Safety, Tolerability, and Immunogenicity of V114 in Healthy Infants (V114-029)

NCT03893448 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: V114-0292018-004109-21
• Study Type: interventional
• Target: 1,720
• Locations: 4 countries
• Sites: 81

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, and immunogenicity of V114 in healthy infants. The primary hypotheses are that: 1) V114 is non-inferior to Prevnar 13™ for the 13 shared serotypes between V114 and Prevnar 13™ based on response rates at 30 days following Dose 3; 2) V114 is non-inferior to Prevnar 13™ for the 2 unique V114 serotypes based on the response rate of the 2 unique V114 serotypes compared with the lowest response rate of any of the shared serotypes in Prevnar 13™, excluding serotype 3, at 30 days following Dose 3; 3) V114 is non-inferior to Prevnar 13™ for the 13 shared serotypes based on anti-pneumococcal polysaccharide (PnPs) serotype-specific immunoglobulin g (IgG) geometric mean concentrations (GMCs) at 30 days following Dose 3; 4) V114 is non-inferior to Prevnar 13™ for the 2 unique V114 serotypes based on the anti-PnPs serotype-specific IgG GMCs of the 2 unique V114 serotypes compared with the lowest IgG GMC of any of the shared serotypes in Prevnar 13™, excluding serotype 3, at 30 days following Dose 3; 5) V114 is non-inferior to Prevnar 13™ for the 13 shared serotypes between V114 and Prevnar 13™ based on anti-PnPs serotype-specific IgG GMCs at 30 days following Dose 4; and 6) V114 is non-inferior to Prevnar 13™ for the 2 unique V114 serotypes based on anti-PnPs serotype-specific IgG GMCs of the 2 unique V114 serotypes compared with the lowest IgG GMC of any of the shared serotypes in Prevnar 13, excluding serotype 3, at 30 days following Dose 4.

Conditions

Pneumococcal Infections; Pneumococcal Vaccines

Outcome Measures

Primary Outcomes (6)

• Percentage of Participants With Solicited Injection-Site Adverse Events (AEs) in V114 Versus Prevnar 13™

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Solicited injection-site AEs consisted of swelling, redness, pain or tenderness, and hard lump.

  Up to 14 days after each vaccination with either V114 or Prevnar 13™

• Percentage of Participants With Solicited Systemic AEs

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Solicited systemic AEs consisted of irritability, drowsiness, appetite lost, and hives or welts.

  Up to 14 days after each vaccination with either V114 or Prevnar 13™

• Percentage of Participants With Vaccine-Related Serious Adverse Events (SAEs)

  An SAE is any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires inpatient hospitalization or prolongs existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an other important medical event. Any SAEs that are at least possibly related to vaccination are summarized.

  From Day 1 up to 6 months after Vaccination 4 (up to 21 months)

• Percentage of Participants With Anti-Pneumococcal Polysaccharide (Anti-PnP) Immunoglobulin G (IgG) Antibody (Ab) ≥0.35 ug/mL One Month After Vaccination 3

  Anti-PnP serotype-specific IgG response rates for the 15 serotypes contained in V114 were measured with pneumococcal electrochemiluminescence (PnECL). The percentage of participants with IgG Ab ≥0.35 ug/mL are reported for each serotype.

  One month after Vaccination 3 (Month 7)

• Geometric Mean Concentration (GMC) of Anti-PnP IgG Ab One Month After Vaccination 3

  The GMC of anti-PnP IgG Ab were measured with PnECL one month after vaccination 3 and reported for the 15 serotypes contained in V114. IgG GMCs were compared to the lowest in recipients of Prevnar 13™ excluding serotype 3 for the 2 serotypes unique to V114, and compared to the same serotypes for the 13 shared serotypes.

  One month after Vaccination 3 (Month 7)

• GMC of Anti-PnP IgG Ab One Month After Vaccination 4

  The GMC of anti-PnP IgG Ab were measured with PnECL one month after vaccination 4 and reported for the 15 serotypes contained in V114. IgG GMCs were compared to the lowest in recipients of Prevnar 13™ excluding serotype 3 for the 2 serotypes unique to V114, and compared to the same serotypes for the 13 shared serotypes.

  One month after Vaccination 4 (Month 13 to Month 16)

Secondary Outcomes (14)

• Percentage of Participants Meeting Response Rate Criteria for Pentacel™-Specific (Anti-Diptheria Toxoid, Tetanus Toxoid, and Pertussis Antigens) Immunoglobulin G (IgG) Antibody (Ab) Geometric Mean Concentration (GMC) One Month After Vaccination 3

  One month after Vaccination 3 (Month 7)

• Pertussis Antigen Immunoglobulin G (IgG) Antibody (Ab) Geometric Mean Concentration (GMC) One Month After Vaccination 3

  One month after Vaccination 3 (Month 7)

• Hepatitis A Antibody Response Rate One Month After Vaccination 4

  One month after Vaccination 4 (Month 13 to Month 16)

• Measles, Mumps, and Rubella Antibody Response Rate One Month After Vaccination 4

  One month after Vaccination 4 (Month 13 to Month 16)

• Varicella-Zoster Virus (VZV) Antibody Response Rate One Month After Vaccination 4

  One month after Vaccination 4 (Month 13 to Month 16)

Study Arms (2)

V114

EXPERIMENTAL

Participants receive 4 total 0.5 mL intramuscular (IM) vaccinations at \~2, 4, 6, and 12 to 15 months of age. Participants will receive other vaccinations (i.e., RotaTeq™, Pentacel™, RECOMBIVAX HB™, VAQTA™, M-M-R II™, VARIVAX™, and HIBERIX™) as part of their vaccination schedule.

Biological: V114; Biological: RotaTeq™; Biological: Pentacel™; Biological: RECOMBIVAX HB™; Biological: VAQTA™; Biological: MMR II™; Biological: VARIVAX™; Biological: HIBERIX™

Prevnar 13™

ACTIVE COMPARATOR

Participants receive 4 total 0.5 mL IM vaccinations at \~2, 4, 6, and 12 to 15 months of age. Participants will also receive other vaccines (i.e., RotaTeq™, Pentacel™, RECOMBIVAX HB™, VAQTA™, M-M-R II™, VARIVAX™, and HIBERIX™) as part of their vaccination schedule.

Biological: Prevnar 13™; Biological: RotaTeq™; Biological: Pentacel™; Biological: RECOMBIVAX HB™; Biological: VAQTA™; Biological: MMR II™; Biological: VARIVAX™; Biological: HIBERIX™

Interventions

V114 BIOLOGICAL

V114 15-valent pneumococcal conjugate vaccine containing 13 serotypes present in Prevnar 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.

Also known as: VAXNEUVANCE™, Pneumococcal 15-Valent Conjugate Vaccine

V114

Prevnar 13™ BIOLOGICAL

Prevnar 13™ 13-valent pneumococcal conjugate vaccine containing 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) in each 0.5 mL IM administration.

Prevnar 13™

RotaTeq™ BIOLOGICAL

A total of 3 RotaTeq™ 2 mL oral dosings at \~2, \~4, and \~6 months of age.

Prevnar 13™; V114

Pentacel™ BIOLOGICAL

A total of 3 Pentacel™ 0.5 mL IM dosings at \~2, \~4, and \~6 months of age.

Prevnar 13™; V114

RECOMBIVAX HB™ BIOLOGICAL

A total of 3 RECOMBIVAX HB™ 0.5 mL IM dosings at \~2, \~4, and \~6 months of age.

Prevnar 13™; V114

VAQTA™ BIOLOGICAL

One VAQTA™ 0.5 mL IM dosing at 12 to 15 months of age.

Prevnar 13™; V114

MMR II™ BIOLOGICAL

One MMR II™ 0.5 mL subcutaneous (SC) dosing at 12 to 15 months of age.

Prevnar 13™; V114

VARIVAX™ BIOLOGICAL

One VARIVAX™ 0.5 mL SC dosing at 12 to 15 months of age.

Prevnar 13™; V114

HIBERIX™ BIOLOGICAL

One HIBERIX™ 0.5 mL IM dosing at Visit 5.

Prevnar 13™; V114

Eligibility Criteria

• Age: 42 Days - 90 Days
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Is healthy (based on a review of medical history and physical examination) in the clinical judgement of the investigator
• 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.

You may not qualify if:

• Has a 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 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.
• Had a recent febrile illness (rectal temperature ≥38.1°C \[=100.5°F\] or axillary temperature ≥37.8°C \[=100.0°F\]) occurring within 72 hours prior to receipt of study vaccine.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (81)

Alabama Clinical Therapeutics ( Site 0159)

Birmingham, Alabama, 35205, United States

Location

Southeastern Pediatric Associates, P.A. ( Site 0107)

Dothan, Alabama, 36305, United States

Location

South Alabama Pediatrics ( Site 0263)

Opp, Alabama, 36467, United States

Location

Northwest Arkansas Pediatric Clinic ( Site 0172)

Fayetteville, Arkansas, 72703, United States

Location

Children's Clinic of Jonesboro, PA ( Site 0184)

Jonesboro, Arkansas, 72401, United States

Location

Advanced Clinical Research - Rancho Paseo ( Site 0163)

Banning, California, 92220, United States

Location

Altissima Clinical Research LLC ( Site 0213)

Bellflower, California, 90706, United States

Location

Southland Clinical Research Center ( Site 0187)

Bellflower, California, 90706, United States

Location

Premier Health Research Center, LLC ( Site 0121)

Downey, California, 90240, United States

Location

Kaiser Permanente Vaccine Study Center - Oakland ( Site 0282)

Oakland, California, 94612, United States

Location

Kaiser Permanente - Sacramento ( Site 0257)

Sacramento, California, 95815, United States

Location

Kaiser Permanente Vaccine Study Center - South Sacramento ( Site 0256)

Sacramento, California, 95823, United States

Location

Kaiser Permanente - San Jose ( Site 0258)

San Jose, California, 95119, United States

Location

Kaiser Permanente - Santa Clara ( Site 0244)

Santa Clara, California, 95051, United States

Location

Davita Medical Group ( Site 0141)

Colorado Springs, Colorado, 80922, United States

Location

Suncoast Research Associates, LLC ( Site 0250)

Miami, Florida, 33184, United States

Location

Suncoast Research Associates, LLC ( Site 0249)

North Miami Beach, Florida, 33160, United States

Location

Children's Health Center ( Site 0272)

Tampa, Florida, 33617, United States

Location

Saltzer Medical Group ( Site 0215)

Nampa, Idaho, 83686, United States

Location

Kentucky Pediatric/Adult Research Inc ( Site 0136)

Bardstown, Kentucky, 40004, United States

Location

Michael W Simon, MD., Pediatric & Adolescent Medicine ( Site 0276)

Nicholasville, Kentucky, 40356, United States

Location

ACC Pediatric Research ( Site 0147)

Haughton, Louisiana, 71037, United States

Location

Medpharmics, LLC ( Site 0157)

Metairie, Louisiana, 70006, United States

Location

Virgo-Carter Pediatrics ( Site 0275)

Silver Spring, Maryland, 20910, United States

Location

Tufts Medical Center-Floating Hospital for Children ( Site 0129)

Boston, Massachusetts, 02111, United States

Location

Pediatric Associates of Fall River ( Site 0183)

Fall River, Massachusetts, 02721, United States

Location

MediSync Clinical Research Hattiesburg Clinic ( Site 0259)

Petal, Mississippi, 39465, United States

Location

Children's Mercy Clinics on Broadway ( Site 0171)

Kansas City, Missouri, 64111, United States

Location

Midwest Children's Health Research Institute, LLC ( Site 0109)

Lincoln, Nebraska, 68505, United States

Location

Midwest Children's Health Research Institute, LLC ( Site 0106)

Lincoln, Nebraska, 68522, United States

Location

Children's Physicians, UNMC ( Site 0252)

Omaha, Nebraska, 68198, United States

Location

Southwest CARE Center ( Site 0161)

Santa Fe, New Mexico, 87501, United States

Location

Child Health Care Associates ( Site 0242)

East Syracuse, New York, 13057, United States

Location

Child Health Care Associates ( Site 0267)

Liverpool, New York, 13090, United States

Location

Advantage Clinical Trials ( Site 0274)

The Bronx, New York, 10468, United States

Location

Haywood Pediatric and Adolescent Medicine Group ( Site 0248)

Clyde, North Carolina, 28721, United States

Location

Capitol Pediatrics & Adolescent Center ( Site 0223)

Raleigh, North Carolina, 27609, United States

Location

Senders Pediatrics ( Site 0190)

Cleveland, Ohio, 44121, United States

Location

Dayton Clinical Research ( Site 0188)

Dayton, Ohio, 45406, United States

Location

Cyn3rgy Research ( Site 0246)

Gresham, Oregon, 97030, United States

Location

Pediatric Medical Associates ( Site 0239)

East Norriton, Pennsylvania, 19401, United States

Location

Allegheny Health & Wellness Pavilion West ( Site 0210)

Erie, Pennsylvania, 16506, United States

Location

Lockman & Lubell Pediatrics ( Site 0166)

Fort Washington, Pennsylvania, 19034, United States

Location

CCP- Kid's Way ( Site 0130)

Hermitage, Pennsylvania, 16148, United States

Location

Palmetto Pediatrics, PA ( Site 0164)

Charleston, South Carolina, 29406-9170, United States

Location

Cheraw Pediatrics ( Site 0280)

Cheraw, South Carolina, 29520, United States

Location

Parkside Pediatric ( Site 0125)

Greenville, South Carolina, 29607, United States

Location

Holston Medical Group ( Site 0165)

Kingsport, Tennessee, 37660, United States

Location

DFW Clinical Research ( Site 0111)

Dallas, Texas, 75234, United States

Location

University of Texas Medical Branch ( Site 0185)

Galveston, Texas, 77555, United States

Location

Ventavia Research Group LLC ( Site 0142)

Houston, Texas, 77008, United States

Location

Pediatric Associates ( Site 0209)

Houston, Texas, 77087, United States

Location

Houston Clinical Research Network ( Site 0266)

Houston, Texas, 77090, United States

Location

Ventavia Research Group LLC ( Site 0139)

Keller, Texas, 76248, United States

Location

FMC Science ( Site 0115)

Lampasas, Texas, 76550, United States

Location

University of Texas Medical Branch ( Site 0170)

League City, Texas, 77573, United States

Location

DCOL Center for Clinical Research ( Site 0247)

Longview, Texas, 75605, United States

Location

Wee Care Pediatrics ( Site 0154)

Layton, Utah, 84041, United States

Location

Cottonwood Pediatrics ( Site 0153)

Murray, Utah, 84107, United States

Location

Pediatric Care ( Site 0138)

Provo, Utah, 84604, United States

Location

Wee Care Pediatrics-Roy ( Site 0174)

Roy, Utah, 84067, United States

Location

University of Utah ( Site 0214)

Salt Lake City, Utah, 84113, United States

Location

Dixie Pediatrics ( Site 0260)

St. George, Utah, 84790, United States

Location

Wee Care Pediatrics ( Site 0193)

Syracuse, Utah, 84075, United States

Location

MultiCare Rockwood Cheney Clinic ( Site 0195)

Cheney, Washington, 99004, United States

Location

Multicare / Rockwood Clinic ( Site 0167)

Spokane, Washington, 99202, United States

Location

Cooperativa de Facultad Medica Sanacoop ( Site 0077)

Bayamón, 00961, Puerto Rico

Location

Clinical Research of Puerto Rico ( Site 0075)

Guayama, 00784, Puerto Rico

Location

CAIMED Center - Ponce School of Medicine ( Site 0076)

Ponce, 00716, Puerto Rico

Location

San Juan Hospital ( Site 0079)

San Juan, 00935, Puerto Rico

Location

University of Puerto Rico - Medical Science Campus ( Site 0078)

San Juan, 00935, Puerto Rico

Location

Elba Antoniette Perez Vargas MD-Private Practice ( Site 0081)

Trujillo Alto, 00976, Puerto Rico

Location

Khon Kaen University ( Site 0031)

Muang, Changwat Khon Kaen, 40002, Thailand

Location

Phramongkutklao Hospital ( Site 0033)

Bangkok, 10400, Thailand

Location

Siriraj Hospital ( Site 0032)

Bangkok, 10700, Thailand

Location

Maharaj Nakorn Chiang Mai Hospital ( Site 0030)

Chiang Mai, 50200, Thailand

Location

Cukurova Uni Tip Fak Cocuk Saglıgı ve Hasta ABD ( Site 0060)

Adana, 01330, Turkey (Türkiye)

Location

Ankara Universitesi Tip Fakultesi ( Site 0053)

Ankara, 06590, Turkey (Türkiye)

Location

Ege University Medical Faculty Hospital ( Site 0050)

Izmir, 35040, Turkey (Türkiye)

Location

Dokuz Eylul University Faculty of Medicine ( Site 0054)

Izmir, 35340, Turkey (Türkiye)

Location

Erciyes Universitesi Tip Fakultesi ( Site 0057)

Kayseri, 38039, Turkey (Türkiye)

Location

Related Publications (2)

• Lupinacci R, Rupp R, Wittawatmongkol O, Jones J, Quinones J, Ulukol B, Dagan R, Richmond P, Stek JE, Romero L, Koseoglu S, Tamms G, McFetridge R, Li J, Cheon K, Musey L, Banniettis N, Bickham K; V114-029 PNEU-PED study group. A phase 3, multicenter, randomized, double-blind, active-comparator-controlled study to evaluate the safety, tolerability, and immunogenicity of a 4-dose regimen of V114, a 15-valent pneumococcal conjugate vaccine, in healthy infants (PNEU-PED). Vaccine. 2023 Jan 27;41(5):1142-1152. doi: 10.1016/j.vaccine.2022.12.054. Epub 2023 Jan 6.

  PMID: 36621410 RESULT

• Mt-Isa S, Chumbley JR, Crawford EL, Banniettis N, Buchwald UK, Weaver J, Weiss T. An indirect treatment comparison (ITC) and matching-adjusted indirect comparison (MAIC) between a 15-valent (V114) and a 20-valent (PCV20) pneumococcal conjugate vaccine among healthy infants. Expert Rev Vaccines. 2023 Jan-Dec;22(1):906-917. doi: 10.1080/14760584.2023.2270039. Epub 2023 Oct 19.

  PMID: 37846456 DERIVED

MeSH Terms

Conditions

Pneumococcal Infections

Interventions

13-valent pneumococcal vaccine; RotaTeq; pentacel; Recombivax HB; Hepatitis A Vaccines; Chickenpox Vaccine; Hiberix

Condition Hierarchy (Ancestors)

Streptococcal Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Viral Hepatitis Vaccines; Viral Vaccines; Vaccines; Biological Products; Complex Mixtures; Herpesvirus Vaccines

Results Point of Contact

• Title: Clinical Trials Disclosure
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2019
• First Posted: March 28, 2019
• Study Start: June 19, 2019
• Primary Completion: May 24, 2021
• Study Completion: May 24, 2021
• Last Updated: July 28, 2023
• Results First Posted: March 25, 2022

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will share

Locations

TU (5); TH (4); US (66); PR (6)