Safety, Tolerability, and Immunogenicity of V114 in Healthy Infants (V114-025) (PNEU-PED-EU-1)

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)

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.

Study Overview

• Status: Completed
• Conditions: Pneumococcal Infections
• Intervention / Treatment: Drug: Rotarix™; Drug: Infanrix™ hexa; Drug: V114; Drug: Prevenar 13™

• Study Type: Interventional
• Enrollment (Actual): 1184
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Nedlands, Australia, 6009
    • Telethon Kids Institute ( Site 0003)
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Queensland Children s Hospital ( Site 0004)
  • Victoria
    • Melbourne, Victoria, Australia, 3010
      • Vaccine and Immunisation Research Group - VIRGo ( Site 0002)
• Belgium
  • Aalst, Belgium, 9300
    • O.L.V. Ziekenhuis Aalst ( Site 0144)
  • Brugge, Belgium, 8000
    • AZ Sint Jan Brugge-Oostende ( Site 0147)
  • Gent, Belgium, 9000
    • AZ Maria Middelares Gent ( Site 0142)
  • Gent, Belgium, 9000
    • UZ Gent ( Site 0141)
  • Oostende, Belgium, 8400
    • AZ Henry Serruys ( Site 0148)
  • Roeselare, Belgium, 8800
    • AZ Delta ( Site 0143)
• Czechia
  • Jindrichuv Hradec, Czechia, 377 01
    • MUDr. Daniel Drazan - Prakticky lekar pro deti a dorost ( Site 0151)
  • Melnik, Czechia, 276 01
    • MU Dr. Jan Nemecek - Prakticky lekar pro deti a dorost ( Site 0152)
  • Tynec nad Sazavou, Czechia, 257 41
    • MUDr. Josef Zemanek ( Site 0153)
• Estonia
  • Tallinn, Estonia, 10617
    • Merekivi Perearstid ( Site 0165)
  • Tallinn, Estonia, 10617
    • Merelahe Perearstikeskus OU ( Site 0164)
  • Tallinn, Estonia, 11313
    • Sinu Arst Tervisekeskus ( Site 0167)
  • Tallinn, Estonia, 11315
    • Rosenthali Perearstikeskus OU ( Site 0166)
  • Tartu, Estonia, 50160
    • Kliiniliste Uuringute Keskus OU ( Site 0161)
  • Jarvamaa
    • Paide, Jarvamaa, Estonia, 72713
      • Vee Perearstikeskus ( Site 0163)
• Germany
  • Aschaffenburg, Germany, 63739
    • NETSTAP - Sandner ( Site 0072)
  • Bramsche, Germany, 49565
    • Kinderarztpraxis ( Site 0061)
  • Datteln, Germany, 45711
    • Praxis Dr. Schmute ( Site 0078)
  • Erfurt, Germany, 99086
    • Praxis fur Kinder und Jugendmedizin Eivy Franke Beckmann ( Site 0064)
  • Hamburg, Germany, 22415
    • Kinderarztpraxis Dr. Friedrich Kaiser & Dr. Marinesse ( Site 0065)
  • Herxheim, Germany, 76863
    • Kinderarztpraxis Dr. Juenger ( Site 0073)
  • Huerth, Germany, 50354
    • Kinderpraxis Dr. med. Andreas Petri ( Site 0066)
  • Moenchengladbach, Germany, 41236
    • Kinderarztpraxis ( Site 0068)
  • Oberhausen, Germany, 46145
    • Kinder- und Jugendaerztliche Gemeinschaftspraxis ( Site 0077)
  • Schoenau, Germany, 83471
    • Praxiszentrum Triftplatz ( Site 0075)
  • Schweigen, Germany, 76889
    • Praxis Dr. Siegfried Simmet ( Site 0069)
  • Tauberbischofsheim, Germany, 97941
    • Kinderarztpraxis Dr. Rolf Ebert & Dr. Matthias Huebener ( Site 0062)
  • Wolfsburg, Germany, 38448
    • Kinderaerztliche Gemeinschaftspraxis Drs. Westerholt/Matyas ( Site 0074)
  • Wuerselen, Germany, 52146
    • Kinderarztpraxis ( Site 0063)
• Greece
  • Athens, Greece, 115 27
    • Pan and Aglaia Kyriakou Children s Hospital ( Site 0183)
  • Athens, Greece, 115 27
    • University of Athens - Aghia Sophia Childrens Hospital ( Site 0185)
  • Athens, Greece, 124 62
    • Attikon University General Hospital of Athens ( Site 0182)
  • Larissa, Greece, 411 10
    • University General Hospital of Larissa ( Site 0184)
  • Thessaloniki, Greece, 546 42
    • Hippokration General Hospital of Thessaloniki ( Site 0181)
• Poland
  • Bydgoszcz, Poland, 85-796
    • Centrum Medyczne Pratia Bydgoszcz ( Site 0086)
  • Debica, Poland, 39-200
    • Prywatny Gabinet Lekarski Dr med Jerzy Brzostek ( Site 0084)
  • Krakow, Poland, 31-202
    • Krakowski Szpital Specjalistyczny im. Jana Pawla II ( Site 0085)
  • Lodz, Poland, 91-347
    • Gravita Diagnostyka i Leczenie Nieplodnosci ( Site 0092)
  • Lomianki, Poland, 05-092
    • SPZOZ im. Dzieci Warszawy w Dziekanowie Lesnym ( Site 0091)
  • Poznan, Poland, 61-709
    • SPZOZ Szpital Dzieciecy Poznan ( Site 0089)
  • Siemianowice Slaskie, Poland, 41-103
    • NZ Lecznictwa Ambulatoryjnego - Michalkowice - Jarosz i Partnerzy ( Site 0087)
  • Trzebnica, Poland, 55-100
    • Szpital im. sw. Jadwigi Slaskiej w Trzebnicy ( Site 0083)
  • Wroclaw, Poland, 50-368
    • Uniwersytecki Szpital Kliniczny ( Site 0093)
• Russian Federation
  • Ekaterinburg, Russian Federation, 620034
    • MAI Childrens City Clinical Hospital 11 ( Site 0047)
  • Moscow, Russian Federation, 119333
    • Central Clinical Hospital of Russian Academy Science ( Site 0052)
  • St.Petersburg, Russian Federation, 193312
    • Children s City Polyclinic No. 45 of the Nevsky District ( Site 0048)
• Spain
  • Madrid, Spain, 28041
    • Hospital General Universitario 12 de Octubre ( Site 0106)
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz ( Site 0107)
  • Madrid, Spain, 28050
    • Hospital Sanitas La Moraleja ( Site 0103)
  • Santiago de Compostela, Spain, 15706
    • Hospital Clinico Universitario de Santiago ( Site 0109)
  • Sevilla, Spain, 41014
    • Unidad de Estudios e Investigacion IHP ( Site 0101)
  • Valencia, Spain, 46022
    • C.S. Serreria II ( Site 0116)
  • Valencia, Spain, 46183
    • Centro de Salud Eliana ( Site 0114)
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Universitari Germans Trias i Pujol ( Site 0102)
  • Malaga
    • Antequera, Malaga, Spain, 29200
      • Hospital de Antequera ( Site 0111)
  • Valencia
    • Paiporta, Valencia, Spain, 46200
      • Centro de Salud Paiporta ( Site 0117)
    • Quart de Poblet, Valencia, Spain, 46930
      • C.S. Quart de Poblet ( Site 0115)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 2 months (Child)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: V114; 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™; Single 1.5 mL oral dose at 2 and 4 months of age (Study Day 1 and Month 2); Drug: Infanrix™ hexa; 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); Drug: V114; 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,; Other Names: VAXNEUVANCE™; Pneumococcal 15-Valent Conjugate Vaccine
Active Comparator: Prevenar 13™; 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™; Single 1.5 mL oral dose at 2 and 4 months of age (Study Day 1 and Month 2); Drug: Infanrix™ hexa; 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); Drug: Prevenar 13™; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Meet Antigen-Specific Threshold Value for Each Antigen in Infanrix™ Hexa at 30 Days PTD	Sera from participants was used to measure vaccine-induced responses to 10 pre-specified Infanrix™ hexa antigens with the following threshold (% ≥) values: Diphtheria toxoid-0.1 international unit (IU)/mL;Tetanus toxoid-0.1 IU/mL; Pertussis pertussis toxin (PT)-5 endotoxin unit (EU)/mL; Pertussis filamentous hemagglutinin (FHA)-5 EU/mL; Pertussis pertactin (PRN)-5 EU/mL; Haemophilus influenzae type b (Hib) polyribosylribitol phosphate (PRP)-0.15 μg/mL; hepatitis B surface antigen (HBsAg)-10 mIU/mL; Poliovirus 1,2 and 3-1:8 neutralizing antibodies (NAb) dilution.	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™	Sera from participants was used to measure vaccine-induced antibodies in response to vaccination with Rotarix™ by assessing the GMT for IgA. Per protocol, within-group CIs were not calculated.	30 days PPS (Up to approximately study month 3)
Anti-PnPs Serotype-specific IgG GMCs for Each Serotype at 30 Days PPS	Sera from participants was used to measure vaccine-induced anti-PnPs serotype-specific IgG for each serotype using PnECL. The 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 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	Sera from participants was used to measure vaccine-induced anti-PnPs serotype-specific IgG for the 15 serotypes using 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 PPS (Up to approximately study month 3)
Anti-PnPs Serotype-specific Opsonophagocytic Activity (OPA) GMTs for Each Serotype at 30 Days PTD	Sera from participants was used to measure vaccine-induced anti-PnPs serotype-specific OPA using the multiplexed opsonophagocytic assay (MOPA). The GMT 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. The within-group CIs were obtained by exponentiating the CIs of the mean of the natural log values based on the t-distribution.	30 days PTD (Up to approximately study month 14)
Percentage of Participants Who Meet Serotype-specific OPA Threshold Value for Each Serotype at 30 Days PTD	Sera from participants was used to measure vaccine-induced anti-PnPs serotype-specific OPA using the MOPA. The threshold dilution (% ≥) for each of the 13 serotypes shared by both V114 and Prevenar 13™ (Serotypes 1 to 23F) were as follows: 1:9, 1:19, 1:34, 1:27, 1:232, 1:40, 1:61, 1:151, 1:62, 1:115, 1:31, 1:113, 1:55. For Serotypes 22F and 33F the threshold dilution was 1:15 and 1:20 respectively. The within-group CIs were based on the exact binomial method of Clopper and Pearson.	30 days PTD (Up to approximately study month 14)
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	Sera from participants was used to measure vaccine-induced anti-PnPs serotype-specific IgG for the 15 serotypes using PnECL. As pre-specified in the protocol the percentage of participants from the two serotypes unique to V114 (Serotypes 22F and 33F) are presented, as well as the percentage of participants with the lowest response rate from any of the 13 shared serotypes randomized to Prevenar 13™ (Serotype 3).	30 days PTD (Up to approximately study month 14)

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 4, 2019
• Primary Completion (Actual): August 5, 2021
• Study Completion (Actual): August 5, 2021

Study Registration Dates

• First Submitted: July 22, 2019
• First Submitted That Met QC Criteria: July 22, 2019
• First Posted (Actual): July 24, 2019

Study Record Updates

• Last Update Posted (Actual): July 28, 2023
• Last Update Submitted That Met QC Criteria: July 20, 2023
• Last Verified: July 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; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: V114-025 (Other Identifier: Merck, Sharp & Dohme); 2018-003787-31 (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: No
• Studies a U.S. FDA-regulated device product: No