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

NCT03885934 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: V114-0242018-003706-88
• Study Type: interventional
• Target: 606
• Locations: 5 countries
• Sites: 26

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.

Conditions

Pneumococcal Infections

Outcome Measures

Primary Outcomes (12)

• Geometric Mean Concentration of Serotype-specific Immunoglobulin G - Schedule A: 7-11 Months

  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.

  30 days post last vaccination

• GMC of Serotype-specific IgG - Schedule B: 12-23 Months

  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.

  30 days post last vaccination

• GMC of Serotype-specific IgG - Schedule C: 2-17 Years

  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.

  30 days post vaccination

• Percentage of Participants With Solicited Injection-site Adverse Events - Schedule A: 7-11 Months

  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.

  Up to 14 days post any vaccination

• Percentage of Participants With Solicited Injection-site AEs - Schedule B: 12-23 Months

  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.

  Up to 14 days post any vaccination

• Percentage of Participants With Solicited Injection-site AEs - Schedule C: 2-17 Years

  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.

  Up to 14 days post vaccination

• Percentage of Participants With Solicited Systemic AEs - Schedule A: 7-11 Months

  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.

  Up to 14 days post any vaccination

• Percentage of Participants With Solicited Systemic AEs - Schedule B: 12-23 Months

  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.

  Up to 14 days post any vaccination

• Percentage of Participants With Solicited Systemic AEs - Schedule C: 2-17 Years

  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.

  Up to 14 days post vaccination

• Percentage of Participants With at Least 1 Vaccine-related Serious Adverse Event - Schedule A: 7-11 Months

  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.

  Up to ~6 months post final vaccination

• Percentage of Participants With at Least 1 Vaccine-related SAE - Schedule B: 12-23 Months

  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.

  Up to ~6 months post final vaccination

• Percentage of Participants With at Least 1 Vaccine-related SAE - Schedule C: 2-17 Years

  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.

  Up to ~6 months post vaccination

Secondary Outcomes (3)

• Percentage of Participants Meeting Serotype-specific IgG Threshold Value of ≥0.35 μg/mL for Each of the 15 Serotypes - Schedule A: 7-11 Months

  30 days post final vaccination

• Percentage of Participants Meeting Serotype-specific IgG Threshold Value of ≥0.35 μg/mL for Each of the 15 Serotypes - Schedule B: 12-23 Months

  30 days post final vaccination

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

  30 days post vaccination

Study Arms (6)

V114, Schedule A: Participants 7-11 months

EXPERIMENTAL

Each 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.

Biological: V114

Prevnar 13®, Schedule A: Participants 7-11 months

ACTIVE COMPARATOR

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.

Biological: Prevnar 13®

V114, Schedule B: Participants 12-23 months

EXPERIMENTAL

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.

Biological: V114

Prevnar 13®, Schedule B: Participants 12-23 months

ACTIVE COMPARATOR

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.

Biological: Prevnar 13®

V114, Schedule C: Participants 2-17 years

EXPERIMENTAL

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.

Biological: V114

Prevnar 13®, Schedule C: Participants 2-17 years

ACTIVE COMPARATOR

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.

Biological: Prevnar 13®

Interventions

V114 BIOLOGICAL

V114 15-valent PCV containing 13 serotypes present in Prevnar 13® (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) and 2 unique serotypes (22F and 33F) in each 0.5 mL IM administration

Also known as: Pneumococcal 15-valent Conjugate Vaccine, VAXNEUVANCE™

V114, Schedule A: Participants 7-11 months; V114, Schedule B: Participants 12-23 months; V114, Schedule C: Participants 2-17 years

Prevnar 13® BIOLOGICAL

Prevnar 13® 13-valent PCV containing 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) in each 0.5 mL IM administration.

Also known as: PCV13

Prevnar 13®, Schedule A: Participants 7-11 months; Prevnar 13®, Schedule B: Participants 12-23 months; Prevnar 13®, Schedule C: Participants 2-17 years

Eligibility Criteria

• Age: 7 Months - 17 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Not be pregnant or breastfeeding
• Not be a woman of childbearing potential
• If of a woman of childbearing potential, agree to follow the contraceptive guidance during the treatment period and for at least 6 weeks after the last dose of study intervention
• Has a legally acceptable representative who understands the study procedures, alternate treatments available, and risks involved with the study and voluntarily agrees to participate by giving written informed consent

You may not qualify if:

• History of invasive pneumococcal disease (IPD)
• Known hypersensitivity to any component of the PCV or any diphtheria toxoid-containing vaccine
• Had a recent febrile illness occurring within 72 hours prior to receipt of study vaccine
• Known or suspected impairment of immunological function
• History of congenital or acquired immunodeficiency
• Has or his/her mother has a documented human immunodeficiency virus (HIV) infection
• Known or history of functional or anatomic asplenia
• Has failure to thrive based on the clinical judgement of the investigator
• Has a bleeding disorder contraindicating intramuscular vaccination
• Has a history of autoimmune disease (including but not limited to systemic lupus erythematosus, antiphospholipid syndrome, Behcet's disease, autoimmune thyroid disease, polymyositis and dermatomyositis, scleroderma, type 1 diabetes mellitus, or other autoimmune disorders)
• Has known neurologic or cognitive behavioral disorder, including encephalitis/myelitis, acute disseminating encephalomyelitis, pervasive development disorder, and related disorders
• Is 7 to 23 months of age and has received a dose of a pneumococcal vaccine prior to study entry based on medical record. Participants ≥2 years of age could have received a PCV at least 8 weeks prior to study entry as follows: a partial regimen of Prevnar™,Synflorix™, or Prevnar 13™ or a full regimen of Prevnar™ or Synflorix™ based on local guidelines. Participants should not have received any dose of a pneumococcal polysaccharide vaccine
• Has received other licensed non-live vaccines within 14 days before receipt of study vaccine. Exception: Inactivated influenza vaccine may be administered but must be given at least 7 days before receipt of study vaccine or at least 15 days after receipt of study vaccine
• Has received a licensed live vaccine within 30 days before receipt of study vaccine
• Has received a blood transfusion or blood products, including immunoglobulins, within 6 months before receipt of study vaccine

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (26)

Tampereen yliopisto Espoon rokotetutkimusklinikka ( Site 0007)

Espoo, 02230, Finland

Location

Tampereen yliopisto Etelä-Helsingin rokotetutkimusklinikka ( Site 0005)

Helsinki, 00100, Finland

Location

Tampereen yliopisto Ita-Helsingin rokotetutkimusklinikka ( Site 0006)

Helsinki, 00930, Finland

Location

Tampereen yliopisto Järvenpään rokotetutkimusklinikka ( Site 0003)

Jarvenpaa, 04400, Finland

Location

Tampereen yliopisto Kokkolan rokotetutkimusklinikka ( Site 0009)

Kokkola, 67100, Finland

Location

Tampereen yliopisto Oulun rokotetutkimusklinikka ( Site 0004)

Oulu, 90220, Finland

Location

Tampereen yliopisto Porin rokotetutkimusklinikka ( Site 0008)

Pori, 28100, Finland

Location

Seinajoki Vaccine Research Center ( Site 0010)

Seinäjoki, 60100, Finland

Location

Tampereen yliopisto - Tampereen rokotetutkimusklinikka ( Site 0001)

Tampere, 33100, Finland

Location

Tampereen yliopisto Turun rokotetutkimusklinikka ( Site 0002)

Turku, 20520, Finland

Location

Sabah Womens & Childrens Hospital ( Site 0902)

Kota Kinabalu, 88996, Malaysia

Location

University Malaya Medical Centre ( Site 0901)

Kuala Lumpur, 59100, Malaysia

Location

Przychodnia Vitamed Gaaj i Cichomski Spolka Jawna ( Site 0212)

Bydgoszcz, 85-079, Poland

Location

Centrum Medyczne Pratia Bydgoszcz ( Site 0210)

Bydgoszcz, 85-796, Poland

Location

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

Poznan, 61-709, Poland

Location

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

Siemianowice Śląskie, 41-103, Poland

Location

Uniwersytecki Szpital Kliniczny ( Site 0207)

Wroclaw, 50-368, Poland

Location

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

Łomianki, 05-092, Poland

Location

Central Clinical Hospital of Russian Academy Science ( Site 0317)

Moscow, 119333, Russia

Location

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

Saint Petersburg, 193312, Russia

Location

Research Institute of Children Infections ( Site 0301)

Saint Petersburg, 197022, Russia

Location

MAI Childrens City Clinical Hospital 11 ( Site 0305)

Yekaterinburg, 620028, Russia

Location

Chulalongkorn University ( Site 0601)

Bangkok, 10330, Thailand

Location

Vaccine Trial Center Faculty of Tropical Medicine ( Site 0603)

Bangkok, 10400, Thailand

Location

Siriraj Hospital ( Site 0600)

Bangkok, 10700, Thailand

Location

Srinagarind Hospital ( Site 0602)

Khonkaen, 40002, Thailand

Location

Related Publications (1)

• Banniettis N, Wysocki J, Szenborn L, Phongsamart W, Pitisuttithum P, Ramet M, Richmond P, Shi Y, Dagan R, Good L, Papa M, Lupinacci R, McFetridge R, Tamms G, Churchill C, Musey L, Bickham K; V114-024 PNEU-PLAN study group. A phase III, multicenter, randomized, double-blind, active comparator-controlled study to evaluate the safety, tolerability, and immunogenicity of catch-up vaccination regimens of V114, a 15-valent pneumococcal conjugate vaccine, in healthy infants, children, and adolescents (PNEU-PLAN). Vaccine. 2022 Oct 19;40(44):6315-6325. doi: 10.1016/j.vaccine.2022.09.003. Epub 2022 Sep 21.

  PMID: 36150974 RESULT

MeSH Terms

Conditions

Pneumococcal Infections

Interventions

13-valent pneumococcal vaccine

Condition Hierarchy (Ancestors)

Streptococcal Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Study Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2019
• First Posted: March 22, 2019
• Study Start: June 25, 2019
• Primary Completion: December 9, 2020
• Study Completion: December 9, 2020
• Last Updated: January 13, 2023
• Results First Posted: September 23, 2021

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share

Locations

RU (4); MY (2); PL (6); TH (4); FI (10)