Safety, Tolerability, and Immunogenicity of V114 in Healthy Infants (V114-025)
- Conditions
- Pneumococcal Infections
- Interventions
- Registration Number
- NCT04031846
- Lead Sponsor
- Merck Sharp & Dohme LLC
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1184
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Prevenar 13™ Rotarix™ 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. Prevenar 13™ Infanrix™ hexa 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. Prevenar 13™ 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. V114 Rotarix™ 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. V114 Infanrix™ hexa 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. V114 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.
- Primary Outcome Measures
Name Time Method Anti-pneumococcal Polysaccharide (PnPs) Serotype-specific Immunoglobin G (IgG) Geometric Mean Concentrations (GMC) for Each Serotype at 30 Days Post Toddler Dose (PTD) 30 days PTD (Up to approximately study month 14) 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.
Percentage of Participants That Report at Least 1 Solicited Injection-site Adverse Event (AE) Up to 14 days post any vaccination (up to approximately study month 13) 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.
Percentage of Participants That Report at Least 1 Solicited Systemic AE Up to 14 days post any vaccination (up to approximately study month 13) 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).
Percentage of Participants That Report at Least 1 Vaccine-related Serious Adverse Event (SAE) Up to 6 months post last vaccination (up to approximately study month 20) 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.
Percentage of Participants Who Meet Serotype-specific IgG Threshold Value of ≥0.35 μg/mL for Each Serotype at 30 Days PTD 30 days PTD (Up to approximately study month 14) 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.
- Secondary Outcome Measures
Name Time Method 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) 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.
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) 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.
Anti-PnPs Serotype-specific IgG GMCs for Each Serotype at 30 Days PPS 30 days PPS (Up to approximately study month 3) 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.
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) 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.
Anti-PnPs Serotype-specific Opsonophagocytic Activity (OPA) GMTs for Each Serotype at 30 Days PTD 30 days PTD (Up to approximately study month 14) 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.
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 30 days PTD (Up to approximately study month 14) 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).
Percentage of Participants Who Meet Serotype-specific OPA Threshold Value for Each Serotype at 30 Days PTD 30 days PTD (Up to approximately study month 14) 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.
Trial Locations
- Locations (60)
O.L.V. Ziekenhuis Aalst ( Site 0144)
🇧🇪Aalst, Belgium
AZ Sint Jan Brugge-Oostende ( Site 0147)
🇧🇪Brugge, Belgium
Centro de Salud Paiporta ( Site 0117)
🇪🇸Paiporta, Valencia, Spain
C.S. Quart de Poblet ( Site 0115)
🇪🇸Quart de Poblet, Valencia, Spain
Queensland Children s Hospital ( Site 0004)
🇦🇺South Brisbane, Queensland, Australia
Telethon Kids Institute ( Site 0003)
🇦🇺Nedlands, Australia
AZ Maria Middelares Gent ( Site 0142)
🇧🇪Gent, Belgium
UZ Gent ( Site 0141)
🇧🇪Gent, Belgium
AZ Delta ( Site 0143)
🇧🇪Roeselare, Belgium
MUDr. Daniel Drazan - Prakticky lekar pro deti a dorost ( Site 0151)
🇨🇿Jindrichuv Hradec, Czechia
Kinderarztpraxis ( Site 0061)
🇩🇪Bramsche, Germany
Merekivi Perearstid ( Site 0165)
🇪🇪Tallinn, Estonia
Merelahe Perearstikeskus OU ( Site 0164)
🇪🇪Tallinn, Estonia
Praxis Dr. Schmute ( Site 0078)
🇩🇪Datteln, Germany
MUDr. Josef Zemanek ( Site 0153)
🇨🇿Tynec nad Sazavou, Czechia
Vee Perearstikeskus ( Site 0163)
🇪🇪Paide, Jarvamaa, Estonia
Rosenthali Perearstikeskus OU ( Site 0166)
🇪🇪Tallinn, Estonia
Kliiniliste Uuringute Keskus OU ( Site 0161)
🇪🇪Tartu, Estonia
NETSTAP - Sandner ( Site 0072)
🇩🇪Aschaffenburg, Germany
Kinderarztpraxis Dr. Friedrich Kaiser & Dr. Marinesse ( Site 0065)
🇩🇪Hamburg, Germany
Kinderpraxis Dr. med. Andreas Petri ( Site 0066)
🇩🇪Huerth, Germany
Praxiszentrum Triftplatz ( Site 0075)
🇩🇪Schoenau, Germany
Kinderaerztliche Gemeinschaftspraxis Drs. Westerholt/Matyas ( Site 0074)
🇩🇪Wolfsburg, Germany
Hippokration General Hospital of Thessaloniki ( Site 0181)
🇬🇷Thessaloniki, Greece
Centrum Medyczne Pratia Bydgoszcz ( Site 0086)
🇵🇱Bydgoszcz, Poland
Krakowski Szpital Specjalistyczny im. Jana Pawla II ( Site 0085)
🇵🇱Krakow, Poland
Kinderarztpraxis ( Site 0063)
🇩🇪Wuerselen, Germany
University General Hospital of Larissa ( Site 0184)
🇬🇷Larissa, Greece
Szpital im. sw. Jadwigi Slaskiej w Trzebnicy ( Site 0083)
🇵🇱Trzebnica, Poland
Hospital de Antequera ( Site 0111)
🇪🇸Antequera, Malaga, Spain
Hospital General Universitario 12 de Octubre ( Site 0106)
🇪🇸Madrid, Spain
Hospital Clinico Universitario de Santiago ( Site 0109)
🇪🇸Santiago de Compostela, Spain
Hospital Sanitas La Moraleja ( Site 0103)
🇪🇸Madrid, Spain
Kinderarztpraxis Dr. Juenger ( Site 0073)
🇩🇪Herxheim, Germany
Kinderarztpraxis ( Site 0068)
🇩🇪Moenchengladbach, Germany
Kinder- und Jugendaerztliche Gemeinschaftspraxis ( Site 0077)
🇩🇪Oberhausen, Germany
Hospital Universitario La Paz ( Site 0107)
🇪🇸Madrid, Spain
Sinu Arst Tervisekeskus ( Site 0167)
🇪🇪Tallinn, Estonia
MU Dr. Jan Nemecek - Prakticky lekar pro deti a dorost ( Site 0152)
🇨🇿Melnik, Czechia
Praxis fur Kinder und Jugendmedizin Eivy Franke Beckmann ( Site 0064)
🇩🇪Erfurt, Germany
Praxis Dr. Siegfried Simmet ( Site 0069)
🇩🇪Schweigen, Germany
Kinderarztpraxis Dr. Rolf Ebert & Dr. Matthias Huebener ( Site 0062)
🇩🇪Tauberbischofsheim, Germany
Pan and Aglaia Kyriakou Children s Hospital ( Site 0183)
🇬🇷Athens, Greece
University of Athens - Aghia Sophia Childrens Hospital ( Site 0185)
🇬🇷Athens, Greece
Attikon University General Hospital of Athens ( Site 0182)
🇬🇷Athens, Greece
SPZOZ im. Dzieci Warszawy w Dziekanowie Lesnym ( Site 0091)
🇵🇱Lomianki, Poland
MAI Childrens City Clinical Hospital 11 ( Site 0047)
🇷🇺Ekaterinburg, Russian Federation
Children s City Polyclinic No. 45 of the Nevsky District ( Site 0048)
🇷🇺St.Petersburg, Russian Federation
Central Clinical Hospital of Russian Academy Science ( Site 0052)
🇷🇺Moscow, Russian Federation
Hospital Universitari Germans Trias i Pujol ( Site 0102)
🇪🇸Badalona, Barcelona, Spain
Unidad de Estudios e Investigacion IHP ( Site 0101)
🇪🇸Sevilla, Spain
C.S. Serreria II ( Site 0116)
🇪🇸Valencia, Spain
Centro de Salud Eliana ( Site 0114)
🇪🇸Valencia, Spain
AZ Henry Serruys ( Site 0148)
🇧🇪Oostende, Belgium
Prywatny Gabinet Lekarski Dr med Jerzy Brzostek ( Site 0084)
🇵🇱Debica, Poland
SPZOZ Szpital Dzieciecy Poznan ( Site 0089)
🇵🇱Poznan, Poland
NZ Lecznictwa Ambulatoryjnego - Michalkowice - Jarosz i Partnerzy ( Site 0087)
🇵🇱Siemianowice Slaskie, Poland
Gravita Diagnostyka i Leczenie Nieplodnosci ( Site 0092)
🇵🇱Lodz, Poland
Uniwersytecki Szpital Kliniczny ( Site 0093)
🇵🇱Wroclaw, Poland
Vaccine and Immunisation Research Group - VIRGo ( Site 0002)
🇦🇺Melbourne, Victoria, Australia