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

Pneumococcal Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03692871
• Other study ID #: V114-031
• Secondary ID: V114-0312018-003
• Status: Completed
• Phase: Phase 3
• Start date: December 14, 2018
• Est. completion date: March 26, 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 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™.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2409
• Est. completion date: March 26, 2021
• Est. primary completion date: March 26, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 42 Days to 90 Days

Eligibility

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.

Related Conditions & MeSH terms

• Pneumococcal Infections

Intervention

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
• 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

Locations

Country	Name	City	State
Australia	Monash Children s Hospital ( Site 0093)	Clayton	Victoria
Australia	Perth Children s Hospital ( Site 0092)	Nedlands
Australia	Children, Youth and Woman's Health Service ( Site 0094)	North Adelaide
Canada	Alberta Children s Hospital ( Site 0048)	Calgary	Alberta
Canada	IWK Health Centre [Halifax, Canada] ( Site 0043)	Halifax	Nova Scotia
Canada	Hamilton Medical Research Group ( Site 0049)	Hamilton	Ontario
Canada	CHU Sainte Justine ( Site 0047)	Montreal	Quebec
Canada	McGill University Health Centre - Vaccine Study Centre ( Site 0045)	Pierrefonds	Quebec
Canada	CHUQ - Unite de Recherche en Sante Publique ( Site 0042)	Quebec
Canada	Medicor Research Inc. ( Site 0041)	Sudbury	Ontario
Canada	Vaccine Evaluation Center BC Children s Hospital Research Institute ( Site 0046)	Vancouver	British Columbia
Finland	Espoon rokotetutkimuskeskus ( Site 0066)	Espoo
Finland	Ita-Helsingin Rokotetutkimuskeskus ( Site 0065)	Helsinki
Finland	Tampereen yliopisto Etela-Helsingin Rokotetutkimusklinikka ( Site 0064)	Helsinki
Finland	Jarvenpaan rokotetutkimuskeskus ( Site 0067)	Jarvenpaa
Finland	Kokkolan rokotetutkimusklinikka ( Site 0071)	Kokkola
Finland	Tampereen yliopisto Oulun rokotetutkimusklinikka ( Site 0072)	Oulu
Finland	Porin Rokotetutkimusklinikka ( Site 0069)	Pori
Finland	Seinajoki Vaccine Research Center ( Site 0070)	Seinajoki
Finland	Tampereen yliopisto - Tampereen rokotetutkimusklinikka ( Site 0063)	Tampere
Finland	Turun rokotetutkimuskeskus ( Site 0068)	Turku
Germany	Kinderarztpraxis ( Site 0124)	Aschaffenburg
Germany	Kinderarztpraxis ( Site 0123)	Bramsche
Germany	Kinderarztpraxis Dr. Friedrich Kaiser & Dr. Marinesse ( Site 0085)	Hamburg
Germany	Kinderarztpraxis ( Site 0081)	Huerth
Germany	Kinderarztpraxis Dr. Muehlschlegel - Dr. Goetz ( Site 0122)	Lauffen
Germany	Kinderarztpraxis ( Site 0080)	Moenchengladbach
Germany	Kinderarztpraxis Matthias Donner Dr. M. Luechtrath ( Site 0091)	Munchengladbach
Germany	Kinderarztpraxis ( Site 0084)	Schoenau
Germany	Kinderaerztliche Gemeinschaftspraxis Drs. Westerholt/Matyas ( Site 0083)	Wolfsburg
Israel	Soroka University Medical Center ( Site 0077)	Beer Sheva
Israel	Soroka University Medical Center - Ramot Family health center ( Site 0078)	Beer-Sheva
Israel	Rambam Medical Center ( Site 0076)	Haifa
Israel	Rambam Medical Center- Keriat Eliezer Family Health Center ( Site 0138)	Haifa
Israel	Rambam Medical Center- Neve David Family Health Center ( Site 0139)	Haifa
Israel	Soroka Medical Center_ Hura Family health center ( Site 0137)	Hura
Israel	Soroka University Medical Center - Rahat Family health center ( Site 0079)	Rahat
Malaysia	Klinik Kesihatan Greentown ( Site 0132)	Ipoh	Perak
Malaysia	Universiti Malaya Medical Center-Clinical Investigation Center ( Site 0108)	Kuala Lumpur
Malaysia	Sarawak General Hospital ( Site 0107)	Kuching	Sarawak
Malaysia	Klinik Kesihatan Pandamaran ( Site 0110)	Pelabuhan Klang
Malaysia	Hospital Sibu ( Site 0111)	Sibu	Sarawak
Peru	Hospital Nacional Docente Madre - Nino San Bartolome ( Site 0057)	Lima
Peru	Instituto de Investigacion Nutricional ( Site 0058)	Lima
Peru	Clinica Peruano Americana S.A. ( Site 0061)	Trujillo
Taiwan	Taichung Veterans General Hospital ( Site 0100)	Taichung
Taiwan	Mackay Memorial Hospital ( Site 0099)	Taipei
Taiwan	National Taiwan University Hospital ( Site 0097)	Taipei
Taiwan	Chang Gung Medical Foundation. Linkou ( Site 0098)	Taoyuan
Thailand	Chulalongkorn University ( Site 0102)	Bangkok
Thailand	Siriraj Hospital ( Site 0101)	Bangkok
Thailand	Maharaj Nakorn Chiang Mai Hospital ( Site 0103)	Chiang Mai
Thailand	Prince of Songkla University, Faculty of Medicine ( Site 0105)	Hat Yai
Thailand	Srinagarind Hospital. Khon Kaen University ( Site 0104)	Khon Kaen
United States	Medical Research South, LLC ( Site 0013)	Charleston	South Carolina
United States	Primedical Clinical Research ( Site 0035)	Dayton	Ohio
United States	Premier Health Research Center, LLC ( Site 0005)	Downey	California
United States	Child Health Care Associates ( Site 0024)	East Syracuse	New York
United States	Allegheny Health & Wellness Pavilion West ( Site 0034)	Erie	Pennsylvania
United States	CCP- Kid's Way ( Site 0008)	Hermitage	Pennsylvania
United States	Pediatric Associates [Houston, TX] ( Site 0039)	Houston	Texas
United States	Beach Pediatrics ( Site 0040)	Huntington Beach	California
United States	Children's Research, LLC ( Site 0025)	Lake Mary	Florida
United States	Tanner Clinic ( Site 0009)	Layton	Utah
United States	Wee Care Pediatrics ( Site 0031)	Layton	Utah
United States	University of Texas Medical Branch ( Site 0018)	League City	Texas
United States	Novak Center for Childrens Health ( Site 0033)	Louisville	Kentucky
United States	University of Wisconsin American Family Children's Hospital ( Site 0023)	Madison	Wisconsin
United States	Medpharmics, LLC ( Site 0037)	Metairie	Louisiana
United States	Advanced Research For Health Improvement LLC ( Site 0030)	Naples	Florida
United States	Pediatric Partners, P.A. ( Site 0010)	Overland Park	Kansas
United States	Thomas Jefferson University ( Site 0029)	Philadelphia	Pennsylvania
United States	Wee Care Pediatrics ( Site 0020)	Roy	Utah
United States	Khruz Biotechnology Research Institute ( Site 0006)	San Diego	California
United States	Kaiser Permanente - San Jose ( Site 0036)	San Jose	California
United States	Kaiser Permanente - Santa Clara ( Site 0027)	Santa Clara	California

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Finland,  Germany,  Israel,  Malaysia,  Peru,  Taiwan,  Thailand, 

References & Publications (1)

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 V1 — 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.	Up to Day 14 after each study 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).	Up to Day 14 after each study 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 6 months after Vaccination 4 (up to 19 months after Vaccination 1)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)