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

This study has been completed.
Sponsor:
Collaborator:
Sanofi Pasteur MSD
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01337167
First received: April 15, 2011
Last updated: February 18, 2016
Last verified: February 2016
  Purpose
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.

Condition Intervention Phase
Bacterial Infections
Virus Diseases
Biological: V419
Biological: DAPTACEL™
Biological: PedvaxHIB™
Biological: Prevnar 13™
Biological: RotaTeq™
Biological: PENTACEL™
Biological: Recombivax HB vaccine
Biological: ActHIB™
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: 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™

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Percentage of Participants Responding to Polyribosylribitol Phosphate Antigen [ Time Frame: Postdose 3 (Month 7) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Responding to Hepatitis B Surface Antigen [ Time Frame: Postdose 3 (Month 7) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Responding to Diphtheria Toxin [ Time Frame: Postdose 3 (Month 7) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Responding to Tetanus Toxin [ Time Frame: Postdose 3 (Month 7) ] [ Designated as safety issue: No ]
    Participant serum samples were collected for testing with an ELISA for anti-tetanus antibodies. Response was defined as a titer >=0.1 IU/mL.

  • Percentage of Participants Responding to Pertussis Toxin [ Time Frame: Postdose 3 (Month 7) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Responding to Pertussis Filamentous Hemagglutinin [ Time Frame: Postdose 3 (Month 7) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Responding to Pertussis Pertactin [ Time Frame: Postdose 3 (Month 7) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Responding to Pertussis Fimbriae [ Time Frame: Postdose 3 (Month 7) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Responding to Poliovirus Type 1 [ Time Frame: Postdose 3 (Month 7) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Responding to Poliovirus Type 2 [ Time Frame: Postdose 3 (Month 7) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Responding to Poliovirus Type 3 [ Time Frame: Postdose 3 (Month 7) ] [ Designated as safety issue: No ]
    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.

  • Geometric Mean Concentration of Antibodies to Pertussis Toxin [ Time Frame: Postdose 3 (Month 7) ] [ Designated as safety issue: No ]
    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).

  • Geometric Mean Concentration of Antibodies to Pertussis Filamentous Hemagglutinin [ Time Frame: Postdose 3 (Month 7) ] [ Designated as safety issue: No ]
    Participant serum samples were collected for testing with an ELISA for antibodies to pertussis filamentous hemagglutinin.

  • Geometric Mean Concentration of Antibodies to Pertussis Pertactin [ Time Frame: Postdose 3 (Month 7) ] [ Designated as safety issue: No ]
    Participant serum samples were collected for testing with an ELISA for antibodies to pertussis pertactin.

  • Geometric Mean Concentration of Antibodies to Pertussis Fimbriae [ Time Frame: Postdose 3 (Month 7) ] [ Designated as safety issue: No ]
    Participant serum samples were collected for testing with an ELISA for antibodies to pertussis fimbriae.

  • Percentage of Participants Responding to Pertussis Toxin [ Time Frame: Postdose 4 (Month 16) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Responding to Pertussis Filamentous Hemagglutinin [ Time Frame: Postdose 4 (Month 16) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Responding to Pertussis Pertactin [ Time Frame: Postdose 4 (Month 16) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Responding to Pertussis Fimbriae [ Time Frame: Postdose 4 (Month 16) ] [ Designated as safety issue: No ]
    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.

  • Geometric Mean Concentration of Antibodies to Pertussis Toxin [ Time Frame: Postdose 4 (Month 16) ] [ Designated as safety issue: No ]
    Participant serum samples were collected for testing with an ELISA for antibodies to pertussis toxin.

  • Geometric Mean Concentration of Antibodies to Pertussis Filamentous Hemagglutinin [ Time Frame: Postdose 4 (Month 16) ] [ Designated as safety issue: No ]
    Participant serum samples were collected for testing with an ELISA for antibodies to pertussis filamentous hemagglutinin.

  • Geometric Mean Concentration of Antibodies to Pertussis Pertactin [ Time Frame: Postdose 4 (Month 16) ] [ Designated as safety issue: No ]
    Participant serum samples were collected for testing with an ELISA for antibodies to pertussis pertactin.

  • Geometric Mean Concentration of Antibodies to Pertussis Fimbriae [ Time Frame: Postdose 4 (Month 16) ] [ Designated as safety issue: No ]
    Participant serum samples were collected for testing with an ELISA for antibodies to pertussis fimbriae.


Secondary Outcome Measures:
  • Geometric Mean Concentration of Antibodies to Polyribosylribitol Phosphate Antigen [ Time Frame: Postdose 3 (Month 7) ] [ Designated as safety issue: No ]
    Participant serum samples were collected for testing with a radioimmunoassay for antibodies to Haemophilus influenza type b capsular polysaccharide polyribosylribitol phosphate.

  • Geometric Mean Concentration of Immunoglobulin A (IgA) Antibodies to Rotavirus [ Time Frame: Postdose 3 (Month 7) ] [ Designated as safety issue: No ]
    Participant serum samples were collected for testing with an Enzyme-linked Immunosorbent assay for IgA antibodies to rotavirus.

  • Percentage of Participants Reporting Solicited Injection-site or Systemic Reactions [ Time Frame: Up to 5 days after any infant vaccination (up to 6 months) ] [ Designated as safety issue: Yes ]
    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.

  • Percentage of Participants Reporting One or More Solicited Adverse Events Related to Study Drug [ Time Frame: Up to 5 days after any infant vaccination (up to 6 months) ] [ Designated as safety issue: Yes ]
    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.

  • Percentage of Participants Reporting One or More Solicited Adverse Events Related to Study Drug [ Time Frame: Up to 5 days after each infant vaccination (up to 6 months) ] [ Designated as safety issue: Yes ]
    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.

  • Percentage of Participants With Elevated Temperature by Severity [ Time Frame: Up to 5 days after any infant vaccination (up to 6 months) ] [ Designated as safety issue: Yes ]
    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.

  • Percentage of Participants With Pyrexia, Febrile Convulsion, or Convulsion [ Time Frame: Up to 15 days after any infant vaccination (up to 6 months) ] [ Designated as safety issue: Yes ]
    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.

  • Percentage of Participants With Pyrexia, Febrile Convulsion, or Convulsion [ Time Frame: Up to 181 days after any infant vaccination (up to 12 months) ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 1473
Study Start Date: April 2011
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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

  Eligibility

Ages Eligible for Study:   46 Days to 89 Days   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01337167

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Sanofi Pasteur MSD
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Publications:
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01337167     History of Changes
Other Study ID Numbers: V419-005 
Study First Received: April 15, 2011
Results First Received: February 18, 2016
Last Updated: February 18, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Merck Sharp & Dohme Corp.:
Diphtheria
Tetanus
Whooping Cough (pertussis)
Poliomyelitis
Hepatitis B infection
Haemophilus influenzae type b infection

Additional relevant MeSH terms:
Infection
Bacterial Infections
Virus Diseases
Vaccines
Heptavalent Pneumococcal Conjugate Vaccine
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 29, 2016