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NCT03950622: PNEU-AGE

Safety and Immunogenicity of V114 in Healthy Adults (V114-019/PNEU-AGE)

Completed Phase 3 Results posted Last updated 26 April 2021
What this trial tests

Phase 3 trial testing V114 in Pneumococcal Infections in 1,205 participants. Completed in 30 March 2020.

Timeline
13 June 2019
Primary endpoint
30 March 2020
30 March 2020

Quick facts

Lead sponsorMerck Sharp & Dohme LLC
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposeprevention
Enrollment1,205
Start date13 June 2019
Primary completion30 March 2020
Estimated completion30 March 2020
Sites30 locations across Japan, Taiwan, Canada, United States, Spain

Drugs / interventions tested

Conditions studied

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

50 and older, 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 a Solicited Injection-site Adverse Event Primary · Up to Day 5 postvaccination

An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Solicited injection-site AEs consist of redness/erythema, swelling, and tenderness/pain.

Injection site erythema
GroupValue95% CI
V1149.0
Prevnar 13™11.3
Injection site pain
GroupValue95% CI
V11454.0
Prevnar 13™42.3
Injection site swelling
GroupValue95% CI
V11412.5
Prevnar 13™11.2
Percentage of Participants With Solicited Systemic Adverse Events Primary · Up to Day 14 postvaccination

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 vaccination with V114 or Prevnar 13™, the percentage of participants with solicited systemic AEs was assessed. The solicited systemic AEs assessed were muscle pain/myalgia, joint pain/arthralgia, headache, and tiredness/fatigue.

Joint pain/arthralgia
GroupValue95% CI
V1145.3
Prevnar 13™5.5
Tiredness/fatigue
GroupValue95% CI
V11417.4
Prevnar 13™17.3
Headache
GroupValue95% CI
V11411.6
Prevnar 13™13.0
Muscle pain/myalgia
GroupValue95% CI
V11415.4
Prevnar 13™12.0
Percentage of Participants With a Vaccine-related Serious Adverse Event Primary · Up to Month 6

A serious adverse event (SAE) is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires inpatient hospitalization or prolongs existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is another important medical event. SAEs that are reported to be at least possibly related by the investigator to study vaccination will be summarized.

GroupValue95% CI
V1140.0
Prevnar 13™0.0
Geometric Mean Titer of Serotype-specific Opsonophagocytic Activity at Day 30 Primary · Day 30

Serotype-specific opsonophagocytic activity (OPA) geometric mean titers (GMTs) (estimated) and GMT ratios with 95% CIs and 1-sided p-values were calculated using a constrained longitudinal data analysis (cLDA) model utilizing data from both vaccination groups. Per the statistical analysis plan, the only CIs calculated were the between-group CIs (for the GMT ratios); within-group CIs were not calculated. OPA for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) were determined using a multiplexed opsonophagocytic assay (MOPA).

Serotype 1 (Shared)
GroupValue95% CI
V114256.3
Prevnar 13™322.6
Serotype 3 (Shared)
GroupValue95% CI
V114216.2
Prevnar 13™135.1
Serotype 4 (Shared)
GroupValue95% CI
V1141125.6
Prevnar 13™1661.6
Serotype 5 (Shared)
GroupValue95% CI
V114447.3
Prevnar 13™563.5
Serotype 6A (Shared)
GroupValue95% CI
V1145407.2
Prevnar 13™5424.5
Serotype 6B (Shared)
GroupValue95% CI
V1144011.7
Prevnar 13™3258.2
Serotype 7F (Shared)
GroupValue95% CI
V1144617.3
Prevnar 13™5880.6
Serotype 9V (Shared)
GroupValue95% CI
V1141817.3
Prevnar 13™2232.9
Percentage of Participants With ≥4 Fold Rise in Serotype-specific OPA for 2 Unique V114 Serotypes Primary · Day 1 (Baseline) and Day 30

Activity for the serotypes contained in Prevnar 13™ and V114 was determined using a multiplexed opsonophagocytic assay (MOPA). The percentage of participants who had ≥4-fold rise in OPA titers were calculated from baseline (Day 1) to 30 days postvaccination (Day 30) for OPA responses for the 2 unique serotypes in V114. The observed response percentage (m/n) included: m=the number of participants with the indicated response divided by n=the number of participants contributing to the analysis. Per the statistical analysis plan, the only CIs calculated were the between-group CIs (for the percenta

Serotype 22F (Unique to V114)
GroupValue95% CI
V11471.4
Prevnar 13™14.3
Serotype 33F (Unique to V114)
GroupValue95% CI
V11456.7
Prevnar 13™6.3
GMT of Serotype-specific OPA for Serotype 3 at Day 30 Secondary · Day 30

Serotype-specific OPA GMTs (estimated) and GMT ratios with 95% CIs and 1-sided p-values were calculated using a cLDA model utilizing data from both vaccination groups. Per the statistical analysis plan, the only CIs calculated were the between-group CIs (for the GMT ratios); within-group CIs were not calculated. OPA for serotype 3 contained in Prevnar 13™ and V114 was determined using a MOPA. The measure type of "number" presented in the data table below for serotype-specific OPA titer is the geometric mean.

GroupValue95% CI
V114216.2
Prevnar 13™135.1
Percentage of Participants With ≥4 Fold Rise in Serotype-specific OPA for Serotype 3 OPA Responses Secondary · Day 1 (Baseline) and Day 30

Activity for serotype 3 contained in Prevnar 13™ and V114 was determined using a MOPA. The observed response percentage of participants (m/n) who had ≥4-fold rise in OPA titers were calculated from baseline to postvaccination. n=Number of participants contributing to the analysis; m=Number of participants with the indicated response. Per the statistical analysis plan, the only CIs calculated were the between-group CIs (for the percentage point difference); within-group CIs were not calculated.

GroupValue95% CI
V11470.2
Prevnar 13™58.7
Geometric Mean Concentration of Serotype-specific IgG at Day 30 Secondary · Day 30

Serotype-specific Immunoglobulin G (IgG) geometric mean concentrations (GMCs) (estimated) and GMC ratios with 95% confidence intervals (CIs) and 1-sided p-values were calculated using a cLDA model utilizing data from both vaccination groups. Per the statistical analysis plan, the only CIs calculated were the between-group CIs (for the GMC ratios); within-group CIs were not calculated. IgG for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) will be determined using an electrochemiluminescence assay. The measure type of "numbe

Serotype 1 (Shared)
GroupValue95% CI
V1145.30
Prevnar 13™7.34
Serotype 3 (Shared)
GroupValue95% CI
V1140.96
Prevnar 13™0.64
Serotype 4 (Shared)
GroupValue95% CI
V1141.88
Prevnar 13™2.62
Serotype 5 (Shared)
GroupValue95% CI
V1144.57
Prevnar 13™5.56
Serotype 6A (Shared)
GroupValue95% CI
V1147.21
Prevnar 13™7.01
Serotype 6B (Shared)
GroupValue95% CI
V1148.60
Prevnar 13™6.19
Serotype 7F (Shared)
GroupValue95% CI
V1146.18
Prevnar 13™8.09
Serotype 9V (Shared)
GroupValue95% CI
V1144.77
Prevnar 13™5.52
Geometric Mean Fold Rise in Serotype-specific OPA Secondary · Day 1 (Baseline) and Day 30

Activity for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) was determined using a Multiplexed Opsonophagocytic Assay. Geometric mean fold rise (GMFR) is defined as the geometric mean of the ratio of concentration at Day 30 after vaccination divided by concentration at baseline.

Serotype 1 (Shared)
GroupValue95% CI
V11414.312.5 – 16.4
Prevnar 13™18.716.2 – 21.5
Serotype 3 (Shared)
GroupValue95% CI
V1147.77.0 – 8.6
Prevnar 13™5.24.7 – 5.7
Serotype 4 (Shared)
GroupValue95% CI
V11417.815.7 – 20.3
Prevnar 13™24.421.3 – 27.8
Serotype 5 (Shared)
GroupValue95% CI
V11412.310.7 – 14.2
Prevnar 13™15.313.2 – 17.6
Serotype 6A (Shared)
GroupValue95% CI
V11413.011.4 – 14.9
Prevnar 13™13.311.6 – 15.2
Serotype 6B (Shared)
GroupValue95% CI
V11426.322.4 – 30.8
Prevnar 13™21.618.5 – 25.2
Serotype 7F (Shared)
GroupValue95% CI
V11412.010.3 – 13.9
Prevnar 13™14.112.1 – 16.5
Serotype 9V (Shared)
GroupValue95% CI
V1145.34.8 – 6.0
Prevnar 13™6.35.6 – 7.1
Geometric Mean Fold Rise in Serotype-specific IgG Secondary · Day 1 (Baseline) and Day 30

Activity for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) was determined using an electrochemiluminescence assay. Geometric mean fold rise (GMFR) is defined as the geometric mean of the ratio of concentration at Day 30 after vaccination divided by concentration at baseline.

Serotype 1 (Shared)
GroupValue95% CI
V11410.69.4 – 12.0
Prevnar 13™14.713.1 – 16.6
Serotype 3 (Shared)
GroupValue95% CI
V1146.86.2 – 7.6
Prevnar 13™4.74.2 – 5.1
Serotype 4 (Shared)
GroupValue95% CI
V1148.07.2 – 9.0
Prevnar 13™11.210.0 – 12.5
Serotype 5 (Shared)
GroupValue95% CI
V1144.74.2 – 5.2
Prevnar 13™5.85.2 – 6.5
Serotype 6A (Shared)
GroupValue95% CI
V11419.917.6 – 22.6
Prevnar 13™19.717.4 – 22.3
Serotype 6B (Shared)
GroupValue95% CI
V11419.116.8 – 21.7
Prevnar 13™13.812.3 – 15.6
Serotype 7F (Shared)
GroupValue95% CI
V11412.310.9 – 13.9
Prevnar 13™15.813.9 – 18.0
Serotype 9V (Shared)
GroupValue95% CI
V1149.98.9 – 11.1
Prevnar 13™11.19.9 – 12.4
Percentage of Participants With ≥4-Fold Rise in Serotype-specific OPA Titer Secondary · Day 1 (Baseline) and Day 30

Activity for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) was determined using a multiplexed opsonophagocytic assay. The percentage of participants who had ≥4-fold rise in OPA titers were calculated from baseline to postvaccination.

Serotype 1 (Shared)
GroupValue95% CI
V11475.171.4 – 78.6
Prevnar 13™77.774.0 – 81.0
Serotype 3 (Shared)
GroupValue95% CI
V11470.266.3 – 73.9
Prevnar 13™58.754.5 – 62.7
Serotype 4 (Shared)
GroupValue95% CI
V11479.576.0 – 82.7
Prevnar 13™84.881.6 – 87.6
Serotype 5 (Shared)
GroupValue95% CI
V11471.667.8 – 75.2
Prevnar 13™75.371.6 – 78.8
Serotype 6A (Shared)
GroupValue95% CI
V11476.572.7 – 80.0
Prevnar 13™74.971.1 – 78.5
Serotype 6B (Shared)
GroupValue95% CI
V11481.277.7 – 84.3
Prevnar 13™79.275.6 – 82.4
Serotype 7F (Shared)
GroupValue95% CI
V11466.462.4 – 70.3
Prevnar 13™72.468.5 – 76.1
Serotype 9V (Shared)
GroupValue95% CI
V11454.049.8 – 58.1
Prevnar 13™60.055.9 – 64.1
Percentage of Participants With ≥4-Fold Rise in Serotype-specific IgG Concentration Secondary · Day 1 (Baseline) and Day 30

Activity for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) will be determined using an electrochemiluminescence assay. The percentage of participants who had ≥4-fold rise in IgG concentration are calculated from baseline to postvaccination.

Serotype 1 (Shared)
GroupValue95% CI
V11473.169.4 – 76.7
Prevnar 13™78.474.9 – 81.7
Serotype 3 (Shared)
GroupValue95% CI
V11461.657.5 – 65.5
Prevnar 13™51.447.2 – 55.5
Serotype 4 (Shared)
GroupValue95% CI
V11465.061.0 – 68.9
Prevnar 13™76.072.3 – 79.4
Serotype 5 (Shared)
GroupValue95% CI
V11445.141.0 – 49.2
Prevnar 13™53.449.3 – 57.5
Serotype 6A (Shared)
GroupValue95% CI
V11483.580.3 – 86.4
Prevnar 13™83.480.1 – 86.3
Serotype 6B (Shared)
GroupValue95% CI
V11482.879.5 – 85.8
Prevnar 13™77.573.9 – 80.8
Serotype 7F (Shared)
GroupValue95% CI
V11473.569.7 – 77.0
Prevnar 13™78.675.0 – 81.9
Serotype 9V (Shared)
GroupValue95% CI
V11469.665.7 – 73.3
Prevnar 13™75.571.8 – 79.0

Adverse events — posted to ClinicalTrials.gov

Time frame: Non-serious adverse events: Up to 14 days after vaccination; Serious adverse events and all-cause mortality: Up to ~Month 6 (Up to 194 days after vaccination).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

V114
Serious: 9/602 (1%)
Deaths: 1/604
PCV13
Serious: 13/600 (2%)
Deaths: 1/601

Serious adverse events (23 terms)

ReactionSystemV114PCV13
AnaemiaBlood and lymphatic system disorders
Acute myocardial infarctionCardiac disorders
Angina unstableCardiac disorders
ArrhythmiaCardiac disorders
Atrial fibrillationCardiac disorders
Myocardial infarctionCardiac disorders
Incarcerated umbilical herniaGastrointestinal disorders
Oesophagitis ulcerativeGastrointestinal disorders
DeathGeneral disorders
DiverticulitisInfections and infestations
Viral infectionInfections and infestations
Meniscus injuryInjury, poisoning and procedural complications
Back painMusculoskeletal and connective tissue disorders
OsteoarthritisMusculoskeletal and connective tissue disorders
Basal cell carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastrointestinal carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignantNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Non-small cell lung cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer stage IINeoplasms benign, malignant and unspecified (incl cysts and polyps)
UreterolithiasisRenal and urinary disorders
Pelvic painReproductive system and breast disorders
Acute respiratory failureRespiratory, thoracic and mediastinal disorders
Other adverse events (7 terms — click to expand)

ReactionSystemV114PCV13
Injection site painGeneral disorders
FatigueGeneral disorders
MyalgiaMusculoskeletal and connective tissue disorders
HeadacheNervous system disorders
Injection site swellingGeneral disorders
Injection site erythemaGeneral disorders
ArthralgiaMusculoskeletal and connective tissue disorders

Most-reported serious reactions: Anaemia, Acute myocardial infarction, Angina unstable, Arrhythmia, Atrial fibrillation, Myocardial infarction, Incarcerated umbilical hernia, Oesophagitis ulcerative.

Data from ClinicalTrials.gov NCT03950622 adverse events section.

Sponsor's own description

The purpose of this study is to 1) evaluate the safety and tolerability of V114 and 2) to compare the immune responses of the 15 serotypes contained in V114 with V114 versus Prevnar 13™. The primary hypotheses are that 1) V114 is noninferior to Prevnar 13™ as measured by the serotype specific opsonophagocytic activity (OPA) geometric mean titers (GMTs) for 13 shared serotypes at 30 days postvaccination and that 2) V114 is superior to Prevnar 13™ as measured by serotype-specific OPA GMTs for 2 unique serotypes in V114 at 30 days postvaccination.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

  1. A phase 3 trial of safety, tolerability, and immunogenicity of V114, 15-valent pneumococcal conjugate vaccine, compared with 13-valent pneumococcal conjugate vaccine in adults 50 years of age and older (PNEU-AGE).
    Platt HL, Cardona JF, Haranaka M, Schwartz HI, et al · · 2022 · cited 70× · PMID 34507861 · DOI 10.1016/j.vaccine.2021.08.049
  2. Vaccination of older adults: Influenza, pneumococcal disease, herpes zoster, COVID-19 and beyond.
    Weinberger B. · · 2021 · cited 31× · PMID 34627326 · DOI 10.1186/s12979-021-00249-6
  3. Safety and Immunogenicity of V114, a 15-valent Pneumococcal Conjugate Vaccine, Compared with 13-valent Pneumococcal Conjugate Vaccine in Japanese Adults Aged ≥65 Years: Subgroup Analysis of a Randomized Phase III Trial (PNEU-AGE).
    Kishino H, Sawata M, Igarashi R, Shirakawa M, et al · · 2022 · cited 5× · PMID 35908869 · DOI 10.7883/yoken.jjid.2022.060

Verify or expand the search:

Other trials of V114

Trials testing the same drug.

Other recruiting trials for Pneumococcal Infections

Currently open trials in the same condition.

Other Merck Sharp & Dohme LLC trials

Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03950622.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing