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Safety, Tolerability, and Immunogenicity of V419 in Healthy Infants When Given at 2, 3, 4 and 12 Months (V419-007)

Primary Purpose

Bacterial Infections, Virus Diseases

Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
V419
INFANRIX™ hexa
RotaTeq
Prevenar 13
ProQuad™
Sponsored by
MCM Vaccines B.V.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Bacterial Infections focused on measuring combination vaccine, diphtheria, pertussis, tetanus, hepatitis B, Hep B, Haemophilus influenzae b, Hib, polio, poliovirus

Eligibility Criteria

46 Days - 74 Days (Child)All SexesAccepts Healthy Volunteers

Inclusion Criteria

  • Healthy infants able to attend all study visits
  • Parent(s)/legal representative able to read, understand, and complete study questionnaires

Exclusion Criteria

  • History of congenital or acquired immunodeficiency
  • Received or is expected to receive immunosuppressive agents or systemic immunomodulatory steroids
  • History of leukemia, lymphoma, malignant melanoma, or myeloproliferative disorder
  • Hypersensitivity to any of the vaccine components or history of a life-threatening reaction to a vaccine containing the same substances as the study vaccines or concomitant study vaccines
  • Has any chronic illness that could interfere with study conduct or completion
  • Received any immune globulin, blood, or blood-derived products since birth
  • Received a dose of hepatitis B vaccine prior to the study
  • 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 thereof
  • Fever within 24 hours prior to enrollment
  • Received any non-study vaccine within 30 days prior to enrollment, except for inactivated influenza vaccine, which is permitted 14 days or more prior to enrollment
  • Has a coagulation disorder
  • Has developmental delay or neurological disorder
  • Participant or his/her mother has a medical history of hepatitis B surface antigen (HBsAg) seropositivity
  • History of measles, mumps, rubella, varicella, Haemophilus influenzae type B, hepatitis B, diphtheria, tetanus, pertussis, rotavirus, invasive pneumococcal, or poliomyelitis infection

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    PR5I

    INFANRIX™ hexa

    Arm Description

    V419 + RotaTeq + Prevenar 13 + ProQuad

    INFANRIX™ hexa + RotaTeq + Prevenar 13 + ProQuad

    Outcomes

    Primary Outcome Measures

    Percentage of Participants Vaccinated With PR5I With Acceptable Antibody (Ab) Response to Haemophilus Influenzae Type b, Diphtheria, Tetanus, and Poliovirus Types 1, 2 & 3, at 5 Months
    Antibody titres in the PR5I group were measured by Radioimmunoassay (RIA) for Haemophilus influenzae type b (PRP), Micrometabolic inhibition test (MIT) for diphtheria & poliovirus, and Enzyme-Linked Immunosorbent Assay (ELISA) for tetanus. Percentage of participants with an Ab titre ≥0.15 μg/mL for Haemophilus influenzae type b (Hib) (polyribosylribitol phosphate, PRP); ≥0.01 IU/mL; for diphtheria & tetanus; ≥8 (1/dil) for inactivated poliovirus types 1, 2 & 3 (IPV1, 2 & 3) are reported. 95% confidence interval (CI) were calculated based on the exact binomial method by Clopper and Pearson. The immune response to PR5I vaccine was considered as acceptable if the lower bounds of the 2-sided 95% CI for the response rates were greater than the predetermined lower CI limits for PRP, diphtheria (80%), tetanus (90%), and IPV1, 2 & 3 (90%).
    Percentage of Participants Vaccinated With PR5I With Acceptable Ab Response or Seroresponse Rates to All Antigens Contained in the PR5I Vaccine One Month After the Toddler Dose at 13 Months
    Antibody titres in the PR5I group were measured by RIA for PRP, MIT for diphtheria & poliovirus, enhanced Chemiluminescence assay (ECi)) for Hepatitis B surface antigen (HBsAg) and ELISA for tetanus, Pertussis toxoid (PT), Filamentous haemagglutinin (FHA), Fimbriae types 2 & 3 (FIM) & Pertactin (PRN). Percentage of participants with an Ab titre ≥1.0 μg/mL for Hib (PRP); ≥0.1 IU/mL; for diphtheria & tetanus; ≥10 mIU/mL HBsAg; ≥8 (1/dil) for IPV1, 2 & 3, and seroresponse to PT, FHA, FIM and PRN are reported. 95% confidence interval (CI) were calculated based on the exact binomial method by Clopper and Pearson. The immune response to PR5I vaccine was considered as acceptable if the lower bounds of the 2-sided 95% CI for the response rates were greater than the lower CI limits for PRP, PT, FHA, FIM, and PRN (75%); Diphtheria (80%); HBsAG, IPV 1, 2, 3 (90%).
    Percentage of Participants Vaccinated With PR5I Compared With INFANRIX™ Hexa With Acceptable Ab Response to Haemophilus Influenzae Type b, Diphtheria, Tetanus, and Poliovirus Types 1, 2 & 3, at 5 Months
    Antibody titres were measured by RIA for PRP, MIT for diphtheria & poliovirus, and ELISA for tetanus. Percentage of participants with an Ab titre ≥0.15 μg/mL for Hib) (PRP); ≥0.01 IU/mL; for diphtheria & tetanus; ≥8 (1/dil) for inactivated poliovirus types 1, 2 & 3 (IPV1, 2 & 3) are reported. The estimated response rates are based on the method by Miettinen and Nurminen stratified by country.
    Percentage of Participants Vaccinated With PR5I Compared With INFANRIX™ Hexa With Acceptable Ab Response Rates to Hepatitis B and Seroresponse to Pertussis Antigens Pt, FHA and PRN One Month After the Toddler Dose at 13 Months Old
    Antibody titres were measured by ECi for HBsAg and ELISA for PT, FHA, & PRN. Percentage of participants with an Ab titre ≥10 mIU/mL HBsAg; ≥8 (1/dil) for IPV1, 2 & 3, and seroresponse to PT, FHA, and PRN are reported. The estimated response rates are based on the method by Miettinen and Nurminen stratified by country.

    Secondary Outcome Measures

    Percentage of Participants Vaccinated With PR5I With Acceptable Ab Response to Measles, Mumps, Rubella and Varicella One Month After the Toddler Dose of ProQuad at 13 Months Old
    Ab titres were measured by ELISA, excepting the Ab to varicella which was determined by glycoprotein ELISA. Percentage of participants with an Ab titre ≥255 mIU/mL for measles, ≥10 Ab units/mL for mumps, ≥10 IU/mL for rubella, and ≥5 gpELISA units/mL for varicella are reported. 95% CI were calculated based on the exact binomial method by Clopper and Pearson. The immune response to ProQuad vaccine was considered as acceptable if the lower bounds of the 2-sided 95% CI for the response rates were greater than the predetermined lower CI limits: 90% for measles, mumps & rubella, and 76% for varicella.
    Percentage of Participants Vaccinated With PR5I Compared With INFANRIX™ Hexa With Acceptable Ab Response to Measles, Mumps, Rubella and Varicella One Month After the Toddler Dose of ProQuad at 13 Months Old
    Ab titres were measured by ELISA, excepting the Ab to varicella which was determined by glycoprotein ELISA. Percentage of participants with an Ab titre ≥255 mIU/mL for measles, ≥10 Ab units/mL for mumps, ≥10 IU/mL for rubella, and ≥5 gpELISA units/mL for varicella are reported. The estimated response rates are based on the method by Miettinen and Nurminen stratified by country.
    Percentage of Participants With Injection-site and Systemic Adverse Events (AEs) From Day 1 to Day 15 After Any Vaccination
    Global safety was assessed by measuring injection-site and systemic AEs reported daily on the Vaccination Report Card (VRC) by the parent(s) or legal representative from Day 1 to Day 15 (D1-D15) after each hexavalent vaccination. Solicited injection-site and systemic AEs were reported daily from Day 1 to Day 5 (D1-D5) after each hexavalent vaccination. AEs at injection sites were always considered as vaccine-related (Injection-Site Reactions (ISRs)). The investigator assessed whether systemic AEs were related (V-related) or not to the vaccine. All AEs (related and unrelated) are reported.
    Percentage of Participants Reporting Solicited ISRs From Day 1 to Day 5 After Any Vaccination
    Solicited ISRs were defined as injection-site erythema, injection-site pain, and injection-site swelling occurring from Day 1 (D1) to Day 5 (D5) after vaccination. AEs at injection sites were always considered as vaccine-related (Injection-Site Reactions (ISRs)).
    Percentage of Participants Reporting Unsolicited ISRs From Day 1 to Day 15 After Any Vaccination
    Unsolicited ISRs with incidence ≥1% after any vaccination were reported daily on the VRC by the parent(s) or legal representative from (D1-D15). AEs at injection sites were always considered as vaccine-related ISRs
    Percentage of Participants Reporting Solicited Systemic AE From Day 1 to Day 5 After Any Vaccination
    Solicited systemic AEs were defined as crying, decreased appetite, irritability, pyrexia (rectal temperature ≥38.0°C), somnolence, and vomiting occurring from D1 to D5 after vaccination. The investigator assessed whether these systemic AEs were related or not to the vaccines. All (related and unrelated) AEs are reported.

    Full Information

    First Posted
    April 22, 2011
    Last Updated
    April 29, 2019
    Sponsor
    MCM Vaccines B.V.
    Collaborators
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01341639
    Brief Title
    Safety, Tolerability, and Immunogenicity of V419 in Healthy Infants When Given at 2, 3, 4 and 12 Months (V419-007)
    Official Title
    A Phase III Randomized, Double-Blind, Active-Comparator Controlled Clinical Trial to Study the Safety, Tolerability, and Immunogenicity of V419 in Healthy Infants When Given at 2, 3, 4, and 12 Months (V419-007-03)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    April 2019
    Overall Recruitment Status
    Completed
    Study Start Date
    May 26, 2011 (Actual)
    Primary Completion Date
    March 13, 2013 (Actual)
    Study Completion Date
    March 13, 2013 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    MCM Vaccines B.V.
    Collaborators
    Merck Sharp & Dohme LLC

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    This study will determine whether participants who receive the vaccine V419 at 2, 3, 4, and 12 months of age have an acceptable immune response to the vaccine. The study will also determine whether the immune response to V419 is similar to that of participants who receive a licensed vaccine control.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Bacterial Infections, Virus Diseases
    Keywords
    combination vaccine, diphtheria, pertussis, tetanus, hepatitis B, Hep B, Haemophilus influenzae b, Hib, polio, poliovirus

    7. Study Design

    Primary Purpose
    Prevention
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    1250 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    PR5I
    Arm Type
    Experimental
    Arm Description
    V419 + RotaTeq + Prevenar 13 + ProQuad
    Arm Title
    INFANRIX™ hexa
    Arm Type
    Active Comparator
    Arm Description
    INFANRIX™ hexa + RotaTeq + Prevenar 13 + ProQuad
    Intervention Type
    Biological
    Intervention Name(s)
    V419
    Intervention Description
    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, 3, 4, and 12 months of age.
    Intervention Type
    Biological
    Intervention Name(s)
    INFANRIX™ hexa
    Intervention Description
    INFANRIX™ hexa 0.5 mL intramuscular injection at 2, 3, 4, and 12 months of age.
    Intervention Type
    Biological
    Intervention Name(s)
    RotaTeq
    Intervention Description
    RotaTeq (pentavalent combination live vaccine of 5 human-bovine reassortant rotavirus strains) 2 mL oral dose at 2, 3, and 4 months of age
    Intervention Type
    Biological
    Intervention Name(s)
    Prevenar 13
    Intervention Description
    Prevenar 13 0.5 mL intramuscular injection at 2, 3, 4,and 13 months of age
    Intervention Type
    Biological
    Intervention Name(s)
    ProQuad™
    Intervention Description
    ProQuad™ 0.5 mL subcutaneous injection at 12 and 13 months of age
    Primary Outcome Measure Information:
    Title
    Percentage of Participants Vaccinated With PR5I With Acceptable Antibody (Ab) Response to Haemophilus Influenzae Type b, Diphtheria, Tetanus, and Poliovirus Types 1, 2 & 3, at 5 Months
    Description
    Antibody titres in the PR5I group were measured by Radioimmunoassay (RIA) for Haemophilus influenzae type b (PRP), Micrometabolic inhibition test (MIT) for diphtheria & poliovirus, and Enzyme-Linked Immunosorbent Assay (ELISA) for tetanus. Percentage of participants with an Ab titre ≥0.15 μg/mL for Haemophilus influenzae type b (Hib) (polyribosylribitol phosphate, PRP); ≥0.01 IU/mL; for diphtheria & tetanus; ≥8 (1/dil) for inactivated poliovirus types 1, 2 & 3 (IPV1, 2 & 3) are reported. 95% confidence interval (CI) were calculated based on the exact binomial method by Clopper and Pearson. The immune response to PR5I vaccine was considered as acceptable if the lower bounds of the 2-sided 95% CI for the response rates were greater than the predetermined lower CI limits for PRP, diphtheria (80%), tetanus (90%), and IPV1, 2 & 3 (90%).
    Time Frame
    One month after post-dose 3 of PRI5 (5 months old)
    Title
    Percentage of Participants Vaccinated With PR5I With Acceptable Ab Response or Seroresponse Rates to All Antigens Contained in the PR5I Vaccine One Month After the Toddler Dose at 13 Months
    Description
    Antibody titres in the PR5I group were measured by RIA for PRP, MIT for diphtheria & poliovirus, enhanced Chemiluminescence assay (ECi)) for Hepatitis B surface antigen (HBsAg) and ELISA for tetanus, Pertussis toxoid (PT), Filamentous haemagglutinin (FHA), Fimbriae types 2 & 3 (FIM) & Pertactin (PRN). Percentage of participants with an Ab titre ≥1.0 μg/mL for Hib (PRP); ≥0.1 IU/mL; for diphtheria & tetanus; ≥10 mIU/mL HBsAg; ≥8 (1/dil) for IPV1, 2 & 3, and seroresponse to PT, FHA, FIM and PRN are reported. 95% confidence interval (CI) were calculated based on the exact binomial method by Clopper and Pearson. The immune response to PR5I vaccine was considered as acceptable if the lower bounds of the 2-sided 95% CI for the response rates were greater than the lower CI limits for PRP, PT, FHA, FIM, and PRN (75%); Diphtheria (80%); HBsAG, IPV 1, 2, 3 (90%).
    Time Frame
    One month after Toddler dose of PRI5 (13 months old)
    Title
    Percentage of Participants Vaccinated With PR5I Compared With INFANRIX™ Hexa With Acceptable Ab Response to Haemophilus Influenzae Type b, Diphtheria, Tetanus, and Poliovirus Types 1, 2 & 3, at 5 Months
    Description
    Antibody titres were measured by RIA for PRP, MIT for diphtheria & poliovirus, and ELISA for tetanus. Percentage of participants with an Ab titre ≥0.15 μg/mL for Hib) (PRP); ≥0.01 IU/mL; for diphtheria & tetanus; ≥8 (1/dil) for inactivated poliovirus types 1, 2 & 3 (IPV1, 2 & 3) are reported. The estimated response rates are based on the method by Miettinen and Nurminen stratified by country.
    Time Frame
    One month after post-dose 3 of PRI5 (5 months old)
    Title
    Percentage of Participants Vaccinated With PR5I Compared With INFANRIX™ Hexa With Acceptable Ab Response Rates to Hepatitis B and Seroresponse to Pertussis Antigens Pt, FHA and PRN One Month After the Toddler Dose at 13 Months Old
    Description
    Antibody titres were measured by ECi for HBsAg and ELISA for PT, FHA, & PRN. Percentage of participants with an Ab titre ≥10 mIU/mL HBsAg; ≥8 (1/dil) for IPV1, 2 & 3, and seroresponse to PT, FHA, and PRN are reported. The estimated response rates are based on the method by Miettinen and Nurminen stratified by country.
    Time Frame
    One month after Toddler dose of PRI5 (13 months old)
    Secondary Outcome Measure Information:
    Title
    Percentage of Participants Vaccinated With PR5I With Acceptable Ab Response to Measles, Mumps, Rubella and Varicella One Month After the Toddler Dose of ProQuad at 13 Months Old
    Description
    Ab titres were measured by ELISA, excepting the Ab to varicella which was determined by glycoprotein ELISA. Percentage of participants with an Ab titre ≥255 mIU/mL for measles, ≥10 Ab units/mL for mumps, ≥10 IU/mL for rubella, and ≥5 gpELISA units/mL for varicella are reported. 95% CI were calculated based on the exact binomial method by Clopper and Pearson. The immune response to ProQuad vaccine was considered as acceptable if the lower bounds of the 2-sided 95% CI for the response rates were greater than the predetermined lower CI limits: 90% for measles, mumps & rubella, and 76% for varicella.
    Time Frame
    One month after Toddler dose of PRI5 (13 months old)
    Title
    Percentage of Participants Vaccinated With PR5I Compared With INFANRIX™ Hexa With Acceptable Ab Response to Measles, Mumps, Rubella and Varicella One Month After the Toddler Dose of ProQuad at 13 Months Old
    Description
    Ab titres were measured by ELISA, excepting the Ab to varicella which was determined by glycoprotein ELISA. Percentage of participants with an Ab titre ≥255 mIU/mL for measles, ≥10 Ab units/mL for mumps, ≥10 IU/mL for rubella, and ≥5 gpELISA units/mL for varicella are reported. The estimated response rates are based on the method by Miettinen and Nurminen stratified by country.
    Time Frame
    One month after Toddler dose of PRI5 (13 months old)
    Title
    Percentage of Participants With Injection-site and Systemic Adverse Events (AEs) From Day 1 to Day 15 After Any Vaccination
    Description
    Global safety was assessed by measuring injection-site and systemic AEs reported daily on the Vaccination Report Card (VRC) by the parent(s) or legal representative from Day 1 to Day 15 (D1-D15) after each hexavalent vaccination. Solicited injection-site and systemic AEs were reported daily from Day 1 to Day 5 (D1-D5) after each hexavalent vaccination. AEs at injection sites were always considered as vaccine-related (Injection-Site Reactions (ISRs)). The investigator assessed whether systemic AEs were related (V-related) or not to the vaccine. All AEs (related and unrelated) are reported.
    Time Frame
    Day 1 to Day 15 after any vaccination
    Title
    Percentage of Participants Reporting Solicited ISRs From Day 1 to Day 5 After Any Vaccination
    Description
    Solicited ISRs were defined as injection-site erythema, injection-site pain, and injection-site swelling occurring from Day 1 (D1) to Day 5 (D5) after vaccination. AEs at injection sites were always considered as vaccine-related (Injection-Site Reactions (ISRs)).
    Time Frame
    Day 1 to Day 5 after any vaccination
    Title
    Percentage of Participants Reporting Unsolicited ISRs From Day 1 to Day 15 After Any Vaccination
    Description
    Unsolicited ISRs with incidence ≥1% after any vaccination were reported daily on the VRC by the parent(s) or legal representative from (D1-D15). AEs at injection sites were always considered as vaccine-related ISRs
    Time Frame
    Day 1 to Day 15 after any vaccination
    Title
    Percentage of Participants Reporting Solicited Systemic AE From Day 1 to Day 5 After Any Vaccination
    Description
    Solicited systemic AEs were defined as crying, decreased appetite, irritability, pyrexia (rectal temperature ≥38.0°C), somnolence, and vomiting occurring from D1 to D5 after vaccination. The investigator assessed whether these systemic AEs were related or not to the vaccines. All (related and unrelated) AEs are reported.
    Time Frame
    Day 1 to Day 5 after any vaccination

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    46 Days
    Maximum Age & Unit of Time
    74 Days
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    Inclusion Criteria Healthy infants able to attend all study visits Parent(s)/legal representative able to read, understand, and complete study questionnaires Exclusion Criteria History of congenital or acquired immunodeficiency Received or is expected to receive immunosuppressive agents or systemic immunomodulatory steroids History of leukemia, lymphoma, malignant melanoma, or myeloproliferative disorder Hypersensitivity to any of the vaccine components or history of a life-threatening reaction to a vaccine containing the same substances as the study vaccines or concomitant study vaccines Has any chronic illness that could interfere with study conduct or completion Received any immune globulin, blood, or blood-derived products since birth Received a dose of hepatitis B vaccine prior to the study 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 thereof Fever within 24 hours prior to enrollment Received any non-study vaccine within 30 days prior to enrollment, except for inactivated influenza vaccine, which is permitted 14 days or more prior to enrollment Has a coagulation disorder Has developmental delay or neurological disorder Participant or his/her mother has a medical history of hepatitis B surface antigen (HBsAg) seropositivity History of measles, mumps, rubella, varicella, Haemophilus influenzae type B, hepatitis B, diphtheria, tetanus, pertussis, rotavirus, invasive pneumococcal, or poliomyelitis infection
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Medical Director
    Organizational Affiliation
    Merck Sharp & Dohme LLC
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
    IPD Sharing URL
    http://engagezone.msd.com/ds_documentation.php
    Citations:
    PubMed Identifier
    27846055
    Citation
    Vesikari T, Becker T, Vertruyen AF, Poschet K, Flores SA, Pagnoni MF, Xu J, Liu GF, Stek JE, Boisnard F, Thomas S, Ziani E, Lee AW. A Phase III Randomized, Double-blind, Clinical Trial of an Investigational Hexavalent Vaccine Given at Two, Three, Four and Twelve Months. Pediatr Infect Dis J. 2017 Feb;36(2):209-215. doi: 10.1097/INF.0000000000001406.
    Results Reference
    derived

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    Safety, Tolerability, and Immunogenicity of V419 in Healthy Infants When Given at 2, 3, 4 and 12 Months (V419-007)

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