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

Pneumococcal Infections Clinical Trial

— PNEU-PED  

Official title:

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 in Healthy Infants (PNEU-PED)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03893448
• Other study ID #: V114-029
• Secondary ID: V114-0292018-004
• Status: Completed
• Phase: Phase 3
• Start date: June 19, 2019
• Est. completion date: May 24, 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1720
• Est. completion date: May 24, 2021
• Est. primary completion date: May 24, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 42 Days to 90 Days

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Pneumococcal Infections
• Pneumococcal Vaccines

Intervention

Biological:
• V114
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.
• Prevnar 13™
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.
• RotaTeq™
A total of 3 RotaTeq™ 2 mL oral dosings at ~2, ~4, and ~6 months of age.
• Pentacel™
A total of 3 Pentacel™ 0.5 mL IM dosings at ~2, ~4, and ~6 months of age.
• RECOMBIVAX HB™
A total of 3 RECOMBIVAX HB™ 0.5 mL IM dosings at ~2, ~4, and ~6 months of age.
• VAQTA™
One VAQTA™ 0.5 mL IM dosing at 12 to 15 months of age.
• MMR II™
One MMR II™ 0.5 mL subcutaneous (SC) dosing at 12 to 15 months of age.
• VARIVAX™
One VARIVAX™ 0.5 mL SC dosing at 12 to 15 months of age.
• HIBERIX™
One HIBERIX™ 0.5 mL IM dosing at Visit 5.

Locations

Country	Name	City	State
Puerto Rico	Cooperativa de Facultad Medica Sanacoop ( Site 0077)	Bayamon
Puerto Rico	Clinical Research of Puerto Rico ( Site 0075)	Guayama
Puerto Rico	CAIMED Center - Ponce School of Medicine ( Site 0076)	Ponce
Puerto Rico	San Juan Hospital ( Site 0079)	San Juan
Puerto Rico	University of Puerto Rico - Medical Science Campus ( Site 0078)	San Juan
Puerto Rico	Elba Antoniette Perez Vargas MD-Private Practice ( Site 0081)	Trujillo Alto
Thailand	Phramongkutklao Hospital ( Site 0033)	Bangkok
Thailand	Siriraj Hospital ( Site 0032)	Bangkok
Thailand	Maharaj Nakorn Chiang Mai Hospital ( Site 0030)	Chiang Mai
Thailand	Khon Kaen University ( Site 0031)	Muang	Khon Kaen
Turkey	Cukurova Uni Tip Fak Cocuk Sagligi ve Hasta ABD ( Site 0060)	Adana
Turkey	Ankara Universitesi Tip Fakultesi ( Site 0053)	Ankara
Turkey	Dokuz Eylul University Faculty of Medicine ( Site 0054)	Izmir
Turkey	Ege University Medical Faculty Hospital ( Site 0050)	Izmir
Turkey	Erciyes Universitesi Tip Fakultesi ( Site 0057)	Kayseri
United States	Advanced Clinical Research - Rancho Paseo ( Site 0163)	Banning	California
United States	Kentucky Pediatric/Adult Research Inc ( Site 0136)	Bardstown	Kentucky
United States	Altissima Clinical Research LLC ( Site 0213)	Bellflower	California
United States	Southland Clinical Research Center ( Site 0187)	Bellflower	California
United States	Alabama Clinical Therapeutics ( Site 0159)	Birmingham	Alabama
United States	Tufts Medical Center-Floating Hospital for Children ( Site 0129)	Boston	Massachusetts
United States	Advantage Clinical Trials ( Site 0274)	Bronx	New York
United States	Palmetto Pediatrics, PA ( Site 0164)	Charleston	South Carolina
United States	MultiCare Rockwood Cheney Clinic ( Site 0195)	Cheney	Washington
United States	Cheraw Pediatrics ( Site 0280)	Cheraw	South Carolina
United States	Senders Pediatrics ( Site 0190)	Cleveland	Ohio
United States	Haywood Pediatric and Adolescent Medicine Group ( Site 0248)	Clyde	North Carolina
United States	Davita Medical Group ( Site 0141)	Colorado Springs	Colorado
United States	DFW Clinical Research ( Site 0111)	Dallas	Texas
United States	Dayton Clinical Research ( Site 0188)	Dayton	Ohio
United States	Southeastern Pediatric Associates, P.A. ( Site 0107)	Dothan	Alabama
United States	Premier Health Research Center, LLC ( Site 0121)	Downey	California
United States	Pediatric Medical Associates ( Site 0239)	East Norriton	Pennsylvania
United States	Child Health Care Associates ( Site 0242)	East Syracuse	New York
United States	Allegheny Health & Wellness Pavilion West ( Site 0210)	Erie	Pennsylvania
United States	Pediatric Associates of Fall River ( Site 0183)	Fall River	Massachusetts
United States	Northwest Arkansas Pediatric Clinic ( Site 0172)	Fayetteville	Arkansas
United States	Lockman & Lubell Pediatrics ( Site 0166)	Fort Washington	Pennsylvania
United States	University of Texas Medical Branch ( Site 0185)	Galveston	Texas
United States	Parkside Pediatric ( Site 0125)	Greenville	South Carolina
United States	Cyn3rgy Research ( Site 0246)	Gresham	Oregon
United States	ACC Pediatric Research ( Site 0147)	Haughton	Louisiana
United States	CCP- Kid's Way ( Site 0130)	Hermitage	Pennsylvania
United States	Houston Clinical Research Network ( Site 0266)	Houston	Texas
United States	Pediatric Associates ( Site 0209)	Houston	Texas
United States	Ventavia Research Group LLC ( Site 0142)	Houston	Texas
United States	Children's Clinic of Jonesboro, PA ( Site 0184)	Jonesboro	Arkansas
United States	Children's Mercy Clinics on Broadway ( Site 0171)	Kansas City	Missouri
United States	Ventavia Research Group LLC ( Site 0139)	Keller	Texas
United States	Holston Medical Group ( Site 0165)	Kingsport	Tennessee
United States	FMC Science ( Site 0115)	Lampasas	Texas
United States	Wee Care Pediatrics ( Site 0154)	Layton	Utah
United States	University of Texas Medical Branch ( Site 0170)	League City	Texas
United States	Midwest Children's Health Research Institute, LLC ( Site 0106)	Lincoln	Nebraska
United States	Midwest Children's Health Research Institute, LLC ( Site 0109)	Lincoln	Nebraska
United States	Child Health Care Associates ( Site 0267)	Liverpool	New York
United States	DCOL Center for Clinical Research ( Site 0247)	Longview	Texas
United States	Medpharmics, LLC ( Site 0157)	Metairie	Louisiana
United States	Suncoast Research Associates, LLC ( Site 0250)	Miami	Florida
United States	Cottonwood Pediatrics ( Site 0153)	Murray	Utah
United States	Saltzer Medical Group ( Site 0215)	Nampa	Idaho
United States	Michael W Simon, MD., Pediatric & Adolescent Medicine ( Site 0276)	Nicholasville	Kentucky
United States	Suncoast Research Associates, LLC ( Site 0249)	North Miami Beach	Florida
United States	Kaiser Permanente Vaccine Study Center - Oakland ( Site 0282)	Oakland	California
United States	Children's Physicians, UNMC ( Site 0252)	Omaha	Nebraska
United States	South Alabama Pediatrics ( Site 0263)	Opp	Alabama
United States	MediSync Clinical Research Hattiesburg Clinic ( Site 0259)	Petal	Mississippi
United States	Pediatric Care ( Site 0138)	Provo	Utah
United States	Capitol Pediatrics & Adolescent Center ( Site 0223)	Raleigh	North Carolina
United States	Wee Care Pediatrics-Roy ( Site 0174)	Roy	Utah
United States	Kaiser Permanente - Sacramento ( Site 0257)	Sacramento	California
United States	Kaiser Permanente Vaccine Study Center - South Sacramento ( Site 0256)	Sacramento	California
United States	Dixie Pediatrics ( Site 0260)	Saint George	Utah
United States	University of Utah ( Site 0214)	Salt Lake City	Utah
United States	Kaiser Permanente - San Jose ( Site 0258)	San Jose	California
United States	Kaiser Permanente - Santa Clara ( Site 0244)	Santa Clara	California
United States	Southwest CARE Center ( Site 0161)	Santa Fe	New Mexico
United States	Virgo-Carter Pediatrics ( Site 0275)	Silver Spring	Maryland
United States	Multicare / Rockwood Clinic ( Site 0167)	Spokane	Washington
United States	Wee Care Pediatrics ( Site 0193)	Syracuse	Utah
United States	Children's Health Center ( Site 0272)	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Puerto Rico,  Thailand,  Turkey, 

References & Publications (1)

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, rando — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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™
Primary	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™
Primary	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)
Primary	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)
Primary	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)
Primary	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	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	Antibody responses to diphtheria toxoid, tetanus toxoid, and pertussis antigens were measured using Luminex Assay. The percentage of participants meeting specific criteria are summarized for each serotype. The serotype-specific response rate criteria are as follows: diphtheria toxoid: % =0.1 IU/mL; tetanus toxoid: % =0.1 IU/mL; pertussis toxin (PT): % = 5 EU/mL; pertussis filamentous hemagglutinin (FHA): % =5 EU/mL; pertussis fimbrae types 2/3 (FIM 2/3): % =20 EU/mL; pertussis pertactin (PRN): % =5 EU/mL; poliovirus 1: % neutralizing antibody (NAb) =1:8 dilution; poliovirus 2: % NAb =1:8 dilution, poliovirus 3: % NAb =1:8 dilution; and Haemophilus influenzae Type B polyribosylribitol phosphate (Hib-PRP): % =0.15 ug/mL.	One month after Vaccination 3 (Month 7)
Secondary	Pertussis Antigen Immunoglobulin G (IgG) Antibody (Ab) Geometric Mean Concentration (GMC) One Month After Vaccination 3	Pertussis antibody GMCs were measured using Luminex Assay.	One month after Vaccination 3 (Month 7)
Secondary	Hepatitis A Antibody Response Rate One Month After Vaccination 4	Antibody response rates to hepatitis A were measured with hepatitis A virus enzyme immunoassay (HAV EIA). The percentage of participants with hepatitis A antigen =10 mIU/mL are reported.	One month after Vaccination 4 (Month 13 to Month 16)
Secondary	Measles, Mumps, and Rubella Antibody Response Rate One Month After Vaccination 4	Antibody responses to measles were measured with the bulk measles IgG enzyme immunoassay (EIA). Antibody responses to mumps were measured with enzyme-linked immunosorbent assay (ELISA). Antibody responses to rubella were measured with Bulk Rubella IgG EIA. The percentage of participants with measles antigen =255 mIU/ML; mumps antigen =10 mumps Ab units/mL; and rubella antigen =10 IU/mL, are reported.	One month after Vaccination 4 (Month 13 to Month 16)
Secondary	Varicella-Zoster Virus (VZV) Antibody Response Rate One Month After Vaccination 4	Antibody responses to varicella-zoster virus were measured with glycoprotein enzyme-linked immunosorbent assay (gpELISA). The percentage of participants with VZV antigen =5 gpELISA units/mL are reported.	One month after Vaccination 4 (Month 13 to Month 16)
Secondary	Haemophilus Influenzae Type B Antibody Response Rate One Month After Vaccination 4	Antibody responses to Haemophilus influenzae Type B polyribosylribitol phosphate (Hib PRP) were measured with ELISA. The percentage of participants with anti-HiB PRP antigen =0.15 ug/mL are reported.	One month after Vaccination 4 (Month 13 to Month 16)
Secondary	Anti-Pneumococcal Polysaccharide (Anti-PnP) Serotype-Specific Immunoglobulin G (IgG) Geometric Mean Concentration (GMC) One Month After Vaccination 3 for 2 Unique V114 Seroptypes	Serotype-specific anti-PnP IgG GMCs for the 2 unique V114 serotypes were measured with PnECL. The GMCs for each serotype are reported.	One month after Vaccination 3 (Month 7)
Secondary	Anti-Pneumococcal Polysaccharide (Anti-PnP) Serotype-Specific Immunoglobulin G (IgG) Response Rates One Month After Vaccination 3 for 2 Unique V114 Seroptypes	Serotype-specific anti-PnP IgG response rates for the 2 unique V114 serotypes were measured with PnECL. The percentage of participants with IgG Ab =0.35 ug/mL are reported for each serotype.	One month after Vaccination 3 (Month 7)
Secondary	Anti-Pneumococcal Polysaccharide (Anti-PnP) Serotype-Specific Immunoglobulin G (IgG) Geometric Mean Concentrations (GMC) One Month After Vaccination 4 for 2 Unique V114 Seroptypes	Serotype-specific anti-PnP GMCs were measured with PnECL. The GMC for each serotype is reported.	One month after Vaccination 4 (Month 13 to Month 16)
Secondary	Anti-Pneumococcal Polysaccharide (Anti-PnP) Serotype-Specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT) One Month After Vaccination 3	Serotype-specific anti-PnP OPA GMTs were measured with multiplex opsonophagocytic assay (MOPA). The GMTs for each serotype are summarized.	One month after Vaccination 3 (Month 7)
Secondary	Anti-Pneumococcal Polysaccharide (Anti-PnP) Serotype-Specific Opsonophagocytic Activity (OPA) Response Rates One Month After Vaccination 3	Serotype-specific anti-PnP OPA GMTs were measured with MOPA. The percentage of participants meeting =0.35 ug/mL are reported for each serotype.	One month after Vaccination 3 (Month 7)
Secondary	Anti-Pneumococcal Polysaccharide (Anti-PnP) Serotype 3-Specific Immunoglobulin G (IgG) Response Rate One Month After Vaccination 3	Serotype 3-specific anti-PnP IgG response rates were measured with PnECL. The percentage of participants with IgG Ab =0.35 ug/mL are reported for Serotype 3.	One month after Vaccination 3 (Month 7)
Secondary	Anti-Pneumococcal Polysaccharide (Anti-PnP) Serotype 3-Specific Immunoglobulin G (IgG) Geometric Mean Concentration (GMC) One Month After Vaccination 3	Serotype 3-specific anti-PnP GMC was measured with PnECL.	One month after Vaccination 3 (Month 7)
Secondary	Anti-Pneumococcal Polysaccharide (Anti-PnP) Serotype 3-Specific Immunoglobulin G (IgG) Geometric Mean Concentration (GMC) One Month After Vaccination 4	Serotype 3-specific anti-PnP GMC were measured with PnECL.	One month after Vaccination 4 (Month 13 to Month 16)