotype 22F (Unique to V114)
GroupValue95% CI
V1146.595.95 – 7.30
PCV130.060.06 – 0.07
Serotype 33F (Unique to V114)
GroupValue95% CI
V1141.851.60 – 2.14
PCV130.060.05 – 0.07
Percentage of Participants Meeting the Serotype Specific IgG Threshold Value of ≥0.35 μg/mL for Each Serotype in V114 After Dose 4 Secondary · 30 Days after Dose 4, up to a total of 14 months

The anti-PnPs serotype-specific IgG response rates (percentage of participants meeting serotype-specific IgG threshold value of ≥0.35 μg/mL of participants administered V114 versus participants administered PCV13) for the 15 serotypes contained in V114 were determined using an electrochemiluminescence assay.

Serotype 1 (Shared)
GroupValue95% CI
V11499.7
PCV13100.0
Serotype 3 (Shared)
GroupValue95% CI
V114100.0
PCV1396.7
Serotype 4 (Shared)
GroupValue95% CI
V11499.7
PCV13100.0
Serotype 5 (Shared)
GroupValue95% CI
V114100.0
PCV13100.0
Serotype 6A (Shared)
GroupValue95% CI
V114100.0
PCV13100.0
Serotype 6B (Shared)
GroupValue95% CI
V114100.0
PCV13100.0
Serotype 7F (Shared)
GroupValue95% CI
V114100.0
PCV13100.0
Serotype 9V (Shared)
GroupValue95% CI
V114100.0
PCV13100.0
GMC of Serotype-Specific IgG for Each Serotype in V114 After Dose 4 Secondary · 30 Days after Dose 4, up to a total of 14 months

The anti-PnPs serotype-specific IgG GMCs of participants administered V114 versus participants administered PCV13 for the 15 serotypes contained in V114 was determined using an electrochemiluminescence assay.

Serotype 1 (Shared)
GroupValue95% CI
V1142.742.47 – 3.04
PCV135.194.68 – 5.77
Serotype 3 (Shared)
GroupValue95% CI
V1142.181.97 – 2.41
PCV131.281.15 – 1.41
Serotype 4 (Shared)
GroupValue95% CI
V1142.912.57 – 3.30
PCV133.182.81 – 3.59
Serotype 5 (Shared)
GroupValue95% CI
V1144.433.96 – 4.95
PCV136.655.95 – 7.43
Serotype 6A (Shared)
GroupValue95% CI
V1146.055.36 – 6.81
PCV139.418.35 – 10.60
Serotype 6B (Shared)
GroupValue95% CI
V1148.037.12 – 9.05
PCV1310.889.66 – 12.26
Serotype 7F (Shared)
GroupValue95% CI
V1145.805.15 – 6.54
PCV137.156.35 – 8.05
Serotype 9V (Shared)
GroupValue95% CI
V1144.273.79 – 4.81
PCV135.184.60 – 5.83
Geometric Mean Titer of Serotype-Specific Opsonophagocytic Activity for Each Serotype in V114 After Dose 3 Secondary · 30 Days after Dose 3, up to a total of 11 months

The anti-PnPs serotype-specific opsonophagocytic activity (OPA) and geometric mean titers (GMTs) of participants administered V114 versus participants administered PCV13 for the 15 serotypes contained in V114 was determined using a multiplexed opsonophagocytic assay.

Serotype 1 (Shared)
GroupValue95% CI
V114211.51180.48 – 247.86
PCV13322.44275.23 – 377.76
Serotype 3 (Shared)
GroupValue95% CI
V114660.68586.60 – 744.11
PCV13471.43418.48 – 531.08
Serotype 4 (Shared)
GroupValue95% CI
V1143984.873537.66 – 4488.62
PCV134118.163656.82 – 4637.70
Serotype 5 (Shared)
GroupValue95% CI
V1141241.691098.82 – 1403.14
PCV131358.431202.35 – 1534.79
Serotype 6A (Shared)
GroupValue95% CI
V1149124.967894.53 – 10547.16
PCV1311956.6410340.85 – 13824.91
Serotype 6B (Shared)
GroupValue95% CI
V1148416.197243.92 – 9778.18
PCV1310421.948972.87 – 12105.02
Serotype 7F (Shared)
GroupValue95% CI
V11422324.4119365.68 – 25735.19
PCV1327396.2823771.84 – 31573.33
Serotype 9V (Shared)
GroupValue95% CI
V1142725.292399.27 – 3095.62
PCV133338.402939.75 – 3791.11
GMT of Serotype-Specific OPA for Each Serotype in V114 After Dose 4 Secondary · 30 Days after Dose 4, up to a total of 14 months

The anti-PnPs serotype-specific opsonophagocytic activity (OPA) and geometric mean titers (GMTs) of participants administered V114 versus participants administered PCV13 for the 15 serotypes contained in V114 was determined using a multiplexed opsonophagocytic assay.

Serotype 1 (Shared)
GroupValue95% CI
V114453.42327.21 – 628.32
PCV13854.50616.64 – 1184.10
Serotype 3 (Shared)
GroupValue95% CI
V1141444.001166.36 – 1787.72
PCV13893.97720.25 – 1109.58
Serotype 4 (Shared)
GroupValue95% CI
V1144531.523592.99 – 5715.21
PCV136264.944957.63 – 7916.97
Serotype 5 (Shared)
GroupValue95% CI
V1141853.081439.01 – 2386.30
PCV132151.951669.81 – 2773.30
Serotype 6A (Shared)
GroupValue95% CI
V11412553.0610072.11 – 15645.13
PCV1317476.2413999.28 – 21816.75
Serotype 6B (Shared)
GroupValue95% CI
V1149218.647346.96 – 11567.14
PCV1314041.5311171.79 – 17648.42
Serotype 7F (Shared)
GroupValue95% CI
V11415451.9612500.49 – 19100.31
PCV1318039.0414593.41 – 22298.22
Serotype 9V (Shared)
GroupValue95% CI
V1143259.242548.05 – 4168.93
PCV135050.893957.89 – 6445.73

Adverse events — posted to ClinicalTrials.gov

Time frame: Non-serious adverse events: Up to 14 days after each vaccination, up to a total of 13.5 months; Serious adverse events: Approximately 1 month after Dose 4 (Up to 14 months); All-cause mortality: Up to 17 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

V114
Serious: 24/347 (7%)
Deaths: 0/347
PCV13
Serious: 23/346 (7%)
Deaths: 0/347

Serious adverse events (33 terms)

ReactionSystemV114PCV13
Respiratory syncytial virus infectionInfections and infestations
Urinary tract infectionInfections and infestations
Food allergyImmune system disorders
PneumoniaInfections and infestations
Bacterial infectionInfections and infestations
BronchitisInfections and infestations
Respiratory syncytial virus bronchitisInfections and infestations
AsthmaRespiratory, thoracic and mediastinal disorders
Kawasaki's diseaseVascular disorders
HamartomaCongenital, familial and genetic disorders
IntussusceptionGastrointestinal disorders
PyrexiaGeneral disorders
Anaphylactic reactionImmune system disorders
Milk allergyImmune system disorders
Adenovirus infectionInfections and infestations
BronchiolitisInfections and infestations
COVID-19Infections and infestations
Escherichia urinary tract infectionInfections and infestations
Gastroenteritis norovirusInfections and infestations
Gastroenteritis viralInfections and infestations
Lymphadenitis bacterialInfections and infestations
Nephritis bacterialInfections and infestations
Pneumonia bacterialInfections and infestations
Pneumonia respiratory syncytial viralInfections and infestations
Pneumonia viralInfections and infestations
Other adverse events (16 terms — click to expand)

ReactionSystemV114PCV13
Injection site erythemaGeneral disorders
Injection site indurationGeneral disorders
Injection site swellingGeneral disorders
PyrexiaGeneral disorders
IrritabilityPsychiatric disorders
SomnolenceNervous system disorders
Injection site painGeneral disorders
Decreased appetiteMetabolism and nutrition disorders
NasopharyngitisInfections and infestations
DiarrhoeaGastrointestinal disorders
ErythemaSkin and subcutaneous tissue disorders
Skin indurationSkin and subcutaneous tissue disorders
Upper respiratory tract infectionInfections and infestations
RhinorrhoeaRespiratory, thoracic and mediastinal disorders
Eczema infantileSkin and subcutaneous tissue disorders
RashSkin and subcutaneous tissue disorders

Most-reported serious reactions: Respiratory syncytial virus infection, Urinary tract infection, Food allergy, Pneumonia, Bacterial infection, Bronchitis, Respiratory syncytial virus bronchitis, Asthma.

Data from ClinicalTrials.gov NCT04384107 adverse events section.

Sponsor's own description

The purpose of this clinical study is to evaluate the safety and immunogenicity of a 4-dose schedule (3-dose primary series followed by a toddler dose) of V114 compared with Pneumococcal 13-valent Conjugate Vaccine (PCV13). The hypotheses are that: 1) V114 is non-inferior to PCV13 for the 13 shared serotypes between V114 and PCV13 based on the response rates at 30 days following dose 3; 2) V114 is non-inferior to PCV13 for the 2 unique V114 serotypes based on the response rate of the 2 unique V114 serotypes at 30 days following dose 3; 3) V114 is non-inferior to PCV13 for the 13 shared serotypes between V114 and PCV13 based on anti-pneumococcal polysaccharide (PnPs) serotype-specific Immunoglobulin G (IgG) geometric mean concentrations (GMCs) at 30 days following dose 3.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

  1. Safety and immunogenicity of 15-valent pneumococcal conjugate vaccine in Japanese healthy infants: A phase III study (V114-033).
    Suzuki H, Fujita H, Iwai K, Kuroki H, et al · · 2023 · cited 2× · PMID 37344262 · DOI 10.1016/j.vaccine.2023.05.064

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Trials by the same sponsor.

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