Safety, Tolerability, and Immunogenicity of a 3-dose Regimen of V114 in Healthy Infants (PNEU-PED-EU-2/V114-026)

Pneumococcal Infections Clinical Trial

— PNEU-PED-EU-2  

Official title:

A Phase 3, Multicenter, Randomized, Double-blind, Active-comparator-controlled Study to Evaluate the Safety, Tolerability, and Immunogenicity of a 3-dose Regimen of V114 in Healthy Infants (PNEU-PED-EU-2)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04016714
• Other study ID #: V114-026
• Secondary ID: V114-0262018-003
• Status: Completed
• Phase: Phase 3
• Start date: August 28, 2019
• Est. completion date: October 29, 2021

Study information

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

Clinical Trial Summary

The purpose of this clinical study is to evaluate the safety and immunogenicity of a 3-dose schedule (2-dose primary series followed by a toddler dose) of pneumococcal conjugate vaccine (PCV) as one of the currently recommended schedules by the World Health Organization (WHO) Strategic Advisory Group of Experts (SAGE) on Immunizations and practiced in many countries. The primary hypotheses are that V114 is non-inferior to Prevenar 13™ for the 13 shared serotypes based on response rates and on anti-pneumococcal polysaccharide (PnPs) serotype-specific Immunoglobulin G (IgG) geometric mean concentrations (GMCs) at 30 days following Dose 3; that V114 is superior to Prevenar 13™ for the 2 serotypes unique to V114 based on the response rates and on anti-PnPs serotype-specific IgG GMCs at 30 days following Dose 3; and that Vaxelis™ administered concomitantly with V114 is non-inferior to Vaxelis™ administered concomitantly with Prevenar 13™ at 30 days following Dose 3 for each antigen included in Vaxelis™.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1191
• Est. completion date: October 29, 2021
• Est. primary completion date: October 29, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 70 Days to 111 Days

Eligibility

Inclusion Criteria:

• Is male or female, approximately 3 months of age, from 70 days to 111 days inclusive, at the time of signing the informed consent.
• 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:

• Was born prior to 37 weeks of gestation.
• Has a history of invasive pneumococcal disease (IPD) or known history of other culture positive pneumococcal disease.
• Has a known hypersensitivity to any component of the pneumococcal conjugate vaccine (PCV), any component of the licensed pediatric vaccines to be administered concomitantly in the study, or any diphtheria toxoid containing vaccine.
• Has any contraindication to the concomitant study vaccines being administered in the study.
• 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 influenza type b conjugate vaccine, poliovirus 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.
• Has any other reason that, in the opinion of the investigator, may interfere with the evaluation required by the study. Reasons may include, but are not limited to, being unable to keep appointments or planning to relocate during the study.
• Is or has an immediate family member (e.g., 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:
• V114
15-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, 33F, serotype 6B and aluminum phosphate adjuvant in each 0.5 mL dose.
• Prevenar 13™
13-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F, serotype 6B in each 0.5. mL dose.
• Vaxelis™
Intramuscular 0.5 mL single dose
• M-M-R®II
Subcutaneous 0.5 mL single dose
• VARIVAX™
Subcutaneous 0.5 mL single dose

Locations

Country	Name	City	State
Denmark	Aalborg Universitetshospital ( Site 0005)	Aalborg	Nordjylland
Denmark	Aarhus Universitetshosp. Skejby ( Site 0002)	Aarhus	Midtjylland
Denmark	Regionshospitalet Herning Hospitalsenheden Vest ( Site 0006)	Herning	Midtjylland
Denmark	Sygehus Vendsyssel Hjoerring ( Site 0004)	Hjoerring	Nordjylland
Denmark	Hvidovre Hospital ( Site 0003)	Hvidovre	Hovedstaden
Denmark	Odense Universitetshospital ( Site 0001)	Odense C	Syddanmark
Finland	Tampereen yliopisto Espoon rokotetutkimusklinikka ( Site 0024)	Espoo	Uusimaa
Finland	Tampereen yliopisto Etela-Helsingin Rokotetutkimusklinikka ( Site 0022)	Helsinki	Uusimaa
Finland	Tampereen yliopisto Ita-Helsingin rokotetutkimusklinikka ( Site 0023)	Helsinki	Uusimaa
Finland	Jarvenpaan rokotetutkimuskeskus ( Site 0025)	Jarvenpaa	Uusimaa
Finland	Kokkolan rokotetutkimusklinikka ( Site 0029)	Kokkola	Mellersta Osterbotten
Finland	Tampereen yliopisto Oulun rokotetutkimusklinikka ( Site 0030)	Oulu	Pohjois-Pohjanmaa
Finland	Porin rokotetutkimusklinikka ( Site 0027)	Pori	Satakunta
Finland	Seinajoki Vaccine Research Center ( Site 0028)	Seinajoki	Sodra Osterbotten
Finland	Tampereen yliopisto - Tampereen rokotetutkimusklinikka ( Site 0021)	Tampere	Pirkanmaa
Finland	Turun rokotetutkimuskeskus ( Site 0026)	Turku	Varsinais-Suomi
Italy	A.O. Policlinico Consorziale di Bari ( Site 0044)	Bari
Italy	A.O.U. Riuniti Di Foggia - Igiene Universitaria ( Site 0046)	Foggia
Italy	IRCCS Ospedale Policlinico San Martino ( Site 0042)	Genova
Italy	Policlinico Universitario Agostino Gemelli ( Site 0048)	Rome	Roma
Norway	Oslo Universitetssykehus HF Ulleval Sykehus ( Site 0061)	Oslo
Norway	Stavanger universitetssykehus ( Site 0062)	Stavanger	Rogaland
Norway	Sykehuset i Vestfold ( Site 0063)	Toensberg	Vestfold
Sweden	Norrlands Universitetssjukhus ( Site 0100)	Umea	Vasterbottens Lan [se-24]

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

Denmark,  Finland,  Italy,  Norway,  Sweden, 

References & Publications (1)

Benfield T, Ramet M, Valentini P, Seppa I, Dagan R, Richmond P, Mercer S, Churchill C, Lupinacci R, McFetridge R, Park J, Wittke F, Banniettis N, Musey L, Bickham K, Kaminski J. Safety, tolerability, and immunogenicity of V114 pneumococcal vaccine compare — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With a Solicited Injection-site Adverse Event	An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Solicited injection-site AEs included injection-site erythema (redness), injection-site induration (hard lump), injection-site pain (tenderness), and injection-site swelling.	Day 1 to Day 14 after each vaccination
Primary	Percentage of Participants With a Solicited Systemic Adverse Event	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Solicited systemic AEs included decreased appetite, irritability, somnolence (drowsiness), and urticaria (hives or welts).	Day 1 to Day 14 after each vaccination
Primary	Percentage of Participants With a Vaccine-related Serious Adverse Event	A serious adverse event (SAE) is an AE that results in death, is life-threatening, requires or prolongs an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is another important medical event deemed such by medical or scientific judgment. SAEs that were reported by the investigator to be at least possibly related to the study vaccination were summarized.	Up to approximately 6 months after Dose 3 (up to approximately 16 months)
Primary	Percentage of Participants Meeting Serotype-specific Immunoglobulin G (IgG) Threshold Value of =0.35 µg/mL 30 Days After Dose 3	The geometric mean concentration (GMC) of IgG serotype-specific antibodies to the 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) included in V114 and Prevenar 13™ and 2 serotypes (22F and 33F) unique to V114 were quantitated from participants' sera by a multiplex electrochemiluminescence (ECL) assay. Immunoglobulin G for the 15 serotypes contained in V114 vaccine was determined using a pneumococcal electrochemiluminescence (PnECL) assay.	30 days after Dose 3
Primary	Geometric Mean Concentration (GMC) of Serotype-specific Immunoglobulin G (IgG) 30 Days After Dose 3	The GMC of IgG serotype-specific antibodies to the 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) included in V114 and Prevenar 13™ and 2 serotypes (22F and 33F) unique to V114 were quantitated from participants' sera by a multiplex electrochemiluminescence (ECL) assay.	30 days after Dose 3
Secondary	Percentage of Participants Meeting Specified Vaxelis™ Antigen Reponses 30 Days After Dose 3	Antigen-specific response rates in participants administered V114 concomitantly with Vaxelis™ were compared with response rates in participants administered Prevenar 13™ concomitantly with Vaxelis™, and the percentages of participants meeting specified Vaxelis™ antigen responses recorded. Antigens in Vaxelis™ include: diphtheria toxoid, tetanus toxoid, pertussis toxin (PT), pertussis filamentous hemagglutinin (FHA), pertussis fimbriae 2/3 (FIM 2/3), pertussis pertactin (PRN), Haemophilus influenzae type b polyribosylribitol phosphate (Hib-PRP), hepatitis B surface antigen (HBsAg), and poliovirus serotypes 1, 2, and 3.	30 days after Dose 3
Secondary	Percentage of Participants Meeting Serotype-specific IgG Threshold Value of =0.35 µg/mL 30 Days After Dose 2	The GMC of IgG serotype-specific antibodies to the 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) included in V114 and Prevenar 13™ and 2 serotypes (22F and 33F) unique to V114 were quantitated from participants' sera by a multiplex ECL assay. Immunoglobulin G for the 15 serotypes contained in V114 vaccine was determined using a PnECL assay.	30 days after Dose 2
Secondary	GMC of Serotype-specific IgG 30 Days After Dose 2	The GMC of IgG serotype-specific antibodies to the 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) included in V114 and Prevenar 13™ and 2 serotypes (22F and 33F) unique to V114 were quantitated from participants' sera by a multiplex ECL assay. Immunoglobulin G for the 15 serotypes contained in V114 vaccine was determined using a PnECL assay.	30 days after Dose 2
Secondary	Percentage of Participants Meeting Specified Opsonophagocytic Activity (OPA) Responses 30 Days After Dose 3	OPA for the 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) included in V114 and Prevenar 13™ and 2 serotypes unique to V114 (22F and 33F) was measured using a multiplex opsonophagocytic assay (MOPA).	30 days after Dose 3
Secondary	Geometric Mean Titers (GMTs) of Serotype-specific OPA 30 Days After Dose 3	Sera from participants was used to measure GMT of the 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) included in V114 and Prevenar 13™ and 2 serotypes unique to V114 (22F and 33F) was determined using a MOPA.	30 days after Dose 3