Clinical trial NCT04031846: Safety, Tolerability, and Immunogenicity of V114 in Healthy Infants (V114-025)
Official title: A Phase 3, Multicenter, Randomized, Double-blind, Active-comparator-controlled Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 in Healthy Infants (PNEU-PED-EU-1)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pneumococcal Infections
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2019-07-24
Enrollment: 1184
Sex: ALL
Minimum age (years): 42
Maximum age (years): 90
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study will evaluate the safety and tolerability and immunogenicity of V114 when administered to 2-month old infants. The primary hypotheses are: 1) V114 is non-inferior to Prevenar 13™ for the 13 shared serotypes between V114 and Prevenar 13™ based on response rates at 30 days post toddler dose (PTD); 2) V114 is superior to Prevenar 13™ for the 2 serotypes unique to V114 based on the response rates at 30 days PTD; 3) V114 is non-inferior to Prevenar 13™ for the 13 shared serotypes between V114 and Prevenar 13™ based on anti-pneumococcal polysaccharide (PnPs) serotype-specific Immunoglobin G (IgG) geometric mean concentrations (GMCs) at 30 days PTD; and 4) V114 is superior to Prevenar 13™ for the 2 serotypes unique to V114 based on anti-PnPs serotype-specific IgG GMCs at 30 days PTD.


Eligibility criteria: Inclusion Criteria

* Healthy
* 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

* History of invasive pneumococcal disease \[(IPD); positive blood culture, positive cerebrospinal fluid culture, or other sterile site\] or known history of other culture positive pneumococcal disease
* 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 influenzae type b conjugate vaccine, poliovirus vaccine, rotavirus 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
* Is or has an immediate family member (eg, parent/legal guardian or sibling) who is investigational site or Sponsor staff directly involved with this study

Primary outcomes:
measure: Percentage of Participants That Report at Least 1 Solicited Injection-site Adverse Event (AE)
timeFrame: Up to 14 days post any vaccination (up to approximately study month 13)
measure: Percentage of Participants That Report at Least 1 Solicited Systemic AE
timeFrame: Up to 14 days post any vaccination (up to approximately study month 13)
measure: Percentage of Participants That Report at Least 1 Vaccine-related Serious Adverse Event (SAE)
timeFrame: Up to 6 months post last vaccination (up to approximately study month 20)
measure: Anti-pneumococcal Polysaccharide (PnPs) Serotype-specific Immunoglobin G (IgG) Geometric Mean Concentrations (GMC) for Each Serotype at 30 Days Post Toddler Dose (PTD)
timeFrame: 30 days PTD (Up to approximately study month 14)
measure: Percentage of Participants Who Meet Serotype-specific IgG Threshold Value of ≥0.35 μg/mL for Each Serotype at 30 Days PTD
timeFrame: 30 days PTD (Up to approximately study month 14)
Secondary outcomes:
measure: Percentage of Participants Who Meet Antigen-Specific Threshold Value for Each Antigen in Infanrix™ Hexa at 30 Days PTD
timeFrame: 30 days PTD (Up to approximately study month 14)
measure: Anti-rotavirus Immunoglobulin A (IgA) Geometric Mean Titers (GMTs) at 30 Days Post Primary Series (PPS) of Rotarix™
timeFrame: 30 days PPS (Up to approximately study month 3)
measure: Anti-PnPs Serotype-specific IgG GMCs for Each Serotype at 30 Days PPS
timeFrame: 30 days PPS (Up to approximately study month 3)
measure: Percentage of Participants Who Meet Serotype-specific IgG Threshold Value of ≥0.35 μg/mL for Each Serotype at 30 Days PPS
timeFrame: 30 days PPS (Up to approximately study month 3)
measure: Anti-PnPs Serotype-specific Opsonophagocytic Activity (OPA) GMTs for Each Serotype at 30 Days PTD
timeFrame: 30 days PTD (Up to approximately study month 14)
measure: Percentage of Participants Who Meet Serotype-specific OPA Threshold Value for Each Serotype at 30 Days PTD
timeFrame: 30 days PTD (Up to approximately study month 14)
measure: Percentage of Participants Who Achieved the IgG Serotype-Specific Threshold Value of ≥0.35 μg/mL For Protocol Pre-Specified Serotypes at 30 Days PTD
timeFrame: 30 days PTD (Up to approximately study month 14)
Other outcomes:
Locations:
city: South Brisbane
country: Australia
facility: Queensland Children s Hospital ( Site 0004)
state: Queensland
city: Melbourne
country: Australia
facility: Vaccine and Immunisation Research Group - VIRGo ( Site 0002)
state: Victoria
city: Nedlands
country: Australia
facility: Telethon Kids Institute ( Site 0003)
city: Aalst
country: Belgium
facility: O.L.V. Ziekenhuis Aalst ( Site 0144)
city: Brugge
country: Belgium
facility: AZ Sint Jan Brugge-Oostende ( Site 0147)
city: Gent
country: Belgium
facility: AZ Maria Middelares Gent ( Site 0142)
city: Gent
country: Belgium
facility: UZ Gent ( Site 0141)
city: Oostende
country: Belgium
facility: AZ Henry Serruys ( Site 0148)
city: Roeselare
country: Belgium
facility: AZ Delta ( Site 0143)
city: Jindrichuv Hradec
country: Czechia
facility: MUDr. Daniel Drazan - Prakticky lekar pro deti a dorost ( Site 0151)
city: Melnik
country: Czechia
facility: MU Dr. Jan Nemecek - Prakticky lekar pro deti a dorost ( Site 0152)
city: Tynec nad Sazavou
country: Czechia
facility: MUDr. Josef Zemanek ( Site 0153)
city: Paide
country: Estonia
facility: Vee Perearstikeskus ( Site 0163)
state: Jarvamaa
city: Tallinn
country: Estonia
facility: Merekivi Perearstid ( Site 0165)
city: Tallinn
country: Estonia
facility: Merelahe Perearstikeskus OU ( Site 0164)
city: Tallinn
country: Estonia
facility: Sinu Arst Tervisekeskus ( Site 0167)
city: Tallinn
country: Estonia
facility: Rosenthali Perearstikeskus OU ( Site 0166)
city: Tartu
country: Estonia
facility: Kliiniliste Uuringute Keskus OU ( Site 0161)
city: Aschaffenburg
country: Germany
facility: NETSTAP - Sandner ( Site 0072)
city: Bramsche
country: Germany
facility: Kinderarztpraxis ( Site 0061)
city: Datteln
country: Germany
facility: Praxis Dr. Schmute ( Site 0078)
city: Erfurt
country: Germany
facility: Praxis fur Kinder und Jugendmedizin Eivy Franke Beckmann ( Site 0064)
city: Hamburg
country: Germany
facility: Kinderarztpraxis Dr. Friedrich Kaiser & Dr. Marinesse ( Site 0065)
city: Herxheim
country: Germany
facility: Kinderarztpraxis Dr. Juenger ( Site 0073)
city: Huerth
country: Germany
facility: Kinderpraxis Dr. med. Andreas Petri ( Site 0066)
city: Moenchengladbach
country: Germany
facility: Kinderarztpraxis ( Site 0068)
city: Oberhausen
country: Germany
facility: Kinder- und Jugendaerztliche Gemeinschaftspraxis ( Site 0077)
city: Schoenau
country: Germany
facility: Praxiszentrum Triftplatz ( Site 0075)
city: Schweigen
country: Germany
facility: Praxis Dr. Siegfried Simmet ( Site 0069)
city: Tauberbischofsheim
country: Germany
facility: Kinderarztpraxis Dr. Rolf Ebert & Dr. Matthias Huebener ( Site 0062)
city: Wolfsburg
country: Germany
facility: Kinderaerztliche Gemeinschaftspraxis Drs. Westerholt/Matyas ( Site 0074)
city: Wuerselen
country: Germany
facility: Kinderarztpraxis ( Site 0063)
city: Athens
country: Greece
facility: Pan and Aglaia Kyriakou Children s Hospital ( Site 0183)
city: Athens
country: Greece
facility: University of Athens - Aghia Sophia Childrens Hospital ( Site 0185)
city: Athens
country: Greece
facility: Attikon University General Hospital of Athens ( Site 0182)
city: Larissa
country: Greece
facility: University General Hospital of Larissa ( Site 0184)
city: Thessaloniki
country: Greece
facility: Hippokration General Hospital of Thessaloniki ( Site 0181)
city: Bydgoszcz
country: Poland
facility: Centrum Medyczne Pratia Bydgoszcz ( Site 0086)
city: Debica
country: Poland
facility: Prywatny Gabinet Lekarski Dr med Jerzy Brzostek ( Site 0084)
city: Krakow
country: Poland
facility: Krakowski Szpital Specjalistyczny im. Jana Pawla II ( Site 0085)
city: Lodz
country: Poland
facility: Gravita Diagnostyka i Leczenie Nieplodnosci ( Site 0092)
city: Lomianki
country: Poland
facility: SPZOZ im. Dzieci Warszawy w Dziekanowie Lesnym ( Site 0091)
city: Poznan
country: Poland
facility: SPZOZ Szpital Dzieciecy Poznan ( Site 0089)
city: Siemianowice Slaskie
country: Poland
facility: NZ Lecznictwa Ambulatoryjnego - Michalkowice - Jarosz i Partnerzy ( Site 0087)
city: Trzebnica
country: Poland
facility: Szpital im. sw. Jadwigi Slaskiej w Trzebnicy ( Site 0083)
city: Wroclaw
country: Poland
facility: Uniwersytecki Szpital Kliniczny ( Site 0093)
city: Ekaterinburg
country: Russian Federation
facility: MAI Childrens City Clinical Hospital 11 ( Site 0047)
city: Moscow
country: Russian Federation
facility: Central Clinical Hospital of Russian Academy Science ( Site 0052)
city: St.Petersburg
country: Russian Federation
facility: Children s City Polyclinic No. 45 of the Nevsky District ( Site 0048)
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol ( Site 0102)
state: Barcelona
city: Antequera
country: Spain
facility: Hospital de Antequera ( Site 0111)
state: Malaga
city: Paiporta
country: Spain
facility: Centro de Salud Paiporta ( Site 0117)
state: Valencia
city: Quart de Poblet
country: Spain
facility: C.S. Quart de Poblet ( Site 0115)
state: Valencia
city: Madrid
country: Spain
facility: Hospital General Universitario 12 de Octubre ( Site 0106)
city: Madrid
country: Spain
facility: Hospital Universitario La Paz ( Site 0107)
city: Madrid
country: Spain
facility: Hospital Sanitas La Moraleja ( Site 0103)
city: Santiago de Compostela
country: Spain
facility: Hospital Clinico Universitario de Santiago ( Site 0109)
city: Sevilla
country: Spain
facility: Unidad de Estudios e Investigacion IHP ( Site 0101)
city: Valencia
country: Spain
facility: C.S. Serreria II ( Site 0116)
city: Valencia
country: Spain
facility: Centro de Salud Eliana ( Site 0114)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Martinon-Torres F, Wysocki J, Szenborn L, Carmona-Martinez A, Poder A, Dagan R, Richmond P, Gilbert C, Trudel MC, Flores S, Lupinacci R, McFetridge R, Wiedmann RT, Chen Q, Gerrits H, Banniettis N, Musey L, Bickham K, Kaminski J; V114-025 PNEU-PED-EU-1 study group. A Phase III, multicenter, randomized, double-blind, active comparator-controlled study to evaluate the safety, tolerability, and immunogenicity of V114 compared with PCV13 in healthy infants (PNEU-PED-EU-1). Vaccine. 2023 May 16;41(21):3387-3398. doi: 10.1016/j.vaccine.2023.04.036. Epub 2023 Apr 25.