Study Detail

Primary Outcome Measur(s):

- The proportion of infants achieving seroprotection against poliovirus types 1, 2, and 3, measured using blood samples will be for antibody assessment at 4 weeks after the third dose

- The proportion of infants achieving seroprotection against poliovirus types 1, 2, and 3, measured using blood samples will be for antibody assessment at 4 weeks after the third dose

- The proportion of infants achieving seroprotection against poliovirus types 1, 2, and 3, measured using blood samples will be for antibody assessment at 4 weeks after the fourth (booster) dose

Secondary outcome measure(s):

The proportion of infants achieving seroprotection against poliovirus types 1, 2, and 3, measured 4 using blood samples will be for antibody assessment at weeks after the third dose of the Hexavalent vaccine

1. All healthy full-term infants (born at 37 weeks) at 6-8 weeks old of either gender

2. Not planning to travel away during entire the study period (enrolment- approximately 294 days; 5 weeks – 42 weeks)

3. Parents resident of the study area for the last 3 months at the time of enrolment

4. Parent/guardian provides informed consent

1. Newborns found acutely ill at the time of enrolment and requiring emergent medical care/hospitalization.

2. Enrolment weight & height <-3 weight for height z-score

3. Infants with certain medical conditions i.e., syndromic infants, infants with petechial, purpura, or bleeding disorder (contraindication of intramuscular injections)

4. A diagnosis or suspicion of immunodeficiency disorder (either in the participant or in a member of the immediate family - e.g. several early infant deaths, a household member on chemotherapy) will render the newborn ineligible for the study

5. Diagnosed neurological disorder or a history of seizures or temperature >380C in last 3 days or any other indication of acute illness/infection within the past 7 days

6. Having a record of anaphylaxis or allergy to vaccine components

Title of the trial: Randomized Trial to Evaluate and Compare the immunogenicity and safety of the hexavalent vaccine in healthy infants in a polio-endemic Country.

Study Description:

This is an open-label, randomized controlled clinical trial designed to evaluate the safety and immunogenicity of a hexavalent vaccine in healthy infants in Pakistan. Polio remains endemic in Pakistan, and infants currently receive multiple separate vaccines, including pentavalent vaccine and inactivated polio vaccine (IPV). A new hexavalent vaccine combines protection against six diseases (diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type b, and polio) into a single injection. This study aims to assess whether the hexavalent vaccine is as effective and safe as the existing vaccination schedule, while potentially reducing the number of injections.

Healthy infants aged approximately 6 weeks will be enrolled and randomized into four study arms within two groups. Group I will receive vaccinations according to the national EPI schedule (6, 10, and 14 weeks, with a booster at 9 months), while Group II will receive vaccinations at 2, 4, and 6 months with a booster at 12 months. Participants will be followed for assessment of immune response and safety outcomes throughout the study duration.

The Clinical Trial Unit (CTU) of Aga Khan University Hospital in Karachi, Sindh, Pakistan will serve as the designated location for conducting the study. Infant participants will be enrolled at either 6 weeks in Group I or 8 weeks in Group II. The study will recruit participants from two peri-urban districts of Karachi, namely Cattle Colony and Ibrahim Hyderi, as well as the Aga Khan Hospital for Women and Children in Kharadar. These areas were selected as they represent a diverse population and will provide a reliable sample for the study. Written informed consent will be obtained from parents or legal guardians prior to enrollment, and the study will be conducted in accordance with applicable ethical and regulatory requirements.

Study Objectives:

Primary Objectives:

1. To compare the humoral immunity against type 1-3 poliovirus after administering 3 doses of the Hexavalent schedule (Arm A) and compare it with the national EPI schedule of pentavalent + IPV administered at 6, 10, and 14 weeks of age (Arm B)

2. To compare the humoral immunity against type 1-3 poliovirus after administering 3 doses of the Hexavalent schedule (Arm C) and compare it with routine immunization pentavalent + IPV administered at 2, 4, and 6 months of age (Arm D)

3. To compare the humoral immunity against type 1-3 poliovirus after administering 4 doses of the Hexavalent schedule given according to the national EPI schedule at 6, 10, 14 weeks, and 9 months of age (Group I) with Hexavalent doses given at 2, 4, 6, and 12 months of age (Group II)

Secondary objectives:

1. To evaluate the humoral immunity against type 1-3 poliovirus after administering the Hexavalent vaccine schedule at 6, 10, and 14 weeks (Arm A) and 2, 4, and 6-month schedule (Arm C).