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

NCT ID: NCT04016714

Last Updated: 2023-05-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1191 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-28
• Study Completion Date: 2021-10-29

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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).

Group Type: EXPERIMENTAL

V114

Intervention Type: 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.

Vaxelis™

Intervention Type: DRUG

Intramuscular 0.5 mL single dose

M-M-R®II

Intervention Type: DRUG

Subcutaneous 0.5 mL single dose

VARIVAX™

Intervention Type: DRUG

Subcutaneous 0.5 mL single dose

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).

Group Type: ACTIVE_COMPARATOR

Prevenar 13™

Intervention Type: 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.

Vaxelis™

Intervention Type: DRUG

Intramuscular 0.5 mL single dose

M-M-R®II

Intervention Type: DRUG

Subcutaneous 0.5 mL single dose

VARIVAX™

Intervention Type: DRUG

Subcutaneous 0.5 mL single dose

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Vaxelis™

Intramuscular 0.5 mL single dose

Intervention Type: DRUG

M-M-R®II

Subcutaneous 0.5 mL single dose

Intervention Type: DRUG

VARIVAX™

Subcutaneous 0.5 mL single dose

Intervention Type: DRUG

Other Intervention Names

VAXNEUVANCE™; Pneumococcal 15-Valent Conjugate Vaccine; Prevnar 13™; Measles, Mumps, and Rubella Virus Vaccine Live; Varicella Vaccine Live

Eligibility Criteria

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.

• Minimum Eligible Age: 70 Days
• Maximum Eligible Age: 111 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

Hvidovre Hospital ( Site 0003)

Hvidovre, Capital Region, Denmark

Aarhus Universitetshosp. Skejby ( Site 0002)

Aarhus, Central Jutland, Denmark

Regionshospitalet Herning Hospitalsenheden Vest ( Site 0006)

Herning, Central Jutland, Denmark

Aalborg Universitetshospital ( Site 0005)

Aalborg, North Denmark, Denmark

Sygehus Vendsyssel Hjoerring ( Site 0004)

Hjørring, North Denmark, Denmark

Odense Universitetshospital ( Site 0001)

Odense C, Region Syddanmark, Denmark

Kokkolan rokotetutkimusklinikka ( Site 0029)

Kokkola, Keski-Pohjanmaa, Finland

Tampereen yliopisto Oulun rokotetutkimusklinikka ( Site 0030)

Oulu, North Ostrobothnia, Finland

Tampereen yliopisto - Tampereen rokotetutkimusklinikka ( Site 0021)

Tampere, Pirkanmaa, Finland

Porin rokotetutkimusklinikka ( Site 0027)

Pori, Satakunta, Finland

Seinajoki Vaccine Research Center ( Site 0028)

Seinäjoki, South Ostrobothnia, Finland

Turun rokotetutkimuskeskus ( Site 0026)

Turku, Southwest Finland, Finland

Tampereen yliopisto Espoon rokotetutkimusklinikka ( Site 0024)

Espoo, Uusimaa, Finland

Tampereen yliopisto Etela-Helsingin Rokotetutkimusklinikka ( Site 0022)

Helsinki, Uusimaa, Finland

Tampereen yliopisto Ita-Helsingin rokotetutkimusklinikka ( Site 0023)

Helsinki, Uusimaa, Finland

Jarvenpaan rokotetutkimuskeskus ( Site 0025)

Järvenpää, Uusimaa, Finland

Policlinico Universitario Agostino Gemelli ( Site 0048)

Rome, Roma, Italy

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

Bari, , Italy

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

Foggia, , Italy

IRCCS Ospedale Policlinico San Martino ( Site 0042)

Genova, , Italy

Stavanger universitetssykehus ( Site 0062)

Stavanger, Rogaland, Norway

Sykehuset i Vestfold ( Site 0063)

Tønsberg, Vestfold, Norway

Oslo Universitetssykehus HF Ulleval Sykehus ( Site 0061)

Oslo, , Norway

Norrlands Universitetssjukhus ( Site 0100)

Umeå, Vasterbottens Lan [se-24], Sweden

Countries

Denmark; Finland; Italy; Norway; Sweden

References

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.

Reference Type: RESULT

PMID: 36841723 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

V114-026

Identifier Type: OTHER

Identifier Source: secondary_id

2018-003788-70

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

V114-026

Identifier Type: -

Identifier Source: org_study_id