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

NCT01337167 | Completed Phase 3 Results

• 1 other identifier: V419-005
• Study Type: interventional
• Target: 1,473
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Bacterial Infections; Virus Diseases

Keywords

Diphtheria; Tetanus; Whooping Cough (pertussis); Poliomyelitis; Hepatitis B infection; Haemophilus influenzae type b infection

Outcome Measures

Primary Outcomes (23)

• 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 Outcomes (8)

• Geometric Mean Concentration of Antibodies to Polyribosylribitol Phosphate Antigen

  Postdose 3 (Month 7)

• Geometric Mean Concentration of Immunoglobulin A (IgA) Antibodies to Rotavirus

  Postdose 3 (Month 7)

• Percentage of Participants Reporting Solicited Injection-site or Systemic Reactions

  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

  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

  Up to 5 days after each infant vaccination (up to 6 months)

Study Arms (2)

V419

EXPERIMENTAL

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; Biological: DAPTACEL™; Biological: PedvaxHIB™; Biological: Prevnar 13™; Biological: RotaTeq™

Control

ACTIVE COMPARATOR

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™; Biological: Prevnar 13™; Biological: RotaTeq™; Biological: PENTACEL™; Biological: Recombivax HB vaccine; Biological: ActHIB™

Interventions

V419 BIOLOGICAL

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

V419

DAPTACEL™ BIOLOGICAL

DAPTACEL™ 0.5 mL intramuscular injection at 15 months of age

Control; V419

PedvaxHIB™ BIOLOGICAL

PedvaxHIB™ 0.5 mL intramuscular injection at 15 months of age

V419

Prevnar 13™ BIOLOGICAL

Prevnar 13™ 0.5 mL intramuscular injection at 2, 4, 6, and 15 months of age

Control; V419

RotaTeq™ BIOLOGICAL

RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age

Also known as: V260

Control; V419

PENTACEL™ BIOLOGICAL

PENTACEL™ 0.5 mL intramuscular injection at 2, 4, and 6 months of age

Control

Recombivax HB vaccine BIOLOGICAL

Recombivax HB vaccine 0.5 mL intramuscular injection at 2 and 6 months of age

Control

ActHIB™ BIOLOGICAL

ActHIB™ 0.5 mL intramuscular injection at 15 months of age

Control

Eligibility Criteria

• Age: 46 Days - 89 Days
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead
• MCM Vaccines B.V.: collaborator

Related Publications (1)

• 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.

  PMID: 26216331 BACKGROUND

MeSH Terms

Conditions

Bacterial Infections; Virus Diseases; Diphtheria; Tetanus; Whooping Cough; Poliomyelitis; Hepatitis B; Haemophilus Infections

Interventions

Diphtheria-Tetanus-acellular Pertussis Vaccines; Haemophilus influenzae-type b polysaccharide-Neisseria meningitidis outer membrane protein conjugate vaccine; 13-valent pneumococcal vaccine; RotaTeq; Rotavirus Vaccines; pentacel; Haemophilus influenza type b polysaccharide vaccine-tetanus toxin conjugate

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections; Corynebacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Clostridium Infections; Bordetella Infections; Gram-Negative Bacterial Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Myelitis; Central Nervous System Infections; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Neuroinflammatory Diseases; Neuromuscular Diseases; Blood-Borne Infections; Communicable Diseases; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases; Pasteurellaceae Infections

Intervention Hierarchy (Ancestors)

Pertussis Vaccine; Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures; Diphtheria Toxoid; Toxoids; Tetanus Toxoid; Vaccines, Combined; Vaccines, Acellular; Vaccines, Subunit; Viral Vaccines

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• 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: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2011
• First Posted: April 18, 2011
• Study Start: April 19, 2011
• Primary Completion: May 9, 2013
• Study Completion: May 9, 2013
• Last Updated: November 15, 2018
• Results First Posted: March 16, 2016

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will share