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

Phase 3

Completed

• Conditions: Pertussis; Hepatitis B; Tetanus; Diphtheria; Haemophilus Influenzae Type b; Poliomyelitis

• Registration Number: NCT02428491
• Lead Sponsor: Sanofi Pasteur, a Sanofi Company

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.

Study Timeline

• Study Start: 2015-04-20
• Study First Submitted: 2015-04-23
• Study First Submitted QC: 2015-04-23
• Study First Posted: 2015-04-28
• Primary Completion: 2017-01-11
• Study Completion: 2017-01-11
• Status Verified: 2022-03
• Last Update Submitted: 2022-03-24
• Last Update Posted: 2022-04-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 354

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Number of Participants Reporting Solicited Injection Site Reactions or Solicited Systemic Reactions	Within 7 days after vaccination	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

Name	Time	Method
Number of Subjects With Seroprotection/Seroconversion/Vaccine and Booster Response Before and After Booster Vaccination in Cohort 1	Day 425 (pre-booster) and Day 455 (1 month after booster dose)	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	Day 90 (1 month after third dose)	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)	Day 90 (1 month after third dose)	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
Number of Subjects With Seroprotection/Seroconversion/Vaccine Response After Infant Series in Cohort 1	Day 90 (1 month after third dose)	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
Geometric Mean Titers or Geometric Mean Concentrations of DTaP-IPV-HB-PRP~T Antibodies Before and After Booster Vaccination in Cohort 1	Day 425 (pre-booster) and Day 455 (1 month after booster dose)	Geometric mean of concentrations of antibodies against PT, FHA, diphtheria, tetanus, PRP, poliovirus 1, 2 and 3, and Hep B

Trial Locations

Locations (1)

Preventive Medicine Centre of Thai Binh Province; 🇻🇳 Thai Binh, Vietnam

Preventive Medicine Centre of Thai Binh Province

🇻🇳Thai Binh, Vietnam