Study of DTaP-IPV-Hep B-PRP~T Combined Vaccine in Indian Infants Previously Given a Dose of Hepatitis B Vaccine at Birth

Hepatitis B Clinical Trial

Official title:

Immunogenicity and Safety of Sanofi Pasteur's DTaP-IPV-Hep B-PRP-T Combined Vaccine Given at 6, 10 and 14 Weeks of Age in Infants From India Who Previously Received a Dose of Hepatitis B Vaccine at Birth

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01948193
• Other study ID #: A3L33
• Secondary ID: U1111-1127-6936C
• Status: Completed
• Phase: Phase 3
• First received: September 18, 2013
• Last updated: September 29, 2015
• Start date: February 2014
• Est. completion date: June 2015

Study information

• Verified date: September 2015
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: India: Drugs Controller General of India
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to describe the immunogenicity and safety of a novel DTaP- IPV- Hep B-PRT~T fully liquid combined hexavalent vaccine (Hexaxim™) administered at 6, 10 and 14 weeks of age in infants born to mothers documented to be serum anti-hepatitis B surface antigen (HBsAg) serology negative in India.

Primary Objective:

• To evaluate the immunogenicity of the study vaccine in terms of seroprotection [diphtheria toxoid, tetanus toxoid, poliovirus types 1, 2 and 3, Haemophilus influenzae type b (Hib) polysaccharide (PRP), hepatitis B (Hep B)] and vaccine response for pertussis antigens [pertussis toxoid (PT) and filamentous haemagglutinin (FHA)] one month after the third dose.

Secondary Objectives:

• To further describe the immunogenicity of the study vaccine, before the first dose and one month after the third dose.

• To describe the safety after each and any doses of the study vaccine.

Description:

All participants will receive a total 4 doses of Hep B, i.e. one dose of Hep B monovalent vaccine given at birth followed by 3 doses of Sanofi Pasteur's hexavalent vaccine given at 6, 10 and 14 weeks of age in the context of the study. Participants and parents will attend four clinic visits; the expected participation in the study is approximately 3 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 177
• Est. completion date: June 2015
• Est. primary completion date: December 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 6 Weeks to 8 Weeks

Eligibility

Inclusion Criteria:

• Aged between 42-56 days (6 to 8 weeks) on the day of inclusion

• Born at full term of pregnancy (=37 weeks) and with a birth weight =2.5 kg

• Informed consent form signed by the parent(s) or any other legally acceptable representative

• Subject and parent/legally acceptable representative are able to attend all scheduled visits and to comply with all trial procedures

• Born to known hepatitis B surface antigen (HBsAg) seronegative mother (documented laboratory result of HBsAg assay from maternal blood sample performed during last trimester of pregnancy available)

• Have received one documented dose of Hep B vaccine and oral poliovirus vaccine (OPV) from birth as per national recommendations.

Exclusion Criteria:

• Participation in another clinical trial in the 4 weeks preceding the trial inclusion 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 (except Bacillus Calmette-Guerin [BCG] vaccine) or planned receipt of any other vaccine within the period from 8 days before to 8 days after each subsequent trial vaccination

• Previous vaccination against the diphtheria, tetanus, pertussis, poliomyelitis (expect the birth dose of OPV as per national recommendations) and hepatitis B (except the birth dose of Hep B vaccine) diseases or Hib infection with the trial vaccine or another vaccine

• 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 Hib 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 trial vaccine or a vaccine containing 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

• 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 (axillary temperature =38°C) on the day of inclusion (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

• History of seizures.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Diphtheria
• Hepatitis
• Hepatitis A
• Hepatitis B
• Invasive Hib Infections
• Poliomyelitis
• Tetanus
• Whooping Cough

Intervention

Biological:
• Hexaxim™: DTaP-IPV-Hep B-PRP~T combined vaccine
0.5 mL, Intramuscular

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi Pasteur, a Sanofi Company

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Seroprotection After Vaccinations With Sanofi Pasteur's DTaP-IPV-HB-PRP-T Combined Vaccine Following a Documented Dose of a Commercial Oral Poliovirus Vaccine and Recombinant Hep B Monovalent Vaccine at Birth	Diphtheria antibodies were measured by a toxin neutralization test, tetanus antibodies by an enzyme-linked immunosorbent assay (ELISA), Haemophilus influenzae type b polysaccharide (PRP) antibodies by Farr type radioimmunoassay, poliovirus 1, 2, and 3 antibodies by a neutralization assay, and Hepatitis B (Hep B) antibodies were measured by VITROS ECi/ECiQ Immunodiagnostic System.; Description of seroprotection: Diphtheria and Tetanus antibody concentrations =0.01 International Units (IU)/mL; Poliovirus 1, 2, and 3 titers =8 (1/dilution); Hep B concentrations =10 mIU/mL, and PRP =0.15 µg/mL.	Pre-dose 1 to one month post-dose 3	No
Primary	Percentage of Participants With Vaccine Response After Vaccinations With Sanofi Pasteur's DTaP-IPV-HB-PRP-T Combined Vaccine Following a Documented Dose of a Commercial Oral Poliovirus Vaccine and Recombinant Hep B Monovalent Vaccine at Birth	Anti-pertussis toxin (PT) and anti-filamentous hemagglutinin (FHA) antibodies were measured with an ELISA. Vaccine response was defined as percentage of participants with post-dose 3 anti-PT and anti-FHA antibody concentrations in ELISA units (EU)/mL = 4 x Lower Limit of Quantification (LLOQ) if pre-vaccination concentration was < 4 x LLOQ or = pre-vaccination concentration if pre-vaccination concentrations = 4 x LLOQ.	Pre-dose 1 to one month post-dose 3	No
Secondary	Percentage of Participants With Seroprotection Before and After Vaccinations With Sanofi Pasteur's DTaP-IPV-HB-PRP-T Combined Vaccine Following a Documented Dose of a Commercial Oral Poliovirus Vaccine and Recombinant Hep B Monovalent Vaccine at Birth	Diphtheria antibodies were measured by a toxin neutralization test, tetanus antibodies by an enzyme-linked immunosorbent assay (ELISA), Haemophilus influenzae type b polysaccharide (PRP) antibodies by Farr type radioimmunoassay, poliovirus 1, 2, and 3 antibodies by a neutralization assay, and Hepatitis B (Hep B) antibodies were measured by VITROS ECi/ECiQ Immunodiagnostic System.; Description of seroprotection: Diphtheria and Tetanus antibody concentrations =0.01 International Units (IU)/mL; Poliovirus 1, 2, and 3 titers =8 (1/dilution); Hep B concentrations =10 mIU/mL, and PRP =0.15 µg/mL.	Pre-dose 1 to one month post-dose 3	No
Secondary	Geometric Mean Titers of Antibodies Against Vaccine Antigens After Vaccinations With Sanofi Pasteur's DTaP-IPV-HB-PRP-T Combined Vaccine After a Documented Dose of an Oral Poliovirus Vaccine and Recombinant Hep B Monovalent Vaccine at Birth	Diphtheria antibodies were measured by a toxin neutralization test, tetanus, PT, and FHA antibodies by an ELISA, PRP antibodies by a Farr type radioimmunoassay, poliovirus 1, 2, and 3 antibodies by a neutralization assay, and Hep B antibodies were measured by VITROS ECi/ECiQ Immunodiagnostic System.	Pre-dose 1 to one month post-dose 3	No
Secondary	Geometric Mean Titer Ratios of Antibodies Against Vaccine Antigens After Vaccinations With Sanofi Pasteur's DTaP-IPV-HB-PRP-T Combined Vaccine After a Documented Dose of Oral Poliovirus Vaccine and Recombinant Hep B Monovalent Vaccine at Birth	Diphtheria antibodies were measured by a toxin neutralization test, PT and FHA antibodies by an ELISA, and Hep B antibodies were measured by VITROS ECi/ECiQ Immunodiagnostic System.	Pre-dose 1 to one month post-dose 3	No
Secondary	Percentage of Participants Reporting Solicited Injection-site or Systemic Reaction After Each Vaccination With Sanofi Pasteur's DTaP-IPV-HB-PRP-T Combined Vaccine Following a Documented Dose of Oral Poliovirus and Recombinant Hep B Vaccine at Birth	Injection-site reactions: Tenderness, Erythema, and Swelling. Systemic reactions: Fever, Vomiting, Crying abnormal, Drowsiness, Appetite lost, and Irritability. Grade 3 Injection site reactions: Tenderness, Cries when injected limb is moved, or reduced movement of injected limb; Erythema and Swelling, =50 mm. Grade 3 Systemic reactions: Fever, >39.5°C or >103.1°F; Vomiting, =6 episodes/24 hours or requires parenteral hydration; Crying abnormal, >3 hours; Drowsiness, Sleeping most of the time/difficult to wake up; Appetite lost, Refuses =3 or most feeds/meals; Irritability, Inconsolable.	Within 7 days after each vaccine injection	No

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