Study of BBIL's ROTAVAC® and ROTAVAC 5CM Vaccines in Zambia

The study is being conducted to evaluate and compare the immunogenicity of ROTAVAC® and ROTAVAC 5D 28 days after the last dose of the vaccine, when administered to infants in a three-dose schedule at 6, 10 and 14 weeks of age.

The study will also assess the reactogenicity of the vaccine 7 days after each vaccination and safety from first vaccination up to 4 weeks after the last vaccination with ROTAVAC® and ROTAVAC 5D, and of Rotarix® when administered to infants in a two-dose schedule at 6 and 10 weeks of age.

This study is designed as a Phase IIb, single center, randomized, controlled, open label study with 3 groups of infants (n=150 per group) receiving either three doses of ROTAVAC® three doses of ROTAVAC 5D or two doses of Rotarix®. 450 participants will be randomized (1:1:1) to receive ROTAVAC®, ROTAVAC 5D or Rotarix®. The three doses of ROTAVAC® and ROTAVAC 5D will be administered at 6, 10 and 14 weeks of age whereas two doses of Rotarix® will be administered at 6 and 10 weeks of age. All vaccines will be administered concomitantly with EPI vaccines including Diphtheria, Tetanus, Pertussis, Haemophilus influenzae type b and Hepatitis B vaccine (DTwP-Hib-HepB), Pneumococcal conjugate vaccine and OPV at 6, 10 and 14 weeks and IPV at week 14 (when switched to in Zambia). The participants will be monitored for 30 minutes following vaccine administration for immediate adverse events.

A blood sample will be obtained from all the participating infants before first vaccination and four weeks after the last vaccine dose. This would mean that the blood sample will be collected at approximately 14 weeks of age for infants in the Rotarix® arm and 18 weeks for infants in the ROTAVAC® groups.

Enhanced passive/Active surveillance for vaccine reactogenicity (solicited reactions) over the 7-day period after each vaccination will be conducted on all infants. In addition, surveillance for unsolicited AEs, SAEs including intussusception will be carried out over the period between first vaccination and four weeks after the last vaccination on all infants.

The study will compare the immunogenicity of the two formulations of ROTAVAC® i.e. ROTAVAC® vs. ROTAVAC 5D and will descriptively analyze the immune response to Rotarix®. Primary immunogenicity analysis of all samples will be based on a validated ELISA which uses strain WC3 as a substrate. A subset of the samples (50 pairs/arms) collected will also be tested by a validated ELISA which uses strain 89-12 (G1P8 virus) as a substrate. This trial will generate immunogenicity and safety data on ROTAVAC® and ROTAVAC 5D outside of India. Presentation of data to Zambian Ministry of Health, WHO and in peer reviewed open access publications will be key audiences targeted for communication of results.

Eligibility Criteria:
Inclusion Criteria:

1. Healthy infant as established by medical history and clinical examination before entering the study.
2. Age: 6-8 weeks (42-56 days, both days inclusive) confirmed by Immunization Record.
3. Infants received age-appropriate EPI vaccines till enrolment.
4. Ability and willingness to provide informed consent as per local consenting procedures.
5. Parent can be contacted on phone and confirms intention to remain in the study area with the participant during the study period.

Exclusion Criteria:

1. Presence of diarrhea or vomiting in the previous 72 hours or on the day of enrolment (temporary exclusion).
2. Presence of fever on the day of enrolment (temporary exclusion).
3. Acute disease at the time of enrolment (temporary exclusion).
4. Concurrent participation in another clinical trial throughout the entire timeframe of this study.
5. Presence of severe malnutrition (weight-for-height z-score \< -3SD median).
6. Any systemic disorder (cardiovascular, pulmonary, hepatic, renal, gastrointestinal, hematological, endocrine, immunological, dermatological, neurological, cancer or autoimmune disease) as determined by medical history and/or physical examination which would compromise the child's health or is likely to result in non-conformance to the protocol.
7. History of congenital abdominal disorders, intussusception, abdominal surgery
8. Known or suspected impairment of immunological function based on medical history and physical examination.
9. Prior receipt or intent to receive rotavirus and other age specified EPI vaccines outside of the study center and during study participation.
10. A known sensitivity or allergy to any component of the study vaccine.
11. Clinically detectable significant congenital or genetic defect.
12. History of persistent diarrhea (defined as diarrhea more than 14 days).
13. Participant's parents not able, available or willing to accept active follow-up by the study staff.
14. Has received any immunoglobulin therapy and/or blood products since birth or planned administration during the study period.
15. History of chronic administration (defined as more than 14 days) of immunosuppressants including corticosteroids. Infants on inhaled or topical steroids may be permitted to participate in the study.
16. History of any neurologic disorders or seizures.
17. Any medical condition in the parents/infants that, in the judgment of the investigator, would interfere with or serves as a contraindication to protocol adherence or a participant's parent's/legally acceptable representative's ability to give informed consent.
18. Participant is a direct descendant (child or grandchild) of any person employed by the Sponsor, the CRO, the PI or study site personnel.