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

Pneumococcal Infections Clinical Trial

— PNEU-PED-EU-1  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04031846
• Other study ID #: V114-025
• Secondary ID: V114-0252018-003
• Status: Completed
• Phase: Phase 3
• Start date: September 4, 2019
• Est. completion date: August 5, 2021

Study information

• Verified date: July 2023
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1184
• Est. completion date: August 5, 2021
• Est. primary completion date: August 5, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 42 Days to 90 Days

Eligibility

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

Related Conditions & MeSH terms

• Pneumococcal Infections

Intervention

Drug:
• Rotarix™
Single 1.5 mL oral dose at 2 and 4 months of age (Study Day 1 and Month 2)
• 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)
• 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,
• 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.

Locations

Country	Name	City	State
Australia	Vaccine and Immunisation Research Group - VIRGo ( Site 0002)	Melbourne	Victoria
Australia	Telethon Kids Institute ( Site 0003)	Nedlands
Australia	Queensland Children s Hospital ( Site 0004)	South Brisbane	Queensland
Belgium	O.L.V. Ziekenhuis Aalst ( Site 0144)	Aalst
Belgium	AZ Sint Jan Brugge-Oostende ( Site 0147)	Brugge
Belgium	AZ Maria Middelares Gent ( Site 0142)	Gent
Belgium	UZ Gent ( Site 0141)	Gent
Belgium	AZ Henry Serruys ( Site 0148)	Oostende
Belgium	AZ Delta ( Site 0143)	Roeselare
Czechia	MUDr. Daniel Drazan - Prakticky lekar pro deti a dorost ( Site 0151)	Jindrichuv Hradec
Czechia	MU Dr. Jan Nemecek - Prakticky lekar pro deti a dorost ( Site 0152)	Melnik
Czechia	MUDr. Josef Zemanek ( Site 0153)	Tynec nad Sazavou
Estonia	Vee Perearstikeskus ( Site 0163)	Paide	Jarvamaa
Estonia	Merekivi Perearstid ( Site 0165)	Tallinn
Estonia	Merelahe Perearstikeskus OU ( Site 0164)	Tallinn
Estonia	Rosenthali Perearstikeskus OU ( Site 0166)	Tallinn
Estonia	Sinu Arst Tervisekeskus ( Site 0167)	Tallinn
Estonia	Kliiniliste Uuringute Keskus OU ( Site 0161)	Tartu
Germany	NETSTAP - Sandner ( Site 0072)	Aschaffenburg
Germany	Kinderarztpraxis ( Site 0061)	Bramsche
Germany	Praxis Dr. Schmute ( Site 0078)	Datteln
Germany	Praxis fur Kinder und Jugendmedizin Eivy Franke Beckmann ( Site 0064)	Erfurt
Germany	Kinderarztpraxis Dr. Friedrich Kaiser & Dr. Marinesse ( Site 0065)	Hamburg
Germany	Kinderarztpraxis Dr. Juenger ( Site 0073)	Herxheim
Germany	Kinderpraxis Dr. med. Andreas Petri ( Site 0066)	Huerth
Germany	Kinderarztpraxis ( Site 0068)	Moenchengladbach
Germany	Kinder- und Jugendaerztliche Gemeinschaftspraxis ( Site 0077)	Oberhausen
Germany	Praxiszentrum Triftplatz ( Site 0075)	Schoenau
Germany	Praxis Dr. Siegfried Simmet ( Site 0069)	Schweigen
Germany	Kinderarztpraxis Dr. Rolf Ebert & Dr. Matthias Huebener ( Site 0062)	Tauberbischofsheim
Germany	Kinderaerztliche Gemeinschaftspraxis Drs. Westerholt/Matyas ( Site 0074)	Wolfsburg
Germany	Kinderarztpraxis ( Site 0063)	Wuerselen
Greece	Attikon University General Hospital of Athens ( Site 0182)	Athens
Greece	Pan and Aglaia Kyriakou Children s Hospital ( Site 0183)	Athens
Greece	University of Athens - Aghia Sophia Childrens Hospital ( Site 0185)	Athens
Greece	University General Hospital of Larissa ( Site 0184)	Larissa
Greece	Hippokration General Hospital of Thessaloniki ( Site 0181)	Thessaloniki
Poland	Centrum Medyczne Pratia Bydgoszcz ( Site 0086)	Bydgoszcz
Poland	Prywatny Gabinet Lekarski Dr med Jerzy Brzostek ( Site 0084)	Debica
Poland	Krakowski Szpital Specjalistyczny im. Jana Pawla II ( Site 0085)	Krakow
Poland	Gravita Diagnostyka i Leczenie Nieplodnosci ( Site 0092)	Lodz
Poland	SPZOZ im. Dzieci Warszawy w Dziekanowie Lesnym ( Site 0091)	Lomianki
Poland	SPZOZ Szpital Dzieciecy Poznan ( Site 0089)	Poznan
Poland	NZ Lecznictwa Ambulatoryjnego - Michalkowice - Jarosz i Partnerzy ( Site 0087)	Siemianowice Slaskie
Poland	Szpital im. sw. Jadwigi Slaskiej w Trzebnicy ( Site 0083)	Trzebnica
Poland	Uniwersytecki Szpital Kliniczny ( Site 0093)	Wroclaw
Russian Federation	MAI Childrens City Clinical Hospital 11 ( Site 0047)	Ekaterinburg
Russian Federation	Central Clinical Hospital of Russian Academy Science ( Site 0052)	Moscow
Russian Federation	Children s City Polyclinic No. 45 of the Nevsky District ( Site 0048)	St.Petersburg
Spain	Hospital de Antequera ( Site 0111)	Antequera	Malaga
Spain	Hospital Universitari Germans Trias i Pujol ( Site 0102)	Badalona	Barcelona
Spain	Hospital General Universitario 12 de Octubre ( Site 0106)	Madrid
Spain	Hospital Sanitas La Moraleja ( Site 0103)	Madrid
Spain	Hospital Universitario La Paz ( Site 0107)	Madrid
Spain	Centro de Salud Paiporta ( Site 0117)	Paiporta	Valencia
Spain	C.S. Quart de Poblet ( Site 0115)	Quart de Poblet	Valencia
Spain	Hospital Clinico Universitario de Santiago ( Site 0109)	Santiago de Compostela
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

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

Australia,  Belgium,  Czechia,  Estonia,  Germany,  Greece,  Poland,  Russian Federation,  Spain, 

References & 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 stu — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)