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

A Phase 3, Multicenter, Randomized, Double-blind, Active-comparator-controlled Study to Evaluate the Safety, Tolerability, and Immunogenicity of a 3-dose Regimen of V114 in Healthy Infants (PNEU-PED-EU-2)

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™.

Study Overview

• Status: Completed
• Conditions: Pneumococcal Infections
• Intervention / Treatment: Drug: V114; Drug: Vaxelis™; Drug: M-M-R®II; Drug: VARIVAX™; Drug: Prevenar 13™

• Study Type: Interventional
• Enrollment (Actual): 1191
• Phase: Phase 3

Contacts and Locations

Study Locations

• Denmark
  • Hovedstaden
    • Hvidovre, Hovedstaden, Denmark, 2650
      • Hvidovre Hospital ( Site 0003)
  • Midtjylland
    • Aarhus, Midtjylland, Denmark, 8200
      • Aarhus Universitetshosp. Skejby ( Site 0002)
    • Herning, Midtjylland, Denmark, 7400
      • Regionshospitalet Herning Hospitalsenheden Vest ( Site 0006)
  • Nordjylland
    • Aalborg, Nordjylland, Denmark, 9000
      • Aalborg Universitetshospital ( Site 0005)
    • Hjoerring, Nordjylland, Denmark, 9800
      • Sygehus Vendsyssel Hjoerring ( Site 0004)
  • Syddanmark
    • Odense C, Syddanmark, Denmark, 5000
      • Odense Universitetshospital ( Site 0001)
• Finland
  • Mellersta Osterbotten
    • Kokkola, Mellersta Osterbotten, Finland, 67100
      • Kokkolan rokotetutkimusklinikka ( Site 0029)
  • Pirkanmaa
    • Tampere, Pirkanmaa, Finland, 33100
      • Tampereen yliopisto - Tampereen rokotetutkimusklinikka ( Site 0021)
  • Pohjois-Pohjanmaa
    • Oulu, Pohjois-Pohjanmaa, Finland, 90220
      • Tampereen yliopisto Oulun rokotetutkimusklinikka ( Site 0030)
  • Satakunta
    • Pori, Satakunta, Finland, 28100
      • Porin rokotetutkimusklinikka ( Site 0027)
  • Sodra Osterbotten
    • Seinajoki, Sodra Osterbotten, Finland, 60100
      • Seinajoki Vaccine Research Center ( Site 0028)
  • Uusimaa
    • Espoo, Uusimaa, Finland, 02230
      • Tampereen yliopisto Espoon rokotetutkimusklinikka ( Site 0024)
    • Helsinki, Uusimaa, Finland, 00100
      • Tampereen yliopisto Etela-Helsingin Rokotetutkimusklinikka ( Site 0022)
    • Helsinki, Uusimaa, Finland, 00930
      • Tampereen yliopisto Ita-Helsingin rokotetutkimusklinikka ( Site 0023)
    • Jarvenpaa, Uusimaa, Finland, 04400
      • Jarvenpaan rokotetutkimuskeskus ( Site 0025)
  • Varsinais-Suomi
    • Turku, Varsinais-Suomi, Finland, 20520
      • Turun rokotetutkimuskeskus ( Site 0026)
• Italy
  • Bari, Italy, 70124
    • A.O. Policlinico Consorziale di Bari ( Site 0044)
  • Foggia, Italy, 71121
    • A.O.U. Riuniti Di Foggia - Igiene Universitaria ( Site 0046)
  • Genova, Italy, 16132
    • IRCCS Ospedale Policlinico San Martino ( Site 0042)
  • Roma
    • Rome, Roma, Italy, 00168
      • Policlinico Universitario Agostino Gemelli ( Site 0048)
• Norway
  • Oslo, Norway, 0450
    • Oslo Universitetssykehus HF Ulleval Sykehus ( Site 0061)
  • Rogaland
    • Stavanger, Rogaland, Norway, 4011
      • Stavanger universitetssykehus ( Site 0062)
  • Vestfold
    • Toensberg, Vestfold, Norway, 3103
      • Sykehuset i Vestfold ( Site 0063)
• Sweden
  • Vasterbottens Lan [se-24]
    • Umea, Vasterbottens Lan [se-24], Sweden, 901 85
      • Norrlands Universitetssjukhus ( Site 0100)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 1 year (Child)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.
• Has received a dose of any acellular pertussis- or whole cell pertussis-based combination vaccines, Haemophilus influenza type b conjugate vaccine, poliovirus vaccine, or any other combination thereof, prior to study entry.
• Has received a blood transfusion or blood products, including immunoglobulins.
• Has participated in another clinical study of an investigational product before the beginning or anytime during the duration of the current clinical study. Participants enrolled in observational studies may be included; these will be reviewed on a case by-case basis for approval by the Sponsor.
• Has any other reason that, in the opinion of the investigator, may interfere with the evaluation required by the study. Reasons may include, but are not limited to, being unable to keep appointments or planning to relocate during the study.
• Is or has an immediate family member (e.g., parent/legal guardian or sibling) who is investigational site or Sponsor staff directly involved with this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: V114; 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; 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.; Other Names: VAXNEUVANCE™; Pneumococcal 15-Valent Conjugate Vaccine; Drug: Vaxelis™; Intramuscular 0.5 mL single dose; Drug: M-M-R®II; Subcutaneous 0.5 mL single dose; Other Names: Measles, Mumps, and Rubella Virus Vaccine Live; Drug: VARIVAX™; Subcutaneous 0.5 mL single dose; Other Names: Varicella Vaccine Live
Active Comparator: Prevenar 13™; 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: Vaxelis™; Intramuscular 0.5 mL single dose; Drug: M-M-R®II; Subcutaneous 0.5 mL single dose; Other Names: Measles, Mumps, and Rubella Virus Vaccine Live; Drug: VARIVAX™; Subcutaneous 0.5 mL single dose; Other Names: Varicella Vaccine Live; Drug: Prevenar 13™; 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.; Other Names: Prevnar 13™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Meeting Specified Vaxelis™ Antigen Reponses 30 Days After Dose 3	Antigen-specific response rates in participants administered V114 concomitantly with Vaxelis™ were compared with response rates in participants administered Prevenar 13™ concomitantly with Vaxelis™, and the percentages of participants meeting specified Vaxelis™ antigen responses recorded. Antigens in Vaxelis™ include: diphtheria toxoid, tetanus toxoid, pertussis toxin (PT), pertussis filamentous hemagglutinin (FHA), pertussis fimbriae 2/3 (FIM 2/3), pertussis pertactin (PRN), Haemophilus influenzae type b polyribosylribitol phosphate (Hib-PRP), hepatitis B surface antigen (HBsAg), and poliovirus serotypes 1, 2, and 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	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 ECL assay. Immunoglobulin G for the 15 serotypes contained in V114 vaccine was determined using a PnECL assay.	30 days after Dose 2
GMC of Serotype-specific IgG 30 Days After Dose 2	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 ECL assay. Immunoglobulin G for the 15 serotypes contained in V114 vaccine was determined using a PnECL assay.	30 days after Dose 2
Percentage of Participants Meeting Specified Opsonophagocytic Activity (OPA) Responses 30 Days After Dose 3	OPA for 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 unique to V114 (22F and 33F) was measured using a multiplex opsonophagocytic assay (MOPA).	30 days after Dose 3
Geometric Mean Titers (GMTs) of Serotype-specific OPA 30 Days After Dose 3	Sera from participants was used to measure GMT of 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 unique to V114 (22F and 33F) was determined using a MOPA.	30 days after Dose 3

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2019
• Primary Completion (Actual): October 29, 2021
• Study Completion (Actual): October 29, 2021

Study Registration Dates

• First Submitted: July 10, 2019
• First Submitted That Met QC Criteria: July 10, 2019
• First Posted (Actual): July 11, 2019

Study Record Updates

• Last Update Posted (Estimate): May 4, 2023
• Last Update Submitted That Met QC Criteria: May 2, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Streptococcal Infections; Gram-Positive Bacterial Infections; Pneumococcal Infections; Physiological Effects of Drugs; Immunologic Factors; Vaccines; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: V114-026 (Other Identifier: Merck Protocol Number); 2018-003788-70 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes