The Efficacy of Oral Rotavirus Vaccine 116E (ROTAVAC 5D) in Chilean Infants (Rota5DCHILE)

The Efficacy of Three Doses of Live Attenuated, Oral Rotavirus Vaccine 116E (ROTAVAC 5D) in Chilean Infants.

This is a randomized, double-blind, phase 3 study to evaluate the Efficacy,Safety, and Immunogenicity of ROTAVAC 5D, a live attenuated rotavirus vaccine in healthy infants aged 6-8 weeks.

A total of 5800 healthy Chilean infants will be recruited in this study and randomized to receive either vaccine or placebo in 1:1 ratio. Among these participants 300 will be categorized to immunogenicity cohort, 150 from each group, and blood samples will be collected to assess the immune response.

Study Overview

• Status: Recruiting
• Conditions: Rotavirus Infection of Children
• Intervention / Treatment: Biological: ROTAVAC 5D; Other: Placebo

Detailed Description

The Efficacy of Three Doses of Live Attenuated, Oral Rotavirus Vaccine 116E (ROTAVAC 5D) in Chilean Infants.

This is a randomized, double-blind, phase 3 study to evaluate the Efficacy, Safety, and Immunogenicity of ROTAVAC 5D, a live attenuated rotavirus vaccine in healthy infants aged 6-8 weeks.

A total of 5800 healthy Chilean infants will be recruited in this study and randomized to receive either vaccine or placebo in 1:1 ratio. Among these participants 300 will be categorized to immunogenicity cohort, 150 from each group, and blood samples will be collected to assess the immune response. Inclusion At least one parent(s) or legally acceptable representative's consent for participation and are able to understand study procedures Subjects aged 6 to 8 weeks at recruitment No plans to move in the next 12 months Exclusion Administration of rotavirus vaccine in the past Presence of any illness requiring hospital referral (temporary exclusion) Known case of immunodeficiency disease, known HIV positive Known case of chronic gastroenteritis disease, chronic pulmonary disease, chronic renal disease, congenital heart disease Any other conditions which in the judgment of the investigator warrant exclusion (e.g. no exclusion criteria but seems 'ill', investigators suspects neglect) Diarrhea on the day of enrollment (temporary exclusion) A known sensitivity or allergy to any components of the study vaccines. Major congenital or genetic defect. Has received any immunoglobulin therapy and/or blood products since birth. 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, at the discretion of the principal investigator. Blood samples: In the "Immunogenicity Subset", 3 ml blood specimens will be collected at baseline and 28 (+) 5 days after the third dose of the Test Article/placebo to assess the anti rotavirus IgA antibody titer. Stool Specimens: The study team will attempt to collect a stool specimen for every GE episode, preferably within the first 2 days after episode onset. The stool specimen may be collected up to 7 days after the last day of diarrhea. The stool specimens will be sent to the laboratory. If the episode is a suspected intussusception or vaccine associated gastroenteritis that has occurred within four weeks after each dose of the Test Article/placebo, the specimen will be sent to the laboratory immediately for rotavirus testing and typing. For all ELISA RV positive samples, an aliquot of the stool specimen will be assessed for 20 enteropathogens by multiplex-PCR panel and to identify the genotype of the virus.

• Study Type: Interventional
• Enrollment (Estimated): 5800
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Krishna Mohan, PhD; Phone Number: 04046454520; Email: Kmohan@bharatbiotech.com

Study Locations

• Chile
  • Puerto Montt, Chile, 5480000
    • Recruiting
    • Centro de Investigación vacunas Hospital de Puerto Montt
    • Contact: Twele Montecinos Loreto Isabel, MBBS; Phone Number: +56652362450; Email: loreto.twele@gmail.com
  • Santiago, Chile, 5290000
    • Recruiting
    • CESFAM Lo Barnechea
    • Contact: Passalacqua Stephania, MBBS; Phone Number: +56978620320; Email: steph.passalacqua@gmail.com
  • Santiago, Chile, 5480000
    • Recruiting
    • CESFAM Santa julia
    • Contact: Jaldin Tapia Daniza Pamela; Phone Number: +56979963817; Email: djaldin2010@gmail.com
  • Santiago, Chile, 8380418
    • Recruiting
    • Hospital de Niños Roberto del Rio
    • Contact: Lucero Alvarez Yalda Cecilia, MBBS; Phone Number: +56997330860; Email: ylucero@gmail.com
  • Santiago, Chile, 9340000
    • Recruiting
    • CESFAM Esmeralda
    • Contact: George Sergio, MBBS; Phone Number: +56982488403; Email: sergio.george@gmail.com
  • Santiago, Chile, 9350079
    • Recruiting
    • CESFAM Colina
    • Contact: George Sergio, MBBS; Phone Number: +56982488403; Email: sergio.george@gmail.com
  • Santiago, Chile
    • Recruiting
    • CESFAM Lo Barnechea
    • Contact: Pletikosic Contreras, Ximena, MBBS; Phone Number: +56994035428; Email: ximepleti@hotmail.com
  • Santiago, Chile
    • Recruiting
    • Hospital Exequiel Gónzalez Cortés
    • Contact: Villena Martinez Rodolfo, MBBS; Phone Number: +56225765805; Email: rodolfo.villena@gmail.com
  • Valparaíso, Chile, 2340319
    • Recruiting
    • CESFAM Jean y Marie Thierry de Valparaíso
    • Contact: Gonzalez Marcela; Phone Number: +56996810739; Email: marcegl@gmail.com
  • Viña Del Mar, Chile, 2520000
    • Recruiting
    • Hospital Gustavo Fricke
    • Contact: Ducasse Crespo Karen, MBBS; Phone Number: +56998711747; Email: karenducasse@yahoo.es

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. At least one parent(s) or legally acceptable representative's consent for participation and are able to understand study procedures
2. Subjects aged 6 to 8 weeks at recruitment
3. No plans to move in the next 12 months

Exclusion Criteria:

1. Administration of rotavirus vaccine in the past
2. Presence of any illness requiring hospital referral (temporary exclusion)
3. Known case of immunodeficiency disease, known HIV positive
4. Known case of chronic gastroenteritis disease, chronic pulmonary disease, chronic renal disease, congenital heart disease
5. Any other conditions which in the judgment of the investigator warrant exclusion (e.g. no exclusion criteria but seems 'ill', investigators suspects neglect)
6. Diarrhea on the day of enrollment (temporary exclusion)
7. A known sensitivity or allergy to any components of the study vaccines.
8. Major congenital or genetic defect.
9. Has received any immunoglobulin therapy and/or blood products since birth.
10. 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, at the discretion of the principal investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rotavac 5D; Rotavirus Vaccine (ROTAVAC 5D), is a monovalent vaccine containing suspension of live attenuated rotavirus 116E prepared in Vero cells, containing NLT 10 power 5.0 FFU and administered as a three-dose regimen, 4 weeks apart.	Biological: ROTAVAC 5D; Rotavirus Vaccine (ROTAVAC 5D), is a monovalent vaccine containing suspension of live attenuated rotavirus 116E prepared in Vero cells, containing NLT 105.0 FFU and administered as a three-dose regimen, 4 weeks apart.
Placebo Comparator: Placebo; Placebo administered as a three-dose regimen, 4 weeks apart.	Other: Placebo; Placebo is administered as three doses 4 weeks apart

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the efficacy of ROTAVAC5D	Efficacy of ORV 116E in comparison to a placebo against moderate-severe rotavirus gastroenteritis defined as: episode of diarrhea (the passage of three or more loose or watery stools within a 24-hour period), with or without vomiting, that requires overnight hospitalization or rehydration therapy equivalent to World Health Organization (WHO) plan B (oral rehydration therapy) or plan C (intravenous rehydration therapy) in a medical facility such as a hospital, clinic, or supervised rural health care center	14 days following the 3rd dose till the age of 1 year (12 months) + up to 14 days].

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of Severe rotavirus gastroenteritis (>11 on the 20 point Vesikari scoring scale) caused by non vaccine rotavirus occurring at least 14 days following the third dose	Severe rotavirus gastroenteritis (>11 on the 20 point Vesikari scoring scale) caused by non vaccine rotavirus occurring at least 14 days following the third dose	Till the age of 12 months + up to 14 days
To evaluate the efficacy of a ROTAVAC 5D against any severity of rotavirusgastroenteritis	Any severity of gastroenteritis caused by non vaccine rotavirus from 14 days following the 3rd dose	Till the age of 1 year (12 months) + up to 14 days
To evaluate the efficacy of ROTAVAC 5D for rotavirus only gastroenteritis (absence of co-pathogens)	All primary and secondary endpoints indicated above for episodes that result positive only for rotavