Safety, Tolerability, and Immunogenicity of V114 in Healthy Infants (V114-025)

NCT04031846 | Completed Phase 3 Results DMC

• 2 other identifiers: V114-0252018-003787-31
• Study Type: interventional
• Target: 1,184
• Locations: 8 countries
• Sites: 54

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.

Conditions

Pneumococcal Infections

Outcome Measures

Primary Outcomes (5)

• Percentage of Participants That Report at Least 1 Solicited Injection-site Adverse Event (AE)

  An AE is any untoward medical occurrence in a participant temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease (new or exacerbated) temporally associated with the use of a study intervention. Injection-site AEs solicited on the Vaccine Report Card (VRC) consisted of erythema (redness), induration (hard lump), pain (tenderness) and swelling.

  Up to 14 days post any vaccination (up to approximately study month 13)

• Percentage of Participants That Report at Least 1 Solicited Systemic AE

  An AE is any untoward medical occurrence in a participant temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease (new or exacerbated) temporally associated with the use of a study intervention. Systemic AEs solicited on the VRC consisted of decreased appetite (loss of appetite), irritability, somnolence (drowsiness) and urticaria (hive/welts).

  Up to 14 days post any vaccination (up to approximately study month 13)

• Percentage of Participants That Report at Least 1 Vaccine-related Serious Adverse Event (SAE)

  A serious adverse event (SAE) is an AE that results in death, is life threatening, results in a persistent or significant disability or incapacity, results in or prolongs an existing hospitalization, is a congenital anomaly or birth defect, is a cancer, is an overdose, or is another important medical event. The relatedness of a vaccine to a SAE is determined by an investigator who is a qualified physician.

  Up to 6 months post last vaccination (up to approximately study month 20)

• Anti-pneumococcal Polysaccharide (PnPs) Serotype-specific Immunoglobin G (IgG) Geometric Mean Concentrations (GMC) for Each Serotype at 30 Days Post Toddler Dose (PTD)

  Sera from participants was used to measure vaccine-induced anti-PnPs serotype-specific IgG for each serotype using pneumococcal electrochemiluminescence (PnECL). The Geometric Mean Concentration (GMC) for each of the 13 serotypes shared by both V114 and Prevenar 13™ (Serotypes 1 to 23F); and the 2 serotypes unique to V114 (Serotypes 22F and 33F) was assessed. Per protocol, within-group CIs were not calculated.

  30 days PTD (Up to approximately study month 14)

• Percentage of Participants Who Meet Serotype-specific IgG Threshold Value of ≥0.35 μg/mL for Each Serotype at 30 Days PTD

  Sera from participants was used to measure vaccine-induced anti-PnPs serotype-specific IgG for the 15 serotypes using pneumococcal electrochemiluminescence (PnECL). The percentage of participants that achieve the threshold value of ≥0.35 μg/mL for each of the 13 serotypes shared by both V114 and Prevenar 13™ (Serotypes 1 to 23F); and the 2 serotypes unique to V114 (Serotypes 22F and 33F) was assessed.

  30 days PTD (Up to approximately study month 14)

Secondary Outcomes (7)

• Percentage of Participants Who Meet Antigen-Specific Threshold Value for Each Antigen in Infanrix™ Hexa at 30 Days PTD

  30 days PTD (Up to approximately study month 14)

• Anti-rotavirus Immunoglobulin A (IgA) Geometric Mean Titers (GMTs) at 30 Days Post Primary Series (PPS) of Rotarix™

  30 days PPS (Up to approximately study month 3)

• Anti-PnPs Serotype-specific IgG GMCs for Each Serotype at 30 Days PPS

  30 days PPS (Up to approximately study month 3)

• Percentage of Participants Who Meet Serotype-specific IgG Threshold Value of ≥0.35 μg/mL for Each Serotype at 30 Days PPS

  30 days PPS (Up to approximately study month 3)

• Anti-PnPs Serotype-specific Opsonophagocytic Activity (OPA) GMTs for Each Serotype at 30 Days PTD

  30 days PTD (Up to approximately study month 14)

Study Arms (2)

V114

EXPERIMENTAL

Full-term infants received a 0.5 mL intramuscular injection of V114 at approximately 2, 4, and 11-15 months of age (Study Day 1, Month 2, and Month 9-13). Preterm infants received a 0.5 mL intramuscular injection of V114 at approximately 2, 3, 4, and 11-15 months of age (Study Day 1, Month 1, Month 2, and Month 9-13). All infants also received intramuscular injection of 0.5 mL Infanrix™ hexa at approximately 2, 3, 4, and 11-15 months of age and 1.5 mL oral dose of Rotarix™ at 2 and 4 months of age.

Drug: Rotarix™; Drug: Infanrix™ hexa; Drug: V114

Prevenar 13™

ACTIVE COMPARATOR

Full-term infants received a 0.5 mL intramuscular injection of Prevenar 13™ at approximately 2, 4, and 11-15 months of age (Study Day 1, Month 2, and Month 9-13). Preterm infants received a 0.5 mL intramuscular injection of Prevenar 13™ at approximately 2, 3, 4, and 11-15 months of age (Study Day 1, Month 1, Month 2, and Month 9-13). All infants also received intramuscular injection of 0.5 mL Infanrix™ hexa at approximately 2, 3, 4, and 11-15 months of age and 1.5 mL oral dose of Rotarix™ at 2 and 4 months of age.

Drug: Rotarix™; Drug: Infanrix™ hexa; Drug: Prevenar 13™

Interventions

Rotarix™ DRUG

Single 1.5 mL oral dose at 2 and 4 months of age (Study Day 1 and Month 2)

Prevenar 13™; V114

Infanrix™ hexa DRUG

Single 0.5 mL intramuscular injection at 2, 3, 4, and 11-15 months of age (Study Day 1, Month 1, Month 2, and Month 9-13)

Prevenar 13™; V114

V114 DRUG

15-valent pneumococcal conjugate vaccine (PCV) containing 13 serotypes present in Prevenar 13™ (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) and 2 unique serotypes (22F and 33F) in each 0.5 mL intramuscular administration,

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

V114

Prevenar 13™ DRUG

13-valent PCV containing 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) in each 0.5 mL intramuscular administration.

Prevenar 13™

Eligibility Criteria

• Age: 42 Days - 90 Days
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (60)

Queensland Children s Hospital ( Site 0004)

South Brisbane, Queensland, 4101, Australia

Location

Vaccine and Immunisation Research Group - VIRGo ( Site 0002)

Melbourne, Victoria, 3010, Australia

Location

Telethon Kids Institute ( Site 0003)

Nedlands, 6009, Australia

Location

O.L.V. Ziekenhuis Aalst ( Site 0144)

Aalst, 9300, Belgium

Location

AZ Sint Jan Brugge-Oostende ( Site 0147)

Bruges, 8000, Belgium

Location

AZ Maria Middelares Gent ( Site 0142)

Ghent, 9000, Belgium

Location

UZ Gent ( Site 0141)

Ghent, 9000, Belgium

Location

AZ Henry Serruys ( Site 0148)

Ostend, 8400, Belgium

Location

AZ Delta ( Site 0143)

Roeselare, 8800, Belgium

Location

MUDr. Daniel Drazan - Prakticky lekar pro deti a dorost ( Site 0151)

Jindřichův Hradec, 377 01, Czechia

Location

MU Dr. Jan Nemecek - Prakticky lekar pro deti a dorost ( Site 0152)

Mělník, 276 01, Czechia

Location

MUDr. Josef Zemanek ( Site 0153)

Týnec nad Sázavou, 257 41, Czechia

Location

Vee Perearstikeskus ( Site 0163)

Paide, Järvamaa, 72713, Estonia

Location

Merekivi Perearstid ( Site 0165)

Tallinn, 10617, Estonia

Location

Merelahe Perearstikeskus OU ( Site 0164)

Tallinn, 10617, Estonia

Location

Sinu Arst Tervisekeskus ( Site 0167)

Tallinn, 11313, Estonia

Location

Rosenthali Perearstikeskus OU ( Site 0166)

Tallinn, 11315, Estonia

Location

Kliiniliste Uuringute Keskus OU ( Site 0161)

Tartu, 50160, Estonia

Location

NETSTAP - Sandner ( Site 0072)

Aschaffenburg, 63739, Germany

Location

Kinderarztpraxis ( Site 0061)

Bramsche, 49565, Germany

Location

Praxis Dr. Schmute ( Site 0078)

Datteln, 45711, Germany

Location

Praxis fur Kinder und Jugendmedizin Eivy Franke Beckmann ( Site 0064)

Erfurt, 99086, Germany

Location

Kinderarztpraxis Dr. Friedrich Kaiser & Dr. Marinesse ( Site 0065)

Hamburg, 22415, Germany

Location

Kinderarztpraxis Dr. Juenger ( Site 0073)

Herxheim, 76863, Germany

Location

Kinderpraxis Dr. med. Andreas Petri ( Site 0066)

Hürth, 50354, Germany

Location

Kinderarztpraxis ( Site 0068)

Mönchengladbach, 41236, Germany

Location

Kinder- und Jugendaerztliche Gemeinschaftspraxis ( Site 0077)

Oberhausen, 46145, Germany

Location

Praxiszentrum Triftplatz ( Site 0075)

Schönau, 83471, Germany

Location

Praxis Dr. Siegfried Simmet ( Site 0069)

Schweigen, 76889, Germany

Location

Kinderarztpraxis Dr. Rolf Ebert & Dr. Matthias Huebener ( Site 0062)

Tauberbischofsheim, 97941, Germany

Location

Kinderaerztliche Gemeinschaftspraxis Drs. Westerholt/Matyas ( Site 0074)

Wolfsburg, 38448, Germany

Location

Kinderarztpraxis ( Site 0063)

Würselen, 52146, Germany

Location

Pan and Aglaia Kyriakou Children s Hospital ( Site 0183)

Athens, 115 27, Greece

Location

University of Athens - Aghia Sophia Childrens Hospital ( Site 0185)

Athens, 115 27, Greece

Location

Attikon University General Hospital of Athens ( Site 0182)

Athens, 124 62, Greece

Location

University General Hospital of Larissa ( Site 0184)

Larissa, 411 10, Greece

Location

Hippokration General Hospital of Thessaloniki ( Site 0181)

Thessaloniki, 546 42, Greece

Location

Centrum Medyczne Pratia Bydgoszcz ( Site 0086)

Bydgoszcz, 85-796, Poland

Location

Prywatny Gabinet Lekarski Dr med Jerzy Brzostek ( Site 0084)

Dębica, 39-200, Poland

Location

Krakowski Szpital Specjalistyczny im. Jana Pawla II ( Site 0085)

Krakow, 31-202, Poland

Location

Gravita Diagnostyka i Leczenie Nieplodnosci ( Site 0092)

Lodz, 91-347, Poland

Location

SPZOZ Szpital Dzieciecy Poznan ( Site 0089)

Poznan, 61-709, Poland

Location

NZ Lecznictwa Ambulatoryjnego - Michalkowice - Jarosz i Partnerzy ( Site 0087)

Siemianowice Śląskie, 41-103, Poland

Location

Szpital im. sw. Jadwigi Slaskiej w Trzebnicy ( Site 0083)

Trzebnica, 55-100, Poland

Location

Uniwersytecki Szpital Kliniczny ( Site 0093)

Wroclaw, 50-368, Poland

Location

SPZOZ im. Dzieci Warszawy w Dziekanowie Lesnym ( Site 0091)

Łomianki, 05-092, Poland

Location

Central Clinical Hospital of Russian Academy Science ( Site 0052)

Moscow, 119333, Russia

Location

Children s City Polyclinic No. 45 of the Nevsky District ( Site 0048)

Saint Petersburg, 193312, Russia

Location

MAI Childrens City Clinical Hospital 11 ( Site 0047)

Yekaterinburg, 620034, Russia

Location

Hospital Universitari Germans Trias i Pujol ( Site 0102)

Badalona, Barcelona, 08916, Spain

Location

Hospital de Antequera ( Site 0111)

Antequera, Malaga, 29200, Spain

Location

Centro de Salud Paiporta ( Site 0117)

Paiporta, Valencia, 46200, Spain

Location

C.S. Quart de Poblet ( Site 0115)

Quart de Poblet, Valencia, 46930, Spain

Location

Hospital General Universitario 12 de Octubre ( Site 0106)

Madrid, 28041, Spain

Location

Hospital Universitario La Paz ( Site 0107)

Madrid, 28046, Spain

Location

Hospital Sanitas La Moraleja ( Site 0103)

Madrid, 28050, Spain

Location

Hospital Clinico Universitario de Santiago ( Site 0109)

Santiago de Compostela, 15706, Spain

Location

Unidad de Estudios e Investigacion IHP ( Site 0101)

Seville, 41014, Spain

Location

C.S. Serreria II ( Site 0116)

Valencia, 46022, Spain

Location

Centro de Salud Eliana ( Site 0114)

Valencia, 46183, Spain

Location

Related Publications (1)

• 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.

  PMID: 37105892 RESULT

MeSH Terms

Conditions

Pneumococcal Infections

Interventions

RIX4414 vaccine; 13-valent pneumococcal vaccine

Condition Hierarchy (Ancestors)

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

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: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2019
• First Posted: July 24, 2019
• Study Start: September 4, 2019
• Primary Completion: August 5, 2021
• Study Completion: August 5, 2021
• Last Updated: July 28, 2023
• Results First Posted: May 3, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will share

Locations

PL (9); AU (3); ES (11); GR (5); CZ (3); DE (14); BE (6); RU (3)