Safety, Tolerability, and Immunogenicity of a 3-dose Regimen of V114 in Healthy Infants (PNEU-PED-EU-2/V114-026)

NCT04016714 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: V114-0262018-003788-70
• Study Type: interventional
• Target: 1,191
• Locations: 5 countries
• Sites: 24

Brief Summary

The purpose of this clinical study is to evaluate the safety and immunogenicity of a 3-dose schedule (2-dose primary series followed by a toddler dose) of pneumococcal conjugate vaccine (PCV) as one of the currently recommended schedules by the World Health Organization (WHO) Strategic Advisory Group of Experts (SAGE) on Immunizations and practiced in many countries. The primary hypotheses are that V114 is non-inferior to Prevenar 13™ for the 13 shared serotypes based on response rates and on anti-pneumococcal polysaccharide (PnPs) serotype-specific Immunoglobulin G (IgG) geometric mean concentrations (GMCs) at 30 days following Dose 3; that V114 is superior to Prevenar 13™ for the 2 serotypes unique to V114 based on the response rates and on anti-PnPs serotype-specific IgG GMCs at 30 days following Dose 3; and that Vaxelis™ administered concomitantly with V114 is non-inferior to Vaxelis™ administered concomitantly with Prevenar 13™ at 30 days following Dose 3 for each antigen included in Vaxelis™.

Conditions

Pneumococcal Infections

Outcome Measures

Primary Outcomes (5)

• Percentage of Participants With a Solicited Injection-site Adverse Event

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

  Day 1 to Day 14 after each vaccination

• Percentage of Participants With a Solicited Systemic Adverse Event

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Solicited systemic AEs included decreased appetite, irritability, somnolence (drowsiness), and urticaria (hives or welts).

  Day 1 to Day 14 after each vaccination

• Percentage of Participants With a Vaccine-related Serious Adverse Event

  A serious adverse event (SAE) is an AE that results in death, 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. SAEs that were reported by the investigator to be at least possibly related to the study vaccination were summarized.

  Up to approximately 6 months after Dose 3 (up to approximately 16 months)

• Percentage of Participants Meeting Serotype-specific Immunoglobulin G (IgG) Threshold Value of ≥0.35 μg/mL 30 Days After Dose 3

  The geometric mean concentration (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 Prevenar 13™ and 2 serotypes (22F and 33F) unique to V114 were quantitated from participants' sera by a multiplex electrochemiluminescence (ECL) assay. Immunoglobulin G for the 15 serotypes contained in V114 vaccine was determined using a pneumococcal electrochemiluminescence (PnECL) assay.

  30 days after Dose 3

• Geometric Mean Concentration (GMC) of Serotype-specific Immunoglobulin G (IgG) 30 Days After Dose 3

  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 Prevenar 13™ and 2 serotypes (22F and 33F) unique to V114 were quantitated from participants' sera by a multiplex electrochemiluminescence (ECL) assay.

  30 days after Dose 3

Secondary Outcomes (5)

• Percentage of Participants Meeting Specified Vaxelis™ Antigen Reponses 30 Days After Dose 3

  30 days after Dose 3

• Percentage of Participants Meeting Serotype-specific IgG Threshold Value of ≥0.35 μg/mL 30 Days After Dose 2

  30 days after Dose 2

• GMC of Serotype-specific IgG 30 Days After Dose 2

  30 days after Dose 2

• Percentage of Participants Meeting Specified Opsonophagocytic Activity (OPA) Responses 30 Days After Dose 3

  30 days after Dose 3

• Geometric Mean Titers (GMTs) of Serotype-specific OPA 30 Days After Dose 3

  30 days after Dose 3

Study Arms (2)

V114

EXPERIMENTAL

Participants will receive a single 0.5 mL intramuscular (IM) injection of V114 at Visit 1, 2, and 4 (approximately 3, 5, and 12 months of age). As part of the study design, participants will also receive other pediatric vaccines, including Vaxelis™ (0.5 mL single dose at Visits 1, 2, and 4); M-M-R™II (0.5 mL single dose at Visit 4); and VARIVAX™ (0.5 mL single dose at Visit 4, except participants in Norway and Denmark, who will receive a second dose of VARIVAX™ at Visit 5, according to local vaccination requirements).

Drug: V114; Drug: Vaxelis™; Drug: M-M-R®II; Drug: VARIVAX™

Prevenar 13™

ACTIVE COMPARATOR

Participants will receive a single 0.5 mL IM injection of Prevenar 13™ at Visit 1, 2, and 4 (approximately 3, 5, and 12 months of age). As part of the study design, participants will also receive other pediatric vaccines, including Vaxelis™ (0.5 mL single dose at Visits 1, 2, and 4); M-M-R™II (0.5 mL single dose at Visit 4); and VARIVAX™ (0.5 mL single dose at Visit 4, except participants in Norway and Denmark, who will receive a second dose of VARIVAX™ at Visit 5, according to local vaccination requirements).

Drug: Prevenar 13™; Drug: Vaxelis™; Drug: M-M-R®II; Drug: VARIVAX™

Interventions

V114 DRUG

15-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, 33F, serotype 6B and aluminum phosphate adjuvant in each 0.5 mL dose.

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

V114

Prevenar 13™ DRUG

13-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F, serotype 6B in each 0.5. mL dose.

Also known as: Prevnar 13™

Prevenar 13™

Vaxelis™ DRUG

Intramuscular 0.5 mL single dose

Prevenar 13™; V114

M-M-R®II DRUG

Subcutaneous 0.5 mL single dose

Also known as: Measles, Mumps, and Rubella Virus Vaccine Live

Prevenar 13™; V114

VARIVAX™ DRUG

Subcutaneous 0.5 mL single dose

Also known as: Varicella Vaccine Live

Prevenar 13™; V114

Eligibility Criteria

• Age: 70 Days - 111 Days
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Is male or female, approximately 3 months of age, from 70 days to 111 days inclusive, at the time of signing the informed consent.
• 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:

• Was born prior to 37 weeks of gestation.
• Has a history of invasive pneumococcal disease (IPD) or known history of other culture positive pneumococcal disease.
• Has a known hypersensitivity to any component of the pneumococcal conjugate vaccine (PCV), any component of the licensed pediatric vaccines to be administered concomitantly in the study, or any diphtheria toxoid containing vaccine.
• Has any contraindication to the concomitant study vaccines being administered in the study.
• Has a known or suspected impairment of immunological function.
• Has a history of congenital or acquired immunodeficiency.
• Has, or his/her mother has, a documented human immunodeficiency virus (HIV) infection.
• Has, or his/her mother has, a documented hepatitis B surface antigen - positive test.
• Has 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 a known neurologic or cognitive behavioral disorder, including encephalitis/myelitis, acute disseminating encephalomyelitis, pervasive development disorder, and related disorders.
• Has received a dose of any pneumococcal vaccine prior to study entry.
• Has received \>1 dose of monovalent hepatitis B vaccine or hepatitis B-based combination vaccine prior to study entry.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (24)

Hvidovre Hospital ( Site 0003)

Hvidovre, Capital Region, 2650, Denmark

Location

Aarhus Universitetshosp. Skejby ( Site 0002)

Aarhus, Central Jutland, 8200, Denmark

Location

Regionshospitalet Herning Hospitalsenheden Vest ( Site 0006)

Herning, Central Jutland, 7400, Denmark

Location

Aalborg Universitetshospital ( Site 0005)

Aalborg, North Denmark, 9000, Denmark

Location

Sygehus Vendsyssel Hjoerring ( Site 0004)

Hjørring, North Denmark, 9800, Denmark

Location

Odense Universitetshospital ( Site 0001)

Odense C, Region Syddanmark, 5000, Denmark

Location

Kokkolan rokotetutkimusklinikka ( Site 0029)

Kokkola, Keski-Pohjanmaa, 67100, Finland

Location

Tampereen yliopisto Oulun rokotetutkimusklinikka ( Site 0030)

Oulu, North Ostrobothnia, 90220, Finland

Location

Tampereen yliopisto - Tampereen rokotetutkimusklinikka ( Site 0021)

Tampere, Pirkanmaa, 33100, Finland

Location

Porin rokotetutkimusklinikka ( Site 0027)

Pori, Satakunta, 28100, Finland

Location

Seinajoki Vaccine Research Center ( Site 0028)

Seinäjoki, South Ostrobothnia, 60100, Finland

Location

Turun rokotetutkimuskeskus ( Site 0026)

Turku, Southwest Finland, 20520, Finland

Location

Tampereen yliopisto Espoon rokotetutkimusklinikka ( Site 0024)

Espoo, Uusimaa, 02230, Finland

Location

Tampereen yliopisto Etela-Helsingin Rokotetutkimusklinikka ( Site 0022)

Helsinki, Uusimaa, 00100, Finland

Location

Tampereen yliopisto Ita-Helsingin rokotetutkimusklinikka ( Site 0023)

Helsinki, Uusimaa, 00930, Finland

Location

Jarvenpaan rokotetutkimuskeskus ( Site 0025)

Jarvenpaa, Uusimaa, 04400, Finland

Location

Policlinico Universitario Agostino Gemelli ( Site 0048)

Rome, Roma, 00168, Italy

Location

A.O. Policlinico Consorziale di Bari ( Site 0044)

Bari, 70124, Italy

Location

A.O.U. Riuniti Di Foggia - Igiene Universitaria ( Site 0046)

Foggia, 71121, Italy

Location

IRCCS Ospedale Policlinico San Martino ( Site 0042)

Genova, 16132, Italy

Location

Stavanger universitetssykehus ( Site 0062)

Stavanger, Rogaland, 4011, Norway

Location

Sykehuset i Vestfold ( Site 0063)

Tønsberg, Vestfold, 3103, Norway

Location

Oslo Universitetssykehus HF Ulleval Sykehus ( Site 0061)

Oslo, 0450, Norway

Location

Norrlands Universitetssjukhus ( Site 0100)

Umeå, Vasterbottens Lan [se-24], 901 85, Sweden

Location

Related Publications (1)

• Benfield T, Ramet M, Valentini P, Seppa I, Dagan R, Richmond P, Mercer S, Churchill C, Lupinacci R, McFetridge R, Park J, Wittke F, Banniettis N, Musey L, Bickham K, Kaminski J. Safety, tolerability, and immunogenicity of V114 pneumococcal vaccine compared with PCV13 in a 2+1 regimen in healthy infants: A phase III study (PNEU-PED-EU-2). Vaccine. 2023 Apr 6;41(15):2456-2465. doi: 10.1016/j.vaccine.2023.02.041. Epub 2023 Feb 24.

  PMID: 36841723 RESULT

MeSH Terms

Conditions

Pneumococcal Infections

Interventions

13-valent pneumococcal vaccine; Vaxelis; Measles-Mumps-Rubella Vaccine; Chickenpox Vaccine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Vaccines, Combined; Vaccines; Biological Products; Complex Mixtures; Measles Vaccine; Viral Vaccines; Mumps Vaccine; Rubella Vaccine; Herpesvirus Vaccines

Results Point of Contact

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

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical 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: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2019
• First Posted: July 11, 2019
• Study Start: August 28, 2019
• Primary Completion: October 29, 2021
• Study Completion: October 29, 2021
• Last Updated: May 6, 2023
• Results First Posted: December 1, 2022

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will share

Locations

SE (1); FI (10); IT (4); DK (6); NO (3)