Safety, Tolerability, and Immunogenicity of V419 Given Concomitantly With Prevnar 13™ and RotaTeq™ (V419-005)

A Phase III Randomized, Open-Label, Active-Comparator Controlled Clinical Study to Evaluate the Safety, Tolerability, and Immunogenicity of V419 in Infants When Given at 2, 4, and 6 Months Concomitantly With Prevnar 13™ and RotaTeq™

This is a study to assess the safety, tolerability, and immunogenicity of V419 (PR5I) when administered as an infant series at 2, 4, and 6 months of age followed by a toddler dose of DAPTACEL™, Prevnar 13™ and PedvaxHIB™ at 15 months of age. The study will determine whether subjects who receive V419 have a similar immune response to the vaccine compared to subjects who receive licensed component vaccine controls.

Study Overview

• Status: Completed
• Conditions: Virus Diseases; Bacterial Infections
• Intervention / Treatment: Biological: V419; Biological: DAPTACEL™; Biological: PedvaxHIB™; Biological: Prevnar 13™; Biological: RotaTeq™; Biological: PENTACEL™; Biological: Recombivax HB vaccine; Biological: ActHIB™

• Study Type: Interventional
• Enrollment (Actual): 1473
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria :

• Participant is a healthy infant
• Participant has received one dose of monovalent hepatitis B vaccine prior to or at 1 month of age

Exclusion Criteria :

• Participant has received more than one dose of monovalent hepatitis B vaccine or hepatitis B based combination vaccine prior to study entry
• Participant has been vaccinated with any acellular pertussis or whole cell pertussis based combination vaccines, haemophilus influenzae type b conjugate, poliovirus, pneumococcal conjugate or pneumococcal polysaccharide, rotavirus, or any combination of the above
• Participant has had a fever ≥38.0°C (≥110.4°F) within 24 hours of study enrollment
• Participant was vaccinated with any non-study vaccine (i.e., inactivated, conjugated, live virus vaccine) within 30 days prior to study enrollment, except for inactivated influenza vaccine which will be permitted 15 days or more prior to enrollment
• Participant has hepatitis B surface antigen (HBsAg) seropositivity (by medical history)
• Participant has a history of haemophilus influenzae type B, hepatitis B, diphtheria, tetanus, pertussis, poliomyelitis, rotavirus, or pneumococcal infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: V419; V419 0.5 mL intramuscular injection (IM) at 2, 4, and 6 months of age; Daptacel™ 0.5 mL IM at 15 months of age; PedvaxHIB™ 0.5 mL IM at 15 months of age; Prevnar 13™ 0.5 mL IM at 2, 4, 6, and 15 months of age; and RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age.	Biological: V419; V419 (Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus, Haemophilus b Conjugate [Meningococcal Outer Membrane Protein Complex], and Hepatitis B [Recombinant] Vaccine) 0.5 mL intramuscular injection at 2, 4, and 6 months of age; Biological: DAPTACEL™; DAPTACEL™ 0.5 mL intramuscular injection at 15 months of age; Biological: PedvaxHIB™; PedvaxHIB™ 0.5 mL intramuscular injection at 15 months of age; Biological: Prevnar 13™; Prevnar 13™ 0.5 mL intramuscular injection at 2, 4, 6, and 15 months of age; Biological: RotaTeq™; RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age; Other Names: V260
ACTIVE_COMPARATOR: Control; Pentacel™ 0.5 mL IM at 2, 4, and 6 months of age; Recombivax HB vaccine 0.5 mL IM at 2 and 6 months of age; Daptacel™ 0.5 mL IM at 15 months of age; ActHIB™ 0.5 mL IM at 15 months of age; Prevnar 13™ 0.5 mL IM at 2, 4, 6, and 15 months of age; and RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age.	Biological: DAPTACEL™; DAPTACEL™ 0.5 mL intramuscular injection at 15 months of age; Biological: Prevnar 13™; Prevnar 13™ 0.5 mL intramuscular injection at 2, 4, 6, and 15 months of age; Biological: RotaTeq™; RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age; Other Names: V260; Biological: PENTACEL™; PENTACEL™ 0.5 mL intramuscular injection at 2, 4, and 6 months of age; Biological: Recombivax HB vaccine; Recombivax HB vaccine 0.5 mL intramuscular injection at 2 and 6 months of age; Biological: ActHIB™; ActHIB™ 0.5 mL intramuscular injection at 15 months of age

