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

December 17, 2020 updated by: Roma Chilengi, Centre for Infectious Disease Research in Zambia

An Open-label, Randomized, Controlled, Single Centre, Phase IIb Study to Assess the Immunogenicity, Reactogenicity and Safety of Three Live Oral Rotavirus Vaccines, ROTAVAC® , ROTAVAC 5CM and Rotarix® in Healthy Zambian Infants

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

450

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Zambia
      • Lusaka, Zambia, 10101
        • George Research Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 month to 1 month (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ROTAVAC 5D
Bharat Biotech International Ltd's new Rotavirus vaccine, ROTAVAC 5D is a live, attenuated G9P[11] monovalent vaccine at a dose of 0.5mL containing NLT log 10^5.0 focus forming units (FFU) per dose. 5D is in liquid form.
Biological: ROTAVAC 5D
0.5 ml of the vaccine will be administered orally thrice at 6, 10 and 14 weeks of age.
Experimental: ROTAVAC®
Bharat Biotech International Ltd's licensed rotavirus vaccine, ROTAVAC® is a live, attenuated G9P[11] monovalent vaccine at a dose of 0.5mL containing NLT log 10^5.0 focus forming units (FFU) per dose. ROTAVAC® is in frozen form and is thawed till fully liquid prior to administration.
Biological: ROTAVAC®
0.5 ml of the vaccine will be administered orally thrice at 6, 10 and 14 weeks of age.
Active Comparator: Rotarix®
GSK Biologicals' licensed rotavirus vaccine, Rotarix® is a live attenuated RIX4414 strain of human rotavirus of the G1P[8] type containing not less than 106.0 CCID50 (cell culture infectious dose 50%) of the RIX 4414 strain of human rotavirus.
Biological: Rotarix®
1.5 ml of the liquid vaccine will be administered orally twice at 6 and 10 weeks of age.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Geometric Mean Concentration Using WC3 as the Viral Lysate
Time Frame: 28 day after last dose of the study vaccine
GMC of serum anti-rotavirus IgA antibodies as measured by enzyme linked immunosorbent assay (ELISA) using WC3 (heterologous to vaccine strain) as the viral lysate. WC3 strain of rotavirus used in the ELISA assay was heterologous to the 116E strain contained in the vaccines ROTAVAC 5D® and ROTAVAC®.
28 day after last dose of the study vaccine

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Immediate Adverse Events
Time Frame: within 30 minutes' post-vaccination.
Percentage of participants reporting immediate adverse events after each vaccination
within 30 minutes' post-vaccination.
Solicited Adverse Events
Time Frame: 7 day period after each vaccination.
Percentage of participants reporting solicited post-vaccination reactogenicity (fever, diarrhea, vomiting, decreased appetite, irritability, decreased activity level)
7 day period after each vaccination.
Unsolicited Adverse Events
Time Frame: From first vaccination through 4 weeks after the last vaccination.
Percentage of participants reporting unsolicited AEs at a rate >5%.
From first vaccination through 4 weeks after the last vaccination.
Serious Adverse Events
Time Frame: From first vaccination through 4 weeks after the last vaccination of each study participant. Immunogenicity
Percentage of participants reporting SAEs
From first vaccination through 4 weeks after the last vaccination of each study participant. Immunogenicity
Seroconversion Rate in Each of the Three Arms as Measured by ELISA Using WC3 as the Viral Lysate
Time Frame: 28 days after last dose of study vaccine.

Seroconversion is defined as a post-vaccination serum anti-rotavirus IgA antibody concentration of at least 20 U/mL if a baseline concentration is < 20 U/mL or a post-vaccination serum anti-rotavirus IgA antibody concentration of ≥ 2-fold baseline level if a baseline concentration is ≥ 20 U/mL.

WC3 strain of rotavirus used in the ELISA assay was heterologous to the 116E strain contained in the vaccines ROTAVAC® and ROTAVAC 5D®.
28 days after last dose of study vaccine.
Seropositivity Rate in Each of the Three Vaccine Arms as Measured by ELISA Using WC3 as the Viral Lysate
Time Frame: 28 days after last dose of study vaccine
Seropositivity is defined as serum anti-rotavirus IgA antibody concentration ≥ 20 U/mL. WC3 strain of rotavirus used in the ELISA assay was heterologous to the 116E strain contained in the vaccines ROTAVAC® and ROTAVAC 5D®.
28 days after last dose of study vaccine
Seroresponse Rate in Each of the Three Vaccine Arms as Measured by ELISA Using WC3 as the Viral Lysate
Time Frame: 28 days after last dose of study vaccine
Seroresponse will be assessed as a four-fold, three-fold and two- fold rise in antibody concentration from baseline. Seroresponse will be assessed as a four-fold, three-fold and two-fold rise in antibody concentration from baseline. WC3 strain of rotavirus used in the ELISA assay was heterologous to the 116E strain contained in the vaccines ROTAVAC® and ROTAVAC 5D®.
28 days after last dose of study vaccine
Geometric Mean Fold Rise (GMFR) in Each of the Three Vaccine Arms as Measured by ELISA Using WC3 as the Viral Lysate
Time Frame: At 28 days after last dose of study vaccine in reference to baseline.
GMFR in each of the ROTAVAC 5D®, ROTAVAC® and Rotarix® vaccine arms. WC3 strain of rotavirus used in the ELISA assay was heterologous to the 116E strain contained in the vaccines ROTAVAC® and ROTAVAC 5D®.
At 28 days after last dose of study vaccine in reference to baseline.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Geometric Mean Concentrations Using Strain 89-12 as the Viral Lysate
Time Frame: 28 days after the last dose of a study vaccine.
GMCs of serum anti-rotavirus IgA antibodies in each of the three vaccine arms. 89-12 strain of Rotavirus used in the ELISA assay was homologous to Rotarix® and was heterologous to the strain contained in ROTAVAC® and ROTAVAC 5D®.
28 days after the last dose of a study vaccine.
Seroconversion Using Strain 89-12 as the Viral Lysate
Time Frame: 28 days after the last dose of a study vaccine.
Seroconversion rate in three vaccine arms. 89-12 strain of Rotavirus used in the ELISA assay was homologous to Rotarix® and was heterologous to the strain contained in ROTAVAC® and ROTAVAC 5D®.
28 days after the last dose of a study vaccine.
Seropositivity Using Strain 89-12 as the Viral Lysate
Time Frame: at baseline and 28 days after last dose of study vaccine
Seropositivity rate in three vaccine arms. 89-12 strain of Rotavirus used in the ELISA assay was homologous to Rotarix® and was heterologous to the strain contained in ROTAVAC® and ROTAVAC 5D®.
at baseline and 28 days after last dose of study vaccine
Geometric Mean Fold Rise (GMFR) Using Strain 89-12 as the Viral Lysate
Time Frame: at 28 days after last dose of study vaccine in reference to baseline.
GMFR in the three vaccine arms. 89-12 strain of Rotavirus used in the ELISA assay was homologous to Rotarix® and was heterologous to the strain contained in ROTAVAC® and ROTAVAC 5D®.
at 28 days after last dose of study vaccine in reference to baseline.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre for Infectious Disease Research in Zambia

Collaborators

Children's Hospital Medical Center, Cincinnati
PATH
Bharat Biotech International Limited
Christian Medical College, Vellore, India

Investigators

  • Study Director: Niraj Rathi, MD, PATH

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 22, 2019

Primary Completion (Actual)

October 4, 2019

Study Completion (Actual)

October 4, 2019

Study Registration Dates

First Submitted

July 18, 2018

First Submitted That Met QC Criteria

July 18, 2018

First Posted (Actual)

July 26, 2018

Study Record Updates

Last Update Posted (Actual)

December 19, 2020

Last Update Submitted That Met QC Criteria

December 17, 2020

Last Verified

December 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CVIA 066

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Diarrhea

Clinical Trials on ROTAVAC 5D

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Macedonia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe