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Immunogenicity and Safety of Sanofi Pasteur's Combined Vaccine Given as a Three-Dose Primary Series at 2, 3,4 Months of Age and Followed by a Booster Dose Given at 16 to 17 Months of Age in Vietnamese Infants Who Previously Received a Dose of Hepatitis B Vaccine at Birth or Within 1 Week After Birth

Primary Purpose

Diphtheria, Tetanus, Pertussis

Status
Completed
Phase
Phase 3
Locations
Vietnam
Study Type
Interventional
Intervention
Hexaxim®
Sponsored by
Sanofi Pasteur, a Sanofi Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Diphtheria focused on measuring Diphtheria, Tetanus, Pertussis, Poliomyelitis, Hepatitis B, Haemophilus Influenzae Type b, DTaP-IPV-Hep B-PRP-T Combined Vaccine (Hexaxim®)

Eligibility Criteria

61 Days - 91 Days (Child)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Aged 61 to 91 days on the day of the first study visit
  • Born at full term of pregnancy (≥ 37 weeks) and with a birth weight ≥2.5 kg
  • Informed consent form has been signed and dated by the parent(s) or other legally acceptable representative (and by an independent witness if required by local regulations)
  • Subject and parent/legally acceptable representative are able to attend all scheduled visits and to comply with all trial procedures
  • Have received one dose of Hep B vaccine at birth or within 1 week after birth (documented according to the national recommendations).

Exclusion Criteria:

  • Participation in the 4 weeks preceding the first trial vaccination or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure
  • Receipt of any vaccine in the 4 weeks preceding the first trial vaccination or planned receipt of any other vaccine within the period from 8 days before to 8 days after each subsequent trial vaccination except for Bacille Calmette Guerin (BCG) vaccination (any administration of oral poliovirus vaccine (OPV) in the context of oral poliovirus vaccine-national immunization days (NIDs) does not fall within the scope of this exclusion criterion)
  • Previous vaccination against diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B (except the dose of Hep B vaccine given at birth or within 1 week after birth) diseases or Haemophilus influenzae type b infection with either the trial vaccine or another vaccine (any administration of OPV in the context of OPV-NIDs does not fall within the scope of this exclusion criterion)
  • Past or current receipt of immune globulins, blood or blood-derived products or planned administration during the trial
  • Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy since birth; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks since birth)
  • History of diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, or Haemophilus influenzae type b infections (confirmed either clinically, serologically or microbiologically)
  • Known personal or maternal history of Human Immunodeficiency Virus (HIV), or hepatitis C seropositivity
  • Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine used in the trial or to a vaccine containing any of the same substances
  • Known thrombocytopenia, as reported by the parent/legally acceptable representative
  • Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination
  • History of seizures
  • In an emergency setting, or hospitalized involuntarily
  • Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion
  • Moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination or febrile illness (temperature ≥38.0°C). A prospective subject should not be included in the study until the condition has resolved or the febrile event has subsided
  • Identified as a natural or adopted child of the Investigator, relatives or employee with direct involvement in the proposed study.

Sites / Locations

  • Preventive Medicine Centre of Thai Binh Province

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

DTaP-IPV-HB-PRP~T Vaccine

Arm Description

All participants will receive 3 doses of 0.5 mL DTaP-IPV-HB-PRP~T combined vaccine, intramuscularly, at 2, 3 and 4 months of age (primary series), followed by a booster dose approximately 12 months after the completion of the primary series (at 16 to 17 months of age).

Outcomes

Primary Outcome Measures

Number of Participants Reporting Solicited Injection Site Reactions or Solicited Systemic Reactions
Solicited injection site reactions: tenderness, erythema, and swelling (and extensive limb swelling for booster dose). Solicited systemic reactions: fever, vomiting, crying abnormal, drowsiness, appetite loss, and irritability

Secondary Outcome Measures

Number of Subjects With Seroprotection/Seroconversion/Vaccine Response After Infant Series in Cohort 1
Seroconversion:4-fold increase in anti-Pertussis(PT)& anti-Filamentous hemagglutinin(FHA) antibody(Ab) concentrations from pre-vaccination to one month after first dose.Vaccine response:anti-PT/anti-FHA Ab concentrations in Enzyme Linked Immunosorbent Assay(ELISA) units(EU)/mL>=4*Lower Limit of Quantitation(LLOQ) if pre-vaccination concentration <4*LLOQ/>=pre-vaccination concentration if prevaccination concentrations>=4*LLOQ. Seroprotection:anti-Diphtheria &anti-Tetanus>=0.01 International Units(IU)/mL&>=0.1 IU/mL;anti-PT &anti-FHA>=2 EU/mL &>=8 EU/mL;anti-Polyribosyl Ribitol Phosphate(PRP)>=0.15 microgram per milliliter(mcg/mL) &>=1.0mcg/mL;anti-Polio types 1,2,&3>=8(1/dilution),anti-Hepatitis B>=10 mili-international units per mililiter(mIU/mL)&>=100 mIU/mL
Number of Subjects With Seroprotection/Seroconversion/Vaccine and Booster Response Before and After Booster Vaccination in Cohort 1
Seroconversion:4-fold increase in anti-PT & anti-FHA Ab concentrations from pre-booster vaccination to 1 month after booster dose.Vaccine response post-booster vaccination:post-booster Ab concentrations>=4*LLOQ if pre-dose 1 Ab concentrations<4*LLOQ/post-booster Ab concentrations>=predose 1 Ab concentrations if pre-dose 1>=4*LLOQ. Booster response:>=4 fold Ab concentrations increase from pre-dose 4 to one-month post-dose 4 if one-month post-dose 3<4*LLOQ/>=2 fold Ab concentrations increase from pre-dose 4 to one-month post-dose 4 if pre-dose 4>=4*LLOQ.Seroprotection:anti-Diphtheria & anti-Tetanus>=0.01 IU/mL &>=0.1 IU/mL &>=1.0 IU/mL;anti-PRP >=0.15 mcg/mL &>=1.0 mcg/mL;anti-Polio types 1, 2, & 3>=8 (1/dilution),anti-Hepatitis B>=10 mIU/mL &>=100 mIU/mL
Geometric Mean Titers or Geometric Mean Concentrations of DTaP-IPV-HB-PRP~T Antibodies Before and After Infant Series in Cohort
Geometric mean of concentrations of antibodies against PT, FHA, diphtheria, tetanus, PRP, poliovirus 1, 2 and 3, and Hep B
Geometric Mean Titers or Geometric Mean Concentrations of DTaP-IPV-HB-PRP~T Antibodies Before and After Booster Vaccination in Cohort 1
Geometric mean of concentrations of antibodies against PT, FHA, diphtheria, tetanus, PRP, poliovirus 1, 2 and 3, and Hep B
Percentage of Subjects With Seroprotection/Seroconversion Rates after Infant Series in Cohort 1 and Group 3 of A3L15 (NCT01105559)
Seroconversion defined as 4-fold increase in anti-PT & anti-FHA Ab concentrations from pre-vaccination to one month after first dose. Seroprotection defined as following: anti-Diphtheria & anti-Tetanus >=0.01 IU/mL; anti-PT & anti-FHA >=4EU/mL; anti-PRP >=0.15 mcg/mL; anti-Polio types 1, 2, & 3 >=8 (1/dilution), anti-Hepatitis B >=10 mIU/mL. Results observed in Group 3 of Study A3L15 (NCT00362336), a study conducted in South Africa where participants had been given DTaP-IPV-HB-PRP~T at 6, 10, and 14 weeks of age following Hep B vaccination at birth, were used as the non-inferiority reference value

Full Information

First Posted
April 23, 2015
Last Updated
March 24, 2022
Sponsor
Sanofi Pasteur, a Sanofi Company
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1. Study Identification

Unique Protocol Identification Number
NCT02428491
Brief Title
Immunogenicity and Safety of Sanofi Pasteur's Combined Vaccine Given as a Three-Dose Primary Series at 2, 3,4 Months of Age and Followed by a Booster Dose Given at 16 to 17 Months of Age in Vietnamese Infants Who Previously Received a Dose of Hepatitis B Vaccine at Birth or Within 1 Week After Birth
Official Title
Immunogenicity and Safety of Sanofi Pasteur's DTaP-IPV-Hep B-PRP-T Combined Vaccine Given as a Three-Dose Primary Series at 2, 3, and 4 Months of Age and Followed by a Booster Dose Given at 16 to 17 Months of Age in Vietnamese Infants Who Previously Received a Dose of Hepatitis B Vaccine at Birth or Within 1 Week After Birth
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
April 20, 2015 (Actual)
Primary Completion Date
January 11, 2017 (Actual)
Study Completion Date
January 11, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi Pasteur, a Sanofi Company

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to describe the immunogenicity and safety of Sanofi Pasteur's DTaP-IPV-Hep B-PRP-T fully liquid combined hexavalent vaccine (Hexaxim®) administered at 2, 3, and 4 months of age and at 16 to 17 months of age in infants and toddlers who received a dose of Hep B vaccine at birth or within 1 week after birth. Primary Objective: To describe the safety profile after each and all doses of Sanofi-Pasteur's DTaP-IPV-Hep B-PRP-T combined vaccine in Vietnamese infants and toddlers. Secondary Objective: To demonstrate the non-inferiority of the immune response to all antigens induced by the study vaccine in Vietnamese infants one month after the third dose in a 3-dose primary series with the immune response to all antigens induced by the same study vaccine outside Vietnam. To evaluate the immunogenicity of the study vaccine one month after the 3-dose primary series. To describe the persistence of all antibodies before receipt of the booster vaccination. To evaluate the immunogenicity of the study vaccine one month after the booster.
Detailed Description
Participants will receive a total of 5 doses of Hep B: One dose of Hep B monovalent vaccine given at birth or within 1 week after birth followed by 3 doses of the Sanofi Pasteur's hexavalent vaccine given as primary series at 2, 3, and 4 months of age and then a booster dose at 16 to 17 months of age, to comply with Vietnamese vaccination recommendations.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diphtheria, Tetanus, Pertussis, Poliomyelitis, Hepatitis B, Haemophilus Influenzae Type b
Keywords
Diphtheria, Tetanus, Pertussis, Poliomyelitis, Hepatitis B, Haemophilus Influenzae Type b, DTaP-IPV-Hep B-PRP-T Combined Vaccine (Hexaxim®)

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Model Description
Participants in this trial were randomized in a 1:1 ratio in 2 cohorts. All participants in both cohorts received Sanofi Pasteur's DTaP-IPV-HB-PRP~T combined vaccine in a 3-dose Infant Series. Participants from Cohort 1 provided blood samples for immunogenicity assessment and were evaluated for safety and immunogenicity. Participants in Cohort 2 did not provide any blood samples for immunogenicity analysis and were evaluated for safety only.
Masking
None (Open Label)
Allocation
N/A
Enrollment
354 (Actual)

8. Arms, Groups, and Interventions

Arm Title
DTaP-IPV-HB-PRP~T Vaccine
Arm Type
Experimental
Arm Description
All participants will receive 3 doses of 0.5 mL DTaP-IPV-HB-PRP~T combined vaccine, intramuscularly, at 2, 3 and 4 months of age (primary series), followed by a booster dose approximately 12 months after the completion of the primary series (at 16 to 17 months of age).
Intervention Type
Biological
Intervention Name(s)
Hexaxim®
Other Intervention Name(s)
Hexyon®, Hexacima®
Intervention Description
DTaP-IPV-Hep B-PRP-T combined vaccine, 0.5 mL, Intramuscular
Primary Outcome Measure Information:
Title
Number of Participants Reporting Solicited Injection Site Reactions or Solicited Systemic Reactions
Description
Solicited injection site reactions: tenderness, erythema, and swelling (and extensive limb swelling for booster dose). Solicited systemic reactions: fever, vomiting, crying abnormal, drowsiness, appetite loss, and irritability
Time Frame
Within 7 days after vaccination
Secondary Outcome Measure Information:
Title
Number of Subjects With Seroprotection/Seroconversion/Vaccine Response After Infant Series in Cohort 1
Description
Seroconversion:4-fold increase in anti-Pertussis(PT)& anti-Filamentous hemagglutinin(FHA) antibody(Ab) concentrations from pre-vaccination to one month after first dose.Vaccine response:anti-PT/anti-FHA Ab concentrations in Enzyme Linked Immunosorbent Assay(ELISA) units(EU)/mL>=4*Lower Limit of Quantitation(LLOQ) if pre-vaccination concentration <4*LLOQ/>=pre-vaccination concentration if prevaccination concentrations>=4*LLOQ. Seroprotection:anti-Diphtheria &anti-Tetanus>=0.01 International Units(IU)/mL&>=0.1 IU/mL;anti-PT &anti-FHA>=2 EU/mL &>=8 EU/mL;anti-Polyribosyl Ribitol Phosphate(PRP)>=0.15 microgram per milliliter(mcg/mL) &>=1.0mcg/mL;anti-Polio types 1,2,&3>=8(1/dilution),anti-Hepatitis B>=10 mili-international units per mililiter(mIU/mL)&>=100 mIU/mL
Time Frame
Day 90 (1 month after third dose)
Title
Number of Subjects With Seroprotection/Seroconversion/Vaccine and Booster Response Before and After Booster Vaccination in Cohort 1
Description
Seroconversion:4-fold increase in anti-PT & anti-FHA Ab concentrations from pre-booster vaccination to 1 month after booster dose.Vaccine response post-booster vaccination:post-booster Ab concentrations>=4*LLOQ if pre-dose 1 Ab concentrations<4*LLOQ/post-booster Ab concentrations>=predose 1 Ab concentrations if pre-dose 1>=4*LLOQ. Booster response:>=4 fold Ab concentrations increase from pre-dose 4 to one-month post-dose 4 if one-month post-dose 3<4*LLOQ/>=2 fold Ab concentrations increase from pre-dose 4 to one-month post-dose 4 if pre-dose 4>=4*LLOQ.Seroprotection:anti-Diphtheria & anti-Tetanus>=0.01 IU/mL &>=0.1 IU/mL &>=1.0 IU/mL;anti-PRP >=0.15 mcg/mL &>=1.0 mcg/mL;anti-Polio types 1, 2, & 3>=8 (1/dilution),anti-Hepatitis B>=10 mIU/mL &>=100 mIU/mL
Time Frame
Day 425 (pre-booster) and Day 455 (1 month after booster dose)
Title
Geometric Mean Titers or Geometric Mean Concentrations of DTaP-IPV-HB-PRP~T Antibodies Before and After Infant Series in Cohort
Description
Geometric mean of concentrations of antibodies against PT, FHA, diphtheria, tetanus, PRP, poliovirus 1, 2 and 3, and Hep B
Time Frame
Day 90 (1 month after third dose)
Title
Geometric Mean Titers or Geometric Mean Concentrations of DTaP-IPV-HB-PRP~T Antibodies Before and After Booster Vaccination in Cohort 1
Description
Geometric mean of concentrations of antibodies against PT, FHA, diphtheria, tetanus, PRP, poliovirus 1, 2 and 3, and Hep B
Time Frame
Day 425 (pre-booster) and Day 455 (1 month after booster dose)
Title
Percentage of Subjects With Seroprotection/Seroconversion Rates after Infant Series in Cohort 1 and Group 3 of A3L15 (NCT01105559)
Description
Seroconversion defined as 4-fold increase in anti-PT & anti-FHA Ab concentrations from pre-vaccination to one month after first dose. Seroprotection defined as following: anti-Diphtheria & anti-Tetanus >=0.01 IU/mL; anti-PT & anti-FHA >=4EU/mL; anti-PRP >=0.15 mcg/mL; anti-Polio types 1, 2, & 3 >=8 (1/dilution), anti-Hepatitis B >=10 mIU/mL. Results observed in Group 3 of Study A3L15 (NCT00362336), a study conducted in South Africa where participants had been given DTaP-IPV-HB-PRP~T at 6, 10, and 14 weeks of age following Hep B vaccination at birth, were used as the non-inferiority reference value
Time Frame
Day 90 (1 month after third dose)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
61 Days
Maximum Age & Unit of Time
91 Days
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Aged 61 to 91 days on the day of the first study visit Born at full term of pregnancy (≥ 37 weeks) and with a birth weight ≥2.5 kg Informed consent form has been signed and dated by the parent(s) or other legally acceptable representative (and by an independent witness if required by local regulations) Subject and parent/legally acceptable representative are able to attend all scheduled visits and to comply with all trial procedures Have received one dose of Hep B vaccine at birth or within 1 week after birth (documented according to the national recommendations). Exclusion Criteria: Participation in the 4 weeks preceding the first trial vaccination or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure Receipt of any vaccine in the 4 weeks preceding the first trial vaccination or planned receipt of any other vaccine within the period from 8 days before to 8 days after each subsequent trial vaccination except for Bacille Calmette Guerin (BCG) vaccination (any administration of oral poliovirus vaccine (OPV) in the context of oral poliovirus vaccine-national immunization days (NIDs) does not fall within the scope of this exclusion criterion) Previous vaccination against diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B (except the dose of Hep B vaccine given at birth or within 1 week after birth) diseases or Haemophilus influenzae type b infection with either the trial vaccine or another vaccine (any administration of OPV in the context of OPV-NIDs does not fall within the scope of this exclusion criterion) Past or current receipt of immune globulins, blood or blood-derived products or planned administration during the trial Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy since birth; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks since birth) History of diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, or Haemophilus influenzae type b infections (confirmed either clinically, serologically or microbiologically) Known personal or maternal history of Human Immunodeficiency Virus (HIV), or hepatitis C seropositivity Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine used in the trial or to a vaccine containing any of the same substances Known thrombocytopenia, as reported by the parent/legally acceptable representative Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination History of seizures In an emergency setting, or hospitalized involuntarily Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion Moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination or febrile illness (temperature ≥38.0°C). A prospective subject should not be included in the study until the condition has resolved or the febrile event has subsided Identified as a natural or adopted child of the Investigator, relatives or employee with direct involvement in the proposed study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Sanofi Pasteur SA
Official's Role
Study Director
Facility Information:
Facility Name
Preventive Medicine Centre of Thai Binh Province
City
Thai Binh
Country
Vietnam

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Links:
URL
http://www.sanofipasteur.com
Description
Related Info

Learn more about this trial

Immunogenicity and Safety of Sanofi Pasteur's Combined Vaccine Given as a Three-Dose Primary Series at 2, 3,4 Months of Age and Followed by a Booster Dose Given at 16 to 17 Months of Age in Vietnamese Infants Who Previously Received a Dose of Hepatitis B Vaccine at Birth or Within 1 Week After Birth

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