A Study to Evaluate the Safety and Tolerability of V114 and Prevnar 13™ in Healthy Infants (V114-031/PNEU-LINK)

A Phase 3, Multicenter, Randomized, Double-blind, Active Comparator-controlled Study to Evaluate the Safety and Tolerability of V114 in Healthy Infants (PNEU-LINK)

This study is designed to evaluate the safety and tolerability of V114 and Prevnar 13™ in healthy infants. This study will include both full-term infants (≥37 weeks gestational age) and premature infants (<37 weeks gestational age). Premature infants will be included in a Premature Infant Immunogenicity Substudy, which will assess immunogenicity and safety following administration of V114 or Prevnar 13™.

Study Overview

• Status: Completed
• Conditions: Pneumococcal Infections
• Intervention / Treatment: Biological: V114; Biological: Prevnar 13™

• Study Type: Interventional
• Enrollment (Actual): 2409
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Nedlands, Australia, 6009
    • Perth Children s Hospital ( Site 0092)
  • North Adelaide, Australia, 5087
    • Children, Youth and Woman's Health Service ( Site 0094)
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Children s Hospital ( Site 0093)
• Canada
  • Quebec, Canada, G1E 7G9
    • CHUQ - Unite de Recherche en Sante Publique ( Site 0042)
  • Alberta
    • Calgary, Alberta, Canada, T3B 6A8
      • Alberta Children s Hospital ( Site 0048)
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4H4
      • Vaccine Evaluation Center BC Children s Hospital Research Institute ( Site 0046)
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3K 6R8
      • IWK Health Centre [Halifax, Canada] ( Site 0043)
  • Ontario
    • Hamilton, Ontario, Canada, L8M 1K7
      • Hamilton Medical Research Group ( Site 0049)
    • Sudbury, Ontario, Canada, P3A 1Y8
      • Medicor Research Inc. ( Site 0041)
  • Quebec
    • Montreal, Quebec, Canada, H3T 1C5
      • CHU Sainte Justine ( Site 0047)
    • Pierrefonds, Quebec, Canada, H9H 4Y6
      • McGill University Health Centre - Vaccine Study Centre ( Site 0045)
• Finland
  • Espoo, Finland, 02230
    • Espoon rokotetutkimuskeskus ( Site 0066)
  • Helsinki, Finland, 00100
    • Tampereen yliopisto Etela-Helsingin Rokotetutkimusklinikka ( Site 0064)
  • Helsinki, Finland, 00930
    • Ita-Helsingin Rokotetutkimuskeskus ( Site 0065)
  • Jarvenpaa, Finland, 04400
    • Jarvenpaan rokotetutkimuskeskus ( Site 0067)
  • Kokkola, Finland, 67100
    • Kokkolan rokotetutkimusklinikka ( Site 0071)
  • Oulu, Finland, 90220
    • Tampereen yliopisto Oulun rokotetutkimusklinikka ( Site 0072)
  • Pori, Finland, 28100
    • Porin Rokotetutkimusklinikka ( Site 0069)
  • Seinajoki, Finland, 60100
    • Seinajoki Vaccine Research Center ( Site 0070)
  • Tampere, Finland, 33100
    • Tampereen yliopisto - Tampereen rokotetutkimusklinikka ( Site 0063)
  • Turku, Finland, 20520
    • Turun rokotetutkimuskeskus ( Site 0068)
• Germany
  • Aschaffenburg, Germany, 63739
    • Kinderarztpraxis ( Site 0124)
  • Bramsche, Germany, 49565
    • Kinderarztpraxis ( Site 0123)
  • Hamburg, Germany, 22415
    • Kinderarztpraxis Dr. Friedrich Kaiser & Dr. Marinesse ( Site 0085)
  • Huerth, Germany, 50354
    • Kinderarztpraxis ( Site 0081)
  • Lauffen, Germany, 74348
    • Kinderarztpraxis Dr. Muehlschlegel - Dr. Goetz ( Site 0122)
  • Moenchengladbach, Germany, 41236
    • Kinderarztpraxis ( Site 0080)
  • Munchengladbach, Germany, 41236
    • Kinderarztpraxis Matthias Donner Dr. M. Luechtrath ( Site 0091)
  • Schoenau, Germany, 83471
    • Kinderarztpraxis ( Site 0084)
  • Wolfsburg, Germany, 38448
    • Kinderaerztliche Gemeinschaftspraxis Drs. Westerholt/Matyas ( Site 0083)
• Israel
  • Beer Sheva, Israel, 8410101
    • Soroka University Medical Center ( Site 0077)
  • Beer-Sheva, Israel, 8471844
    • Soroka University Medical Center - Ramot Family health center ( Site 0078)
  • Haifa, Israel, 3109601
    • Rambam Medical Center ( Site 0076)
  • Haifa, Israel, 3515427
    • Rambam Medical Center- Keriat Eliezer Family Health Center ( Site 0138)
  • Haifa, Israel, 3542129
    • Rambam Medical Center- Neve David Family Health Center ( Site 0139)
  • Hura, Israel, 8573000
    • Soroka Medical Center_ Hura Family health center ( Site 0137)
  • Rahat, Israel, 8535700
    • Soroka University Medical Center - Rahat Family health center ( Site 0079)
• Malaysia
  • Kuala Lumpur, Malaysia, 59100
    • Universiti Malaya Medical Center-Clinical Investigation Center ( Site 0108)
  • Pelabuhan Klang, Malaysia, 42000
    • Klinik Kesihatan Pandamaran ( Site 0110)
  • Perak
    • Ipoh, Perak, Malaysia, 30450
      • Klinik Kesihatan Greentown ( Site 0132)
  • Sarawak
    • Kuching, Sarawak, Malaysia, 93586
      • Sarawak General Hospital ( Site 0107)
    • Sibu, Sarawak, Malaysia, 96000
      • Hospital Sibu ( Site 0111)
• Peru
  • Lima, Peru, 15001
    • Hospital Nacional Docente Madre - Nino San Bartolome ( Site 0057)
  • Lima, Peru, 15416
    • Instituto de Investigacion Nutricional ( Site 0058)
  • Trujillo, Peru, 13011
    • Clinica Peruano Americana S.A. ( Site 0061)
• Taiwan
  • Taichung, Taiwan, 407
    • Taichung Veterans General Hospital ( Site 0100)
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital ( Site 0097)
  • Taipei, Taiwan, 10491
    • Mackay Memorial Hospital ( Site 0099)
  • Taoyuan, Taiwan, 333
    • Chang Gung Medical Foundation. Linkou ( Site 0098)
• Thailand
  • Bangkok, Thailand, 10330
    • Chulalongkorn University ( Site 0102)
  • Bangkok, Thailand, 10700
    • Siriraj Hospital ( Site 0101)
  • Chiang Mai, Thailand, 50200
    • Maharaj Nakorn Chiang Mai Hospital ( Site 0103)
  • Hat Yai, Thailand, 90110
    • Prince of Songkla University, Faculty of Medicine ( Site 0105)
  • Khon Kaen, Thailand, 40002
    • Srinagarind Hospital. Khon Kaen University ( Site 0104)
• United States
  • California
    • Downey, California, United States, 90240
      • Premier Health Research Center, LLC ( Site 0005)
    • Huntington Beach, California, United States, 92647
      • Beach Pediatrics ( Site 0040)
    • San Diego, California, United States, 92102
      • Khruz Biotechnology Research Institute ( Site 0006)
    • San Jose, California, United States, 95119
      • Kaiser Permanente - San Jose ( Site 0036)
    • Santa Clara, California, United States, 95051
      • Kaiser Permanente - Santa Clara ( Site 0027)
  • Florida
    • Lake Mary, Florida, United States, 32746
      • Children's Research, LLC ( Site 0025)
    • Naples, Florida, United States, 34102
      • Advanced Research For Health Improvement LLC ( Site 0030)
  • Kansas
    • Overland Park, Kansas, United States, 66213
      • Pediatric Partners, P.A. ( Site 0010)
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Novak Center for Childrens Health ( Site 0033)
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Medpharmics, LLC ( Site 0037)
  • New York
    • East Syracuse, New York, United States, 13057
      • Child Health Care Associates ( Site 0024)
  • Ohio
    • Dayton, Ohio, United States, 45419
      • Primedical Clinical Research ( Site 0035)
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16506
      • Allegheny Health & Wellness Pavilion West ( Site 0034)
    • Hermitage, Pennsylvania, United States, 16148
      • CCP- Kid's Way ( Site 0008)
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University ( Site 0029)
  • South Carolina
    • Charleston, South Carolina, United States, 29407
      • Medical Research South, LLC ( Site 0013)
  • Texas
    • Houston, Texas, United States, 77087
      • Pediatric Associates [Houston, TX] ( Site 0039)
    • League City, Texas, United States, 77573
      • University of Texas Medical Branch ( Site 0018)
  • Utah
    • Layton, Utah, United States, 84041
      • Tanner Clinic ( Site 0009)
    • Layton, Utah, United States, 84041
      • Wee Care Pediatrics ( Site 0031)
    • Roy, Utah, United States, 84067
      • Wee Care Pediatrics ( Site 0020)
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin American Family Children's Hospital ( Site 0023)

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Healthy (based on a review of medical history and physical examination) based on the clinical judgment of the investigator
• Male or female approximately 2 months of age, from 42 days to 90 days inclusive, at the time of obtaining the informed consent
• Have 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
• Known hypersensitivity to any component of the pneumococcal conjugate vaccine (PCV) or any diphtheria toxoid containing vaccine
• Known or suspected impairment of immunological function
• History of congenital or acquired immunodeficiency
• Has or his/her mother has a documented human immunodeficiency virus (HIV) infection
• Known or history of functional or anatomic asplenia
• Failure to thrive based on the clinical judgment of the investigator
• Known coagulation disorder contraindicating intramuscular vaccination
• 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)
• Known neurologic or cognitive behavioral disorder, including encephalitis/myelitis, acute disseminating encephalomyelitis, pervasive development disorder, and related disorders
• Received a dose of any pneumococcal vaccine prior to study entry
• Received a blood transfusion or blood products, including immunoglobulins, before receipt of first dose of study vaccine
• 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.
• Has any other reason that, in the opinion of the investigator, may interfere with the evaluation required by the study
• Has an immediate family member 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; Participants will receive a single 0.5 mL intramuscular (IM) injection of V114 at approximately 2 months of age (Vaccination 1); approximately 4 months of age (Vaccination 2); approximately 6 months of age (Vaccination 3); and approximately 12-15 months of age (Vaccination 4).	Biological: V114; V114 pneumococcal capsular polysaccharide serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, 33F (2 mcg each), and serotype 6B (4 mcg) in each 0.5 mL dose; Other Names: VAXNEUVANCE™; Pneumococcal 15-Valent Conjugate Vaccine
Active Comparator: Prevnar 13™; Participants will receive a single 0.5 mL IM injection of Prevnar 13™ at approximately 2 months of age (Vaccination 1); approximately 4 months of age (Vaccination 2); approximately 6 months of age (Vaccination 3); and approximately 12-15 months of age (Vaccination 4).	Biological: Prevnar 13™; Prevnar 13™ pneumococcal capsular polysaccharide serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F (2.2 mcg each) and 6B (4.4 mcg) in each 0.5 ml dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to Day 14 after each study vaccination
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).	Up to Day 14 after each study vaccination
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 6 months after Vaccination 4 (up to 19 months after Vaccination 1)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Concentration (GMC) of Serotype-specific Immunoglobulin G (IgG) at 30 Days After Vaccination 3 (Premature Infants Only)	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 Prevnar 13™ and 2 serotypes (22F and 33F) unique to V114 were quantitated from participants' sera by a multiplex electrochemiluminescence (ECL) assay. This endpoint was part of a Premature Infant Immunogenicity Substudy.	30 days after Vaccination 3 (approximately 5 months after Vaccination 1)
GMC of Serotype-specific IgG Before Vaccination 4 (Premature Infants Only)	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 Prevnar 13™ and 2 serotypes (22F and 33F) unique to V114 were quantitated from participants' sera by a multiplex electrochemiluminescence (ECL) assay. This endpoint was part of a Premature Infant Immunogenicity Substudy.	Before Vaccination 4 (10-13 months after Vaccination 1)
GMC of Serotype-specific IgG at 30 Days After Vaccination 4 (Premature Infants Only)	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 Prevnar 13™ and 2 serotypes (22F and 33F) unique to V114 were quantitated from participants' sera by a multiplex electrochemiluminescence (ECL) assay. This endpoint was part of a Premature Infant Immunogenicity Substudy.	30 days after Vaccination 4 (11-14 months after Vaccination 1)
Percentage of Participants Meeting Serotype-specific IgG Threshold of ≥0.35 μg/mL 30 Days After Vaccination 3 (Premature Infants Only)	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 Prevnar 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. This endpoint was part of a Premature Infant Immunogenicity Substudy.	30 days after Vaccination 3 (approximately 5 months after Vaccination 1)

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Banniettis N, Horn M, Sadarangani M, Patel SM, Greenberg D, Oberdorfer P, Klein NP, Rupp R, Dagan R, Richmond P, Lumley J, Zhou W, Shi Y, Tamms G, Feemster K, Lupinacci R, Musey L, Bickham K; V114-031 (PNEU-LINK) study group. Safety and Tolerability of V114 Pneumococcal Vaccine in Infants: A Phase 3 Study. Pediatrics. 2023 Jul 1;152(1):e2022060428. doi: 10.1542/peds.2022-060428.

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2018
• Primary Completion (Actual): March 26, 2021
• Study Completion (Actual): March 26, 2021

Study Registration Dates

• First Submitted: September 28, 2018
• First Submitted That Met QC Criteria: September 28, 2018
• First Posted (Actual): October 2, 2018

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: V114-031 (Other Identifier: Merck); 2018-003308-38 (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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No