Clinical trial NCT04016714: Safety, Tolerability, and Immunogenicity of a 3-dose Regimen of V114 in Healthy Infants (PNEU-PED-EU-2/V114-026)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pneumococcal Infections
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2019-07-11
Enrollment: 1191
Sex: ALL
Minimum age (years): 70
Maximum age (years): 111
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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™.


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.

Primary outcomes:
measure: Percentage of Participants With a Solicited Injection-site Adverse Event
timeFrame: Day 1 to Day 14 after each vaccination
measure: Percentage of Participants With a Solicited Systemic Adverse Event
timeFrame: Day 1 to Day 14 after each vaccination
measure: Percentage of Participants With a Vaccine-related Serious Adverse Event
timeFrame: Up to approximately 6 months after Dose 3 (up to approximately 16 months)
measure: Percentage of Participants Meeting Serotype-specific Immunoglobulin G (IgG) Threshold Value of ≥0.35 μg/mL 30 Days After Dose 3
timeFrame: 30 days after Dose 3
measure: Geometric Mean Concentration (GMC) of Serotype-specific Immunoglobulin G (IgG) 30 Days After Dose 3
timeFrame: 30 days after Dose 3
Secondary outcomes:
measure: Percentage of Participants Meeting Specified Vaxelis™ Antigen Reponses 30 Days After Dose 3
timeFrame: 30 days after Dose 3
measure: Percentage of Participants Meeting Serotype-specific IgG Threshold Value of ≥0.35 μg/mL 30 Days After Dose 2
timeFrame: 30 days after Dose 2
measure: GMC of Serotype-specific IgG 30 Days After Dose 2
timeFrame: 30 days after Dose 2
measure: Percentage of Participants Meeting Specified Opsonophagocytic Activity (OPA) Responses 30 Days After Dose 3
timeFrame: 30 days after Dose 3
measure: Geometric Mean Titers (GMTs) of Serotype-specific OPA 30 Days After Dose 3
timeFrame: 30 days after Dose 3
Other outcomes:
Locations:
city: Hvidovre
country: Denmark
facility: Hvidovre Hospital ( Site 0003)
state: Hovedstaden
city: Aarhus
country: Denmark
facility: Aarhus Universitetshosp. Skejby ( Site 0002)
state: Midtjylland
city: Herning
country: Denmark
facility: Regionshospitalet Herning Hospitalsenheden Vest ( Site 0006)
state: Midtjylland
city: Aalborg
country: Denmark
facility: Aalborg Universitetshospital ( Site 0005)
state: Nordjylland
city: Hjoerring
country: Denmark
facility: Sygehus Vendsyssel Hjoerring ( Site 0004)
state: Nordjylland
city: Odense C
country: Denmark
facility: Odense Universitetshospital ( Site 0001)
state: Syddanmark
city: Kokkola
country: Finland
facility: Kokkolan rokotetutkimusklinikka ( Site 0029)
state: Mellersta Osterbotten
city: Tampere
country: Finland
facility: Tampereen yliopisto - Tampereen rokotetutkimusklinikka ( Site 0021)
state: Pirkanmaa
city: Oulu
country: Finland
facility: Tampereen yliopisto Oulun rokotetutkimusklinikka ( Site 0030)
state: Pohjois-Pohjanmaa
city: Pori
country: Finland
facility: Porin rokotetutkimusklinikka ( Site 0027)
state: Satakunta
city: Seinajoki
country: Finland
facility: Seinajoki Vaccine Research Center ( Site 0028)
state: Sodra Osterbotten
city: Espoo
country: Finland
facility: Tampereen yliopisto Espoon rokotetutkimusklinikka ( Site 0024)
state: Uusimaa
city: Helsinki
country: Finland
facility: Tampereen yliopisto Etela-Helsingin Rokotetutkimusklinikka ( Site 0022)
state: Uusimaa
city: Helsinki
country: Finland
facility: Tampereen yliopisto Ita-Helsingin rokotetutkimusklinikka ( Site 0023)
state: Uusimaa
city: Jarvenpaa
country: Finland
facility: Jarvenpaan rokotetutkimuskeskus ( Site 0025)
state: Uusimaa
city: Turku
country: Finland
facility: Turun rokotetutkimuskeskus ( Site 0026)
state: Varsinais-Suomi
city: Rome
country: Italy
facility: Policlinico Universitario Agostino Gemelli ( Site 0048)
state: Roma
city: Bari
country: Italy
facility: A.O. Policlinico Consorziale di Bari ( Site 0044)
city: Foggia
country: Italy
facility: A.O.U. Riuniti Di Foggia - Igiene Universitaria ( Site 0046)
city: Genova
country: Italy
facility: IRCCS Ospedale Policlinico San Martino ( Site 0042)
city: Stavanger
country: Norway
facility: Stavanger universitetssykehus ( Site 0062)
state: Rogaland
city: Toensberg
country: Norway
facility: Sykehuset i Vestfold ( Site 0063)
state: Vestfold
city: Oslo
country: Norway
facility: Oslo Universitetssykehus HF Ulleval Sykehus ( Site 0061)
city: Umea
country: Sweden
facility: Norrlands Universitetssjukhus ( Site 0100)
state: Vasterbottens Lan [se-24]
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.