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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04031846




Registration number
NCT04031846
Ethics application status
Date submitted
22/07/2019
Date registered
24/07/2019
Date last updated
28/07/2023

Titles & IDs
Public title
Safety, Tolerability, and Immunogenicity of V114 in Healthy Infants (V114-025)
Scientific 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)
Secondary ID [1] 0 0
V114-025
Secondary ID [2] 0 0
V114-025
Universal Trial Number (UTN)
Trial acronym
PNEU-PED-EU-1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pneumococcal Infections 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Rotarix™
Treatment: Drugs - Infanrix™ hexa
Treatment: Drugs - V114
Treatment: Drugs - Prevenar 13™

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.

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.


Treatment: Drugs: Rotarix™
Single 1.5 mL oral dose at 2 and 4 months of age (Study Day 1 and Month 2)

Treatment: Drugs: 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)

Treatment: Drugs: 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,

Treatment: Drugs: 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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants That Report at Least 1 Solicited Injection-site Adverse Event (AE)
Timepoint [1] 0 0
Up to 14 days post any vaccination (up to approximately study month 13)
Primary outcome [2] 0 0
Percentage of Participants That Report at Least 1 Solicited Systemic AE
Timepoint [2] 0 0
Up to 14 days post any vaccination (up to approximately study month 13)
Primary outcome [3] 0 0
Percentage of Participants That Report at Least 1 Vaccine-related Serious Adverse Event (SAE)
Timepoint [3] 0 0
Up to 6 months post last vaccination (up to approximately study month 20)
Primary outcome [4] 0 0
Anti-pneumococcal Polysaccharide (PnPs) Serotype-specific Immunoglobin G (IgG) Geometric Mean Concentrations (GMC) for Each Serotype at 30 Days Post Toddler Dose (PTD)
Timepoint [4] 0 0
30 days PTD (Up to approximately study month 14)
Primary outcome [5] 0 0
Percentage of Participants Who Meet Serotype-specific IgG Threshold Value of =0.35 µg/mL for Each Serotype at 30 Days PTD
Timepoint [5] 0 0
30 days PTD (Up to approximately study month 14)
Secondary outcome [1] 0 0
Percentage of Participants Who Meet Antigen-Specific Threshold Value for Each Antigen in Infanrix™ Hexa at 30 Days PTD
Timepoint [1] 0 0
30 days PTD (Up to approximately study month 14)
Secondary outcome [2] 0 0
Anti-rotavirus Immunoglobulin A (IgA) Geometric Mean Titers (GMTs) at 30 Days Post Primary Series (PPS) of Rotarix™
Timepoint [2] 0 0
30 days PPS (Up to approximately study month 3)
Secondary outcome [3] 0 0
Anti-PnPs Serotype-specific IgG GMCs for Each Serotype at 30 Days PPS
Timepoint [3] 0 0
30 days PPS (Up to approximately study month 3)
Secondary outcome [4] 0 0
Percentage of Participants Who Meet Serotype-specific IgG Threshold Value of =0.35 µg/mL for Each Serotype at 30 Days PPS
Timepoint [4] 0 0
30 days PPS (Up to approximately study month 3)
Secondary outcome [5] 0 0
Anti-PnPs Serotype-specific Opsonophagocytic Activity (OPA) GMTs for Each Serotype at 30 Days PTD
Timepoint [5] 0 0
30 days PTD (Up to approximately study month 14)
Secondary outcome [6] 0 0
Percentage of Participants Who Meet Serotype-specific OPA Threshold Value for Each Serotype at 30 Days PTD
Timepoint [6] 0 0
30 days PTD (Up to approximately study month 14)
Secondary outcome [7] 0 0
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
Timepoint [7] 0 0
30 days PTD (Up to approximately study month 14)

Eligibility
Key inclusion 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
Minimum age
42 Days
Maximum age
90 Days
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
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 design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
4/09/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
5/08/2021
Sample size
Target
Accrual to date
Final
1184
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
Queensland Children s Hospital ( Site 0004) - South Brisbane
Recruitment hospital [2] 0 0
Vaccine and Immunisation Research Group - VIRGo ( Site 0002) - Melbourne
Recruitment hospital [3] 0 0
Telethon Kids Institute ( Site 0003) - Nedlands
Recruitment postcode(s) [1] 0 0
4101 - South Brisbane
Recruitment postcode(s) [2] 0 0
3010 - Melbourne
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Aalst
Country [2] 0 0
Belgium
State/province [2] 0 0
Brugge
Country [3] 0 0
Belgium
State/province [3] 0 0
Gent
Country [4] 0 0
Belgium
State/province [4] 0 0
Oostende
Country [5] 0 0
Belgium
State/province [5] 0 0
Roeselare
Country [6] 0 0
Czechia
State/province [6] 0 0
Jindrichuv Hradec
Country [7] 0 0
Czechia
State/province [7] 0 0
Melnik
Country [8] 0 0
Czechia
State/province [8] 0 0
Tynec nad Sazavou
Country [9] 0 0
Estonia
State/province [9] 0 0
Jarvamaa
Country [10] 0 0
Estonia
State/province [10] 0 0
Tallinn
Country [11] 0 0
Estonia
State/province [11] 0 0
Tartu
Country [12] 0 0
Germany
State/province [12] 0 0
Aschaffenburg
Country [13] 0 0
Germany
State/province [13] 0 0
Bramsche
Country [14] 0 0
Germany
State/province [14] 0 0
Datteln
Country [15] 0 0
Germany
State/province [15] 0 0
Erfurt
Country [16] 0 0
Germany
State/province [16] 0 0
Hamburg
Country [17] 0 0
Germany
State/province [17] 0 0
Herxheim
Country [18] 0 0
Germany
State/province [18] 0 0
Huerth
Country [19] 0 0
Germany
State/province [19] 0 0
Moenchengladbach
Country [20] 0 0
Germany
State/province [20] 0 0
Oberhausen
Country [21] 0 0
Germany
State/province [21] 0 0
Schoenau
Country [22] 0 0
Germany
State/province [22] 0 0
Schweigen
Country [23] 0 0
Germany
State/province [23] 0 0
Tauberbischofsheim
Country [24] 0 0
Germany
State/province [24] 0 0
Wolfsburg
Country [25] 0 0
Germany
State/province [25] 0 0
Wuerselen
Country [26] 0 0
Greece
State/province [26] 0 0
Athens
Country [27] 0 0
Greece
State/province [27] 0 0
Larissa
Country [28] 0 0
Greece
State/province [28] 0 0
Thessaloniki
Country [29] 0 0
Poland
State/province [29] 0 0
Bydgoszcz
Country [30] 0 0
Poland
State/province [30] 0 0
Debica
Country [31] 0 0
Poland
State/province [31] 0 0
Krakow
Country [32] 0 0
Poland
State/province [32] 0 0
Lodz
Country [33] 0 0
Poland
State/province [33] 0 0
Lomianki
Country [34] 0 0
Poland
State/province [34] 0 0
Poznan
Country [35] 0 0
Poland
State/province [35] 0 0
Siemianowice Slaskie
Country [36] 0 0
Poland
State/province [36] 0 0
Trzebnica
Country [37] 0 0
Poland
State/province [37] 0 0
Wroclaw
Country [38] 0 0
Russian Federation
State/province [38] 0 0
Ekaterinburg
Country [39] 0 0
Russian Federation
State/province [39] 0 0
Moscow
Country [40] 0 0
Russian Federation
State/province [40] 0 0
St.Petersburg
Country [41] 0 0
Spain
State/province [41] 0 0
Barcelona
Country [42] 0 0
Spain
State/province [42] 0 0
Malaga
Country [43] 0 0
Spain
State/province [43] 0 0
Valencia
Country [44] 0 0
Spain
State/province [44] 0 0
Madrid
Country [45] 0 0
Spain
State/province [45] 0 0
Santiago de Compostela
Country [46] 0 0
Spain
State/province [46] 0 0
Sevilla

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT04031846
Trial related presentations / 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.
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04031846