A Study of V419 Given Concomitantly With Prevnar 13™ and RotaTeq™ (V419-006)

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

This study will determine whether three manufacturing lots of V419 (PR5I) induce similar immune responses to all of the antigens contained in V419 when given concomitantly with Prevnar13™ and RotaTeq™.

Study Overview

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

Detailed Description

This study is partially Double-Blinded in that the participants' parents/guardians, investigator/study site personnel, and Sponsor's representatives will be blinded to the lot of V419 the participant is randomized to receive, but not to the participant's treatment group (V419 or control).

• Study Type: Interventional
• Enrollment (Actual): 2808
• 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 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, measles, mumps, rubella, or varicella vaccines or any combination of the above
• Participant has had an illness with fever within 24 hours of study enrollment
• Participant was vaccinated with any non-study vaccine (i.e. inactivated, conjugated or live virus vaccine within 30 days prior to enrollment, except for inactivated influenza vaccine, which is permitted 15 days or more prior to enrollment
• Participant or his/her mother 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 Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: V419 Lot A; V419 (Lot A) 0.5 mL intramuscular injection (IM) at 2, 4, and 6 months of age; Pentacel™ 0.5 mL IM at 15 month 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: 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; 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) (from one of three lots) 0.5 mL intramuscular injection at 2, 4, and 6 months of age.; Biological: PENTACEL™; PENTACEL™ 0.5 mL intramuscular injection at 15 months of age in the V419 groups and at 2, 4, 6, and 15 months of age in the control group
Experimental: V419 Lot B; V419 (Lot B) 0.5 mL IM at 2, 4, and 6 months of age; Pentacel™ 0.5 mL IM at 15 month 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: 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; 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) (from one of three lots) 0.5 mL intramuscular injection at 2, 4, and 6 months of age.; Biological: PENTACEL™; PENTACEL™ 0.5 mL intramuscular injection at 15 months of age in the V419 groups and at 2, 4, 6, and 15 months of age in the control group
Experimental: V419 Lot C; V419 (Lot C) 0.5 mL IM at 2, 4, and 6 months of age; Pentacel™ 0.5 mL IM at 15 month 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: 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; 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) (from one of three lots) 0.5 mL intramuscular injection at 2, 4, and 6 months of age.; Biological: PENTACEL™; PENTACEL™ 0.5 mL intramuscular injection at 15 months of age in the V419 groups and at 2, 4, 6, and 15 months of age in the control group
Active Comparator: Control; Pentacel™ 0.5 mL IM at 2, 4, 6, and 15 months of age; Prevnar 13™ 0.5 mL IM at 2, 4, 6, and 15 months of age; RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age; and Recombivax HB vaccine 0.5 mL IM at 2 and 6 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; Biological: Recombivax HB vaccine; Recombivax HB vaccine 0.5 mL intramuscular injection at 2 and 6 months of age; Biological: PENTACEL™; PENTACEL™ 0.5 mL intramuscular injection at 15 months of age in the V419 groups and at 2, 4, 6, and 15 months of age in the control group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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 Antibodies to Hepatitis B Surface Antigen	Participant serum samples were collected for testing with an enhanced chemiluminescence assay for antibodies to Hepatitis B Surface Antigen. The unit of measure is milli International Units/mL (mIU/mL).	Postdose 3 (Month 7)
Geometric Mean Concentration of Antibodies to Diphtheria Toxin	Participant serum samples were collected for testing with a Micrometabolic Inhibition Test for neutralizing antibodies to diphtheria toxin. The unit of measure is International Units/mL (IU/mL).	Postdose 3 (Month 7)
Geometric Mean Concentration of Antibodies to Tetanus Toxin	Participant serum samples were collected for testing with an Enzyme-linked Immunosorbent Assay (ELISA) for anti-tetanus antibodies.	Postdose 3 (Month 7)
Geometric Mean Titer for Antibodies to Poliovirus Type 1	Participant serum samples were collected for testing with a Micrometabolic Inhibition Test for neutralizing antibodies to Poliovirus Type 1. The unit of measure is titer (reciprocal of highest dilution with neutralizing activity).	Postdose 3 (Month 7)
Geometric Mean Titer for Antibodies to Poliovirus Type 2	Participant serum samples were collected for testing with a Micrometabolic Inhibition Test for neutralizing antibodies to Poliovirus Type 2.	Postdose 3 (Month 7)
Geometric Mean Titer for Antibodies to Poliovirus Type 3	Participant serum samples were collected for testing with a Micrometabolic Inhibition Test for neutralizing antibodies to Poliovirus Type 3.	Postdose 3 (Month 7)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 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)
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 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 a 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 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 IU/mL.	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 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. Analysis for this outcome included only non-inferiority of V419 Lots A, B, and C Combined versus Control.	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. Analysis for this outcome included only non-inferiority of V419 Lots A, B, and C Combined versus Control.	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. Analysis for this outcome included only non-inferiority of V419 Lots A, B, and C Combined versus Control.	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. Analysis for this outcome included only non-inferiority of V419 Lots A, B, and C Combined versus Control.	Postdose 4 (Month 16)
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 <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. Analysis for this outcome included only non-inferiority of V419 Lots A, B, and C Combined versus Control.	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 <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. Analysis for this outcome included only non-inferiority of V419 Lots A, B, and C Combined versus Control.	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 <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. Analysis for this outcome included only non-inferiority of V419 Lots A, B, and C Combined versus Control.	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 <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. Analysis for this outcome included only non-inferiority of V419 Lots A, B, and C Combined versus Control.	Postdose 4 (Month 16)
Geometric Mean Concentration of Antibodies to Pneumococcal Serotypes	Participant serum samples were collected for testing with a multiplex electrochemiluminescence-based detection assay for serotype-specific pneumococcal polysaccharide antibodies. Analysis for this outcome included only non-inferiority of V419 Lots A, B, and C Combined versus Control.	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: Fever, Vomiting, Crying abnormal, Drowsiness, Appetite lost, 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: Fever (Pyrexia), >=39.5°C rectal; Vomiting, >=6 episodes per 24 hours or requiring parenteral hydration; Crying abnormal, >3 hours; Drowsiness (Somnolence), Sleeping most of the time or difficult to wake up; Appetite lost, Refuses >=3 feeds or refuses most feeds; Irritability, Inconsolable.	Up to 5 days after any infant vaccination (up to 6 months)

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Block SL, Klein NP, Sarpong K, Russell S, Fling J, Petrecz M, Flores S, Xu J, Liu G, Stek JE, Foglia G, Lee AW. Lot-to-lot Consistency, Safety, Tolerability and Immunogenicity of an Investigational Hexavalent Vaccine in US Infants. Pediatr Infect Dis J. 2017 Feb;36(2):202-208. doi: 10.1097/INF.0000000000001405.

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2011
• Primary Completion (Actual): December 18, 2012
• Study Completion (Actual): July 26, 2013

Study Registration Dates

• First Submitted: April 21, 2011
• First Submitted That Met QC Criteria: April 22, 2011
• First Posted (Estimate): April 25, 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: V419-006

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