Phase III Study on Rotavirus Vaccine to Evaluate Lot-to-lot Consistency and Interference With Routine UIP Immunization

A Phase III, Multicenter, Open Label, Randomized Study of Bovine Rotavirus Pentavalent Vaccine (BRV-PV) to Evaluate Lot-To-Lot Consistency and to Investigate Potential Interference With Routine UIP Vaccinations in Healthy Infants in India.

This is a Phase 3, open-label, randomized study to evaluate lot-to-lot consistency in the manufacture of Bovine Rotavirus Pentavalent Vaccine (BRV-PV).

Study Overview

• Status: Completed
• Conditions: Rotavirus Gastroenteritis
• Intervention / Treatment: Biological: BRV-PV Lot A + DPT-HepB-Hib + OPV; Biological: BRV-PV Lot B + DPT-HepB-Hib + OPV; Biological: BRV-PV Lot C + DPT-HepB-Hib + OPV; Biological: ROTARIX + DPT-HepB-Hib + OPV

Detailed Description

The study is designed to evaluate lot-to-lot consistency in the manufacturing of Rotavirus vaccine by testing the vaccine in infants in order to demonstrate equivalence in the induction of specific anti-rotavirus IgA antibodies across three production lots. The study will also examine the potential interference of vaccine with UIP vaccines that will be administered concurrently by assessing non-inferiority in the immune responses to those vaccines when administered with / without the study vaccine.

• Study Type: Interventional
• Enrollment (Actual): 1500
• Phase: Phase 3

Contacts and Locations

Study Locations

• India
  • New Delhi, India
    • Maulana Azad Medical College
  • Andhra Pradesh
    • Hyderabad, Andhra Pradesh, India, 500020
      • Gandhi Medical College and Gandhi Hospital
    • Visakhapatnam, Andhra Pradesh, India, 530002
      • King George Hospital
  • Karnataka
    • Mysore, Karnataka, India, 570004
      • JSS Medical College and Hospital
  • Maharashtra
    • Mumbai, Maharashtra, India, 400008
      • T. N. Medical College and B. Y. L. Nair Charitable
    • Mumbai, Maharashtra, India, 400012
      • Seth G S Medical College & KEM Hospital
    • Pune, Maharashtra, India, 411043
      • Bharati Vidyapeeth Medical College and Hospital
    • Pune, Maharashtra, India, 412216
      • KEM Hospital and Research Centre, Vadu
  • Tamil Nadu
    • Chennai, Tamil Nadu, India, 600116
      • Sri Ramachandra Medical Centre
  • West Bengal
    • Kolkata, West Bengal, India, 700017
      • Institute of Child Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 1 month (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy infants as established by medical history and clinical examination before entering the study.
2. Age: 6-8 weeks at the time of enrollment.
3. Parental ability and willingness to provide written informed consent.
4. Parent who intends to remain in the area with the child during the study period.
5. Receipt of birth dose of Hepatitis B vaccine and OPV.

Exclusion Criteria:

1. Presence of diarrhea or vomiting in the previous 72 hours or on the day of enrollment (temporary exclusion).
2. Presence of fever on the day of enrollment (temporary exclusion).
3. Acute disease at the time of enrollment (temporary exclusion).
4. Concurrent participation in another clinical trial at any point throughout the entire timeframe for this study.
5. Presence of significant malnutrition or any systemic disorder as determined by medical history and / or physical examination which would compromise the subject's health or is likely to result in nonconformance to the protocol.
6. History of congenital abdominal disorders, intussusception, or abdominal surgery.
7. Known or suspected impairment of immunological function based on medical history and physical examination.
8. Household contact with an immunosuppressed individual or pregnant woman.
9. Prior receipt or intent to receive rotavirus and / or diphtheria, tetanus, pertussis, Haemophilus Influenzae type b, Hepatitis B vaccine (other than birth dose) or inactivated polio vaccine (IPV) during the study period and outside of the study. OPV dose received during national / subnational immunization days will be allowed.
10. A known sensitivity or allergy to any components of the study vaccine.
11. Clinically detectable congenital or genetic defect.
12. History of persistent diarrhea (defined as diarrhea that lasts 14 days or longer).
13. Receipt of any immunoglobulin therapy and / or blood products since birth or planned administration during the study period.
14. 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.
15. History of any neurologic disorders or seizures.
16. Any medical condition in the parents / infant which, in the judgment of the Investigator, would interfere with or serves as a contraindication to protocol adherence or a participant's parents' ability to give written informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1 - BRV-PV Lot A; BRV-PV Lot A + DPT- HepB-Hib + OPV	Biological: BRV-PV Lot A + DPT-HepB-Hib + OPV; Dose 1: 6-8 weeks, Dose 2: 10 week, Dose 3: 14 week
Experimental: Group 2 - BRV-PV Lot B; BRV-PV Lot B+ DPT- HepB-Hib + OPV	Biological: BRV-PV Lot B + DPT-HepB-Hib + OPV; Dose 1: 6-8 weeks, Dose 2: 10 week, Dose 3: 14 week; Other Names: Live Attenuated human-bovine reassortant pentavalent rotavirus vaccine
Experimental: Group 3 - BRV-PV Lot C; BRV-PV Lot C + DPT- HepB-Hib + OPV	Biological: BRV-PV Lot C + DPT-HepB-Hib + OPV; Dose 1: 6-8 weeks, Dose 2: 10 week, Dose 3: 14 week
Active Comparator: Group 4 - ROTARIX; ROTARIX + DPT-HepB-Hib + OPV	Biological: ROTARIX + DPT-HepB-Hib + OPV; Dose 1: 6-8 weeks, Dose 2: 10 week, Dose 3: 14 week (Third dose-Placebo)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rotavirus vaccine lots Immunogenicity	Serum anti- rotavirus IgA antibody concentrations expressed as GMCs for the BRV-PV to demonstrate equivalence in lot consistency among three lots.	Four weeks after the third dose of vaccination
Immunogenicity of UIP vaccines		Four weeks after the third dose of vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immediate adverse events and Solicited post -vaccination reactogenicity		AEs within 30 minutes post-vaccination and post vacc reactogenicity during 7 days after each vaccination
Rotavirus Immunogenicity:	Serum anti- rotavirus IgA antibody concentrations expressed as GMCs and proportion of subjects with post-vaccination IgA antibody concentration ≥20 U/ml for the comparison of BRV-PV vaccine and licensed rotavirus vaccine.	Four weeks after the third dose of vaccination

Collaborators and Investigators

• Sponsor: Serum Institute of India Pvt. Ltd.
• Collaborators: PATH
• Investigators: Study Director: Dr Prasad Kulkarni, M.D., Serum Institute of India Pvt. Ltd.

Publications and helpful links

General Publications

• Desai S, Rathi N, Kawade A, Venkatramanan P, Kundu R, Lalwani SK, Dubey AP, Venkateswara Rao J, Narayanappa D, Ghildiyal R, Gogtay NJ, Venugopal P, Palkar S, Munshi R, Bavdekar A, Juvekar S, Ganguly N, Niyogi P, Uttam KG, Kondekar A, Kumbhar D, Mohanlal S, Agarwal MC, Shetty P, Antony K, Gunale B, Dharmadhikari A, Deshpande J, Nalavade U, Sharma D, Bansal A, Tang Y, Flores J, Kulkarni PS. Non-interference of Bovine-Human reassortant pentavalent rotavirus vaccine ROTASIIL(R) with the immunogenicity of infant vaccines in comparison with a licensed rotavirus vaccine. Vaccine. 2018 Sep 5;36(37):5519-5523. doi: 10.1016/j.vaccine.2018.07.064. Epub 2018 Aug 10.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Actual): April 1, 2017
• Study Completion (Actual): June 1, 2017

Study Registration Dates

• First Submitted: October 6, 2015
• First Submitted That Met QC Criteria: October 21, 2015
• First Posted (Estimate): October 23, 2015

Study Record Updates

• Last Update Posted (Actual): September 11, 2018
• Last Update Submitted That Met QC Criteria: September 7, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: Rotavirus vaccine; BRV-PV; lot-to-lot consistency; interference with routine immunization
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: ROTA: 04 / VAC-020