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Responding to Polyribosylribitol Phosphate Antigen	Participant serum samples were collected for testing with a radioimmunoassay for antibodies to Haemophilus influenza type b capsular polysaccharide polyribosylribitol phosphate. Response was evaluated for titer >=0.15 μg/mL and >=1.0 μg/mL.	Postdose 3 (Month 7)
Percentage of Participants Responding to Hepatitis B Surface Antigen	Participant serum samples were collected for testing with an enhanced chemiluminescence assay for antibodies to Hepatitis B Surface Antigen. Response was defined as a titer >=10 milli International units (mIU)/mL.	Postdose 3 (Month 7)
Percentage of Participants Responding to Diphtheria Toxin	Participant serum samples were collected for testing with a Micrometabolic Inhibition Test for neutralizing antibodies to diphtheria toxin. Response was defined as a titer >=0.1 International unit (IU)/mL.	Postdose 3 (Month 7)
Percentage of Participants Responding to Tetanus Toxin	Participant serum samples were collected for testing with an ELISA for anti-tetanus antibodies. Response was defined as a titer >=0.1 IU/mL.	Postdose 3 (Month 7)
Percentage of Participants Responding to Pertussis Toxin	Participant serum samples were collected for testing with an Enzyme-linked Immunosorbent Assay (ELISA) for antibodies to pertussis toxin. Response was defined as follows: 1) if the predose titer was <4 times the lower limit of quantitation (4X LLOQ) then the postdose titer was >=4X LLOQ; 2) if the predose titer was >=4X LLOQ then the postdose titer was >= the predose titer.	Postdose 3 (Month 7)
Percentage of Participants Responding to Pertussis Filamentous Hemagglutinin	Participant serum samples were collected for testing with an ELISA for antibodies to pertussis filamentous hemagglutinin. Response was defined as follows: 1) if the predose titer was <4X LLOQ then the postdose titer was >=4X LLOQ; 2) if the predose titer was >=4X LLOQ then the postdose titer was >= the predose titer.	Postdose 3 (Month 7)
Percentage of Participants Responding to Pertussis Pertactin	Participant serum samples were collected for testing with an ELISA for antibodies to pertussis pertactin. Response was defined as follows: 1) if the predose titer was <4X LLOQ then the postdose titer was >=4X LLOQ; 2) if the predose titer was >=4X LLOQ then the postdose titer was >= the predose titer.	Postdose 3 (Month 7)
Percentage of Participants Responding to Pertussis Fimbriae	Participant serum samples were collected for testing with an ELISA for antibodies to pertussis fimbriae. Response was defined as follows: 1) if the predose titer was <4X LLOQ then the postdose titer was >=4X LLOQ; 2) if the predose titer was >=4X LLOQ then the postdose titer was >= the predose titer.	Postdose 3 (Month 7)
Percentage of Participants Responding to Poliovirus Type 1	Participant serum samples were collected for testing with a Micrometabolic Inhibition Test for neutralizing antibodies to Poliovirus Type 1. Response is defined as a titer >=8.	Postdose 3 (Month 7)
Percentage of Participants Responding to Poliovirus Type 2	Participant serum samples were collected for testing with a Micrometabolic Inhibition Test for neutralizing antibodies to Poliovirus Type 2. Response is defined as a titer >=8.	Postdose 3 (Month 7)
Percentage of Participants Responding to Poliovirus Type 3	Participant serum samples were collected for testing with a Micrometabolic Inhibition Test for neutralizing antibodies to Poliovirus Type 3. Response is defined as a titer >=8.	Postdose 3 (Month 7)
Geometric Mean Concentration of Antibodies to Pertussis Toxin	Participant serum samples were collected for testing with an ELISA for antibodies to pertussis toxin. The unit of measure is ELISA units/mL (EU/mL).	Postdose 3 (Month 7)
Geometric Mean Concentration of Antibodies to Pertussis Filamentous Hemagglutinin	Participant serum samples were collected for testing with an ELISA for antibodies to pertussis filamentous hemagglutinin.	Postdose 3 (Month 7)
Geometric Mean Concentration of Antibodies to Pertussis Pertactin	Participant serum samples were collected for testing with an ELISA for antibodies to pertussis pertactin.	Postdose 3 (Month 7)
Geometric Mean Concentration of Antibodies to Pertussis Fimbriae	Participant serum samples were collected for testing with an ELISA for antibodies to pertussis fimbriae.	Postdose 3 (Month 7)
Percentage of Participants Responding to Pertussis Toxin	Participant serum samples were collected for testing with an ELISA for antibodies to pertussis toxin. Response was defined as follows: 1) if the predose titer was <4 times the lower limit of quantitation (4X LLOQ) then the postdose titer was >=4X LLOQ; 2) if the predose titer was >=4X LLOQ then the postdose titer was >= the predose titer.	Postdose 4 (Month 16)
Percentage of Participants Responding to Pertussis Filamentous Hemagglutinin	Participant serum samples were collected for testing with an ELISA for antibodies to pertussis filamentous hemagglutinin. Response was defined as follows: 1) if the predose titer was <4 times the lower limit of quantitation (4X LLOQ) then the postdose titer was >=4X LLOQ; 2) if the predose titer was >=4X LLOQ then the postdose titer was >= the predose titer.	Postdose 4 (Month 16)
Percentage of Participants Responding to Pertussis Pertactin	Participant serum samples were collected for testing with an ELISA for antibodies to pertussis pertactin. Response was defined as follows: 1) if the predose titer was <4 times the lower limit of quantitation (4X LLOQ) then the postdose titer was >=4X LLOQ; 2) if the predose titer was >=4X LLOQ then the postdose titer was >= the predose titer.	Postdose 4 (Month 16)
Percentage of Participants Responding to Pertussis Fimbriae	Participant serum samples were collected for testing with an ELISA for antibodies to pertussis fimbriae. Response was defined as follows: 1) if the predose titer was <4 times the lower limit of quantitation (4X LLOQ) then the postdose titer was >=4X LLOQ; 2) if the predose titer was >=4X LLOQ then the postdose titer was >= the predose titer.	Postdose 4 (Month 16)
Geometric Mean Concentration of Antibodies to Pertussis Toxin	Participant serum samples were collected for testing with an ELISA for antibodies to pertussis toxin.	Postdose 4 (Month 16)
Geometric Mean Concentration of Antibodies to Pertussis Filamentous Hemagglutinin	Participant serum samples were collected for testing with an ELISA for antibodies to pertussis filamentous hemagglutinin.	Postdose 4 (Month 16)
Geometric Mean Concentration of Antibodies to Pertussis Pertactin	Participant serum samples were collected for testing with an ELISA for antibodies to pertussis pertactin.	Postdose 4 (Month 16)
Geometric Mean Concentration of Antibodies to Pertussis Fimbriae	Participant serum samples were collected for testing with an ELISA for antibodies to pertussis fimbriae.	Postdose 4 (Month 16)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Concentration of Antibodies to Polyribosylribitol Phosphate Antigen	Participant serum samples were collected for testing with a radioimmunoassay for antibodies to Haemophilus influenza type b capsular polysaccharide polyribosylribitol phosphate.	Postdose 3 (Month 7)
Geometric Mean Concentration of Immunoglobulin A (IgA) Antibodies to Rotavirus	Participant serum samples were collected for testing with an Enzyme-linked Immunosorbent assay for IgA antibodies to rotavirus.	Postdose 3 (Month 7)
Percentage of Participants Reporting Solicited Injection-site or Systemic Reactions	Solicited injection-site reactions: Pain, Erythema, and Swelling. Solicited systemic reactions: Pyrexia, Vomiting, Crying abnormal, Somnolence, Decreased appetite, and Irritability. Grade 3 Solicited injection site reaction: Pain, Cries when injected limb is moved or the movement of the injected limb is reduced; Erythema and Swelling, >5 cm. Grade 3 Solicited systemic reactions: Pyrexia, >=39.5°C (>=103.1°F) rectal; Vomiting, >=6 episodes per 24 hours or requiring parenteral hydration; Crying abnormal, >3 hours; Somnolence, Sleeping most of the time or difficult to wake up; Decreased appetite, Refuses >=3 feeds or refuses most feeds; Irritability, Inconsolable.	Up to 5 days after any infant vaccination (up to 6 months)
Percentage of Participants Reporting One or More Solicited Adverse Events Related to Study Drug	Solicited systemic adverse events: pyrexia, vomiting, crying abnormal, somnolence, decreased appetite, and irritability. Adverse events deemed related to study drug were those judged to be definitely related, probably related, or possibly related by the investigator.	Up to 5 days after any infant vaccination (up to 6 months)
Percentage of Participants Reporting One or More Solicited Adverse Events Related to Study Drug	Solicited systemic adverse events: pyrexia, vomiting, crying abnormal, somnolence, decreased appetite, and irritability. Adverse events deemed related to study drug were those judged to be definitely related, probably related, or possibly related by the investigator.	Up to 5 days after each infant vaccination (up to 6 months)
Percentage of Participants With Elevated Temperature by Severity	Maximum temperature (all routes) was based on actual temperatures recorded with no adjustments to the measurement route. Maximum temperature (rectal) was required of all participants if the reading by another method was >=38.0°C.	Up to 5 days after any infant vaccination (up to 6 months)
Percentage of Participants With Pyrexia, Febrile Convulsion, or Convulsion	The percentage of participants with one or more adverse events (AE), serious adverse events (SAE), and vaccine-related SAE (pyrexia, febrile convulsion, and convulsion) is reported.	Up to 15 days after any infant vaccination (up to 6 months)
Percentage of Participants With Pyrexia, Febrile Convulsion, or Convulsion	The percentage of participants with one or more adverse events (AE), serious adverse events (SAE), and vaccine-related SAE (pyrexia, febrile convulsion, and convulsion) is reported.	Up to 181 days after any infant vaccination (up to 12 months)

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Collaborators: MCM Vaccines B.V.

Publications and helpful links

General Publications

• Marshall GS, Adams GL, Leonardi ML, Petrecz M, Flores SA, Ngai AL, Xu J, Liu G, Stek JE, Foglia G, Lee AW. Immunogenicity, Safety, and Tolerability of a Hexavalent Vaccine in Infants. Pediatrics. 2015 Aug;136(2):e323-32. doi: 10.1542/peds.2014-4102.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 19, 2011
• Primary Completion (ACTUAL): May 9, 2013
• Study Completion (ACTUAL): May 9, 2013

Study Registration Dates

• First Submitted: April 15, 2011
• First Submitted That Met QC Criteria: April 15, 2011
• First Posted (ESTIMATE): April 18, 2011

Study Record Updates

• Last Update Posted (ACTUAL): November 15, 2018
• Last Update Submitted That Met QC Criteria: October 19, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Diphtheria; Tetanus; Poliomyelitis; Haemophilus influenzae type b infection; Whooping Cough (pertussis); Hepatitis B infection
• Additional Relevant MeSH Terms: Bacterial Infections and Mycoses; Infections; Virus Diseases; Bacterial Infections; Physiological Effects of Drugs; Immunologic Factors; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: V419-005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf