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Safety and Immunogenicity of Catch-up Vaccination Regimens of V114 (V114-024)

Phase 3
Completed
Conditions
Pneumococcal Infections
Interventions
Biological: V114
Biological: Prevnar 13®
Registration Number
NCT03885934
Lead Sponsor
Merck Sharp & Dohme LLC
Brief Summary

The purpose of this study is 1) to evaluate the safety and tolerability of V114 with respect to the proportion of participants with adverse events (AEs) and 2) to evaluate the anti-pneumococcal polysaccharide (PnPs) serotype-specific Immunoglobulin G (IgG) Geometric Mean Concentrations (GMCs) at 30 days following the last dose for each vaccination group. There is no formal hypothesis testing in this study.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
606
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
V114, Schedule C: Participants 2-17 yearsV114Each participant received a 0.5 mL IM injection for 2 to 17 years of age (PCV-naïve or PCV-experienced) (1 dose). Single dose administered at randomization and at least 8 weeks after previous PCV for participants who were PCV-experienced.
V114, Schedule B: Participants 12-23 monthsV114Each participant received a 0.5 mL IM injection for 12 to 23 months of age (PCV-naïve)(2 doses). Dose 1: at randomization, and Dose 2: 8 to 12 weeks after Dose 1.
Prevnar 13®, Schedule B: Participants 12-23 monthsPrevnar 13®Each participant received a 0.5 mL IM injection for 12 to 23 months of age (PCV-naïve)(2 doses). Dose 1: at randomization, and Dose 2: 8 to 12 weeks after Dose 1.
Prevnar 13®, Schedule A: Participants 7-11 monthsPrevnar 13®Each participant received a 0.5 mL IM injection for 7 to 11 months of age (PCV-naïve)(3 doses). Dose 1: at randomization, Dose 2: 4 to 8 weeks after Dose 1, and Dose 3: 8 to 12 weeks after Dose 2 and ≥12 months of age.
Prevnar 13®, Schedule C: Participants 2-17 yearsPrevnar 13®Each participant received a 0.5 mL IM injection for 2 to 17 years of age (PCV-naïve or PCV-experienced)(1 dose). Single dose administered at randomization and at least 8 weeks after previous PCV for participants who were PCV-experienced.
V114, Schedule A: Participants 7-11 monthsV114Each participant received a 0.5 mL intramuscular (IM) injection for 7 to 11 months of age (Pneumococcal conjugate vaccine \[PCV\]-naïve)(3 doses). Dose 1: at randomization, Dose 2: 4 to 8 weeks after Dose 1, and Dose 3: 8 to 12 weeks after Dose 2 and ≥12 months of age.
Primary Outcome Measures
NameTimeMethod
Geometric Mean Concentration of Serotype-specific Immunoglobulin G - Schedule A: 7-11 Months30 days post last vaccination

The geometric mean concentration (GMC) of immunoglobulin G (IgG) serotype-specific antibodies to the 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) included in V114 and Prevnar 13®; and two serotypes (22F and 33F) which are unique to V114 was determined. Sera from participants was used to measure vaccine-induced anti-pneumococcal polysaccharides (PnPs) serotype-specific IgG for all the 15 serotypes using pneumococcal electrochemiluminescence (PnECL) assay. The within-group 95% confidence intervals (CIs) were derived by exponentiating the CIs of the mean of the natural log values based on the t-distribution.

GMC of Serotype-specific IgG - Schedule B: 12-23 Months30 days post last vaccination

The GMC of IgG serotype-specific antibodies to the 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) included in V114 and Prevnar 13®; and two serotypes (22F and 33F) which are unique to V114 was determined. Sera from participants was used to measure vaccine-induced anti-PnPs serotype-specific IgG for all the 15 serotypes using pneumococcal electrochemiluminescence (PnECL) assay. The within-group 95% CIs were derived by exponentiating the CIs of the mean of the natural log values based on the t-distribution.

GMC of Serotype-specific IgG - Schedule C: 2-17 Years30 days post vaccination

The GMC of IgG serotype-specific antibodies to the 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) included in V114 and Prevnar 13®; and two serotypes (22F and 33F) which are unique to V114 was determined. Sera from participants was used to measure vaccine-induced anti-PnPs serotype-specific IgG for all the 15 serotypes using pneumococcal electrochemiluminescence (PnECL) assay. The within-group 95% CIs were derived by exponentiating the CIs of the mean of the natural log values based on the t-distribution.

Percentage of Participants With Solicited Injection-site Adverse Events - Schedule A: 7-11 MonthsUp to 14 days post any vaccination

An adverse event (AE) is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. The parent/guardian of the participant recorded the presence of any vaccination report card (VRC)-prompted injection-site AEs that occurred in the 14 days after any vaccination. The percentage of participants with an injection-site AE prompted on the VRC (redness/erythema, hardness/induration, swelling, and pain) was summarized.

Percentage of Participants With Solicited Injection-site AEs - Schedule B: 12-23 MonthsUp to 14 days post any vaccination

An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. The parent/guardian of the participant recorded the presence of any vaccination report card (VRC)-prompted injection-site AEs that occurred in the 14 days after any vaccination. The percentage of participants with an injection-site AE prompted on the VRC (redness/erythema, hardness/induration, swelling, and pain) was summarized.

Percentage of Participants With Solicited Systemic AEs - Schedule C: 2-17 YearsUp to 14 days post vaccination

An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. The parent/guardian of the participant recorded the presence of any VRC-prompted systemic AEs that occurred in the 14 days after any vaccination. For participants 7 months to \<3 years of age at enrollment, solicited systemic AEs include irritability, drowsiness/somnolence, appetite lost/decreased appetite, and hives or welts/urticaria. For participants ≥3 years of age at enrollment, solicited systemic AEs include muscle pain/ myalgia, joint pain/arthralgia, headache, tiredness/fatigue, and hives or welts/urticaria. The percentage of participants with a systemic AE was summarized.

Percentage of Participants With Solicited Systemic AEs - Schedule A: 7-11 MonthsUp to 14 days post any vaccination

An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. The parent/guardian of the participant recorded the presence of any VRC-prompted systemic AEs that occurred in the 14 days after any vaccination. For participants 7 months to \<3 years of age at enrollment, solicited systemic AEs include irritability, drowsiness/somnolence, appetite lost/decreased appetite, and hives or welts/urticaria. The percentage of participants with a systemic AE was summarized.

Percentage of Participants With at Least 1 Vaccine-related SAE - Schedule B: 12-23 MonthsUp to ~6 months post final vaccination

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. Estimated within-group CIs are calculated based on the exact binomial method proposed by Clopper and Pearson and are provided in accordance with the statistical analysis plan.

Percentage of Participants With Solicited Systemic AEs - Schedule B: 12-23 MonthsUp to 14 days post any vaccination

An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. The parent/guardian of the participant recorded the presence of any VRC-prompted systemic AEs that occurred in the 14 days after any vaccination. For participants 7 months to \<3 years of age at enrollment, solicited systemic AEs include irritability, drowsiness/somnolence, appetite lost/decreased appetite, and hives or welts/urticaria. The percentage of participants with a systemic AE was summarized.

Percentage of Participants With at Least 1 Vaccine-related Serious Adverse Event - Schedule A: 7-11 MonthsUp to ~6 months post final vaccination

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. Estimated within-group CIs are calculated based on the exact binomial method proposed by Clopper and Pearson and are provided in accordance with the statistical analysis plan.

Percentage of Participants With Solicited Injection-site AEs - Schedule C: 2-17 YearsUp to 14 days post vaccination

An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. The parent/guardian of the participant recorded the presence of any vaccination report card (VRC)-prompted injection-site AEs that occurred in the 14 days after any vaccination. The percentage of participants with an injection-site AE prompted on the VRC (redness/erythema, hardness/induration, swelling, and pain) was summarized.

Percentage of Participants With at Least 1 Vaccine-related SAE - Schedule C: 2-17 YearsUp to ~6 months post vaccination

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.

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants Meeting Serotype-specific IgG Threshold Value of ≥0.35 μg/mL for Each of the 15 Serotypes - Schedule A: 7-11 Months30 days post final vaccination

Sera from participants was used to measure vaccine-induced anti-PnPs serotype-specific IgG for all the 15 serotypes using PnECL assay. The percentage that achieved the IgG threshold value of ≥0.35 μg/mL was summarized. Estimated within-group CIs are calculated based on the exact binomial method proposed by Clopper and Pearson and are provided in accordance with the statistical analysis plan.

Percentage of Participants Meeting Serotype-specific IgG Threshold Value of ≥0.35 μg/mL for Each of the 15 Serotypes - Schedule B: 12-23 Months30 days post final vaccination

Sera from participants was used to measure vaccine-induced anti-PnPs serotype-specific IgG for all the 15 serotypes using PnECL assay. The percentage that achieved the IgG threshold value of ≥0.35 μg/mL was summarized. Estimated within-group CIs are calculated based on the exact binomial method proposed by Clopper and Pearson and are provided in accordance with the statistical analysis plan. The analysis population included all randomized participants without deviations from the protocol that may substantially affect the results of the immunogenicity endpoint.

Percentage of Participants Meeting Serotype-specific IgG Threshold Value of ≥0.35 μg/mL for Each of the 15 Serotypes - Schedule C: 2-17 Years30 days post vaccination

Sera from participants was used to measure vaccine-induced anti-PnPs serotype-specific IgG for all the 15 serotypes using PnECL assay. The percentage that achieved the IgG threshold value of ≥0.35 μg/mL was summarized. Estimated within-group CIs are calculated based on the exact binomial method proposed by Clopper and Pearson and are provided in accordance with the statistical analysis plan.

Trial Locations

Locations (26)

Uniwersytecki Szpital Kliniczny ( Site 0207)

🇵🇱

Wroclaw, Poland

Research Institute of Children Infections ( Site 0301)

🇷🇺

Saint Petersburg, Russian Federation

Children s City Polyclinic No. 45 of the Nevsky District ( Site 0312)

🇷🇺

St.Petersburg, Russian Federation

Tampereen yliopisto - Tampereen rokotetutkimusklinikka ( Site 0001)

🇫🇮

Tampere, Finland

Tampereen yliopisto Porin rokotetutkimusklinikka ( Site 0008)

🇫🇮

Pori, Finland

Seinajoki Vaccine Research Center ( Site 0010)

🇫🇮

Seinajoki, Finland

Sabah Womens & Childrens Hospital ( Site 0902)

🇲🇾

Kota Kinabalu, Malaysia

Przychodnia Vitamed Gaaj i Cichomski Spolka Jawna ( Site 0212)

🇵🇱

Bydgoszcz, Poland

Tampereen yliopisto Etelä-Helsingin rokotetutkimusklinikka ( Site 0005)

🇫🇮

Helsinki, Finland

Tampereen yliopisto Turun rokotetutkimusklinikka ( Site 0002)

🇫🇮

Turku, Finland

MAI Childrens City Clinical Hospital 11 ( Site 0305)

🇷🇺

Ekaterinburg, Russian Federation

Siriraj Hospital ( Site 0600)

🇹🇭

Bangkok, Thailand

Central Clinical Hospital of Russian Academy Science ( Site 0317)

🇷🇺

Moscow, Russian Federation

Tampereen yliopisto Ita-Helsingin rokotetutkimusklinikka ( Site 0006)

🇫🇮

Helsinki, Finland

Tampereen yliopisto Espoon rokotetutkimusklinikka ( Site 0007)

🇫🇮

Espoo, Finland

Srinagarind Hospital ( Site 0602)

🇹🇭

Khonkaen, Thailand

Tampereen yliopisto Kokkolan rokotetutkimusklinikka ( Site 0009)

🇫🇮

Kokkola, Finland

Tampereen yliopisto Järvenpään rokotetutkimusklinikka ( Site 0003)

🇫🇮

Jarvenpaa, Finland

University Malaya Medical Centre ( Site 0901)

🇲🇾

Kuala Lumpur, Malaysia

SPZOZ im. Dzieci Warszawy w Dziekanowie Lesnym ( Site 0209)

🇵🇱

Lomianki, Poland

NZ Lecznictwa Ambulatoryjnego - Michalkowice - Jarosz i Partnerzy ( Site 0211)

🇵🇱

Siemianowice Slaskie, Poland

Vaccine Trial Center Faculty of Tropical Medicine ( Site 0603)

🇹🇭

Bangkok, Thailand

Tampereen yliopisto Oulun rokotetutkimusklinikka ( Site 0004)

🇫🇮

Oulu, Finland

Spec Zesp Opieki Zdrowotnej nad Matka i Dzieckiem w Poznaniu ( Site 0213)

🇵🇱

Poznan, Poland

Chulalongkorn University ( Site 0601)

🇹🇭

Bangkok, Thailand

Centrum Medyczne Pratia Bydgoszcz ( Site 0210)

🇵🇱

Bydgoszcz, Poland

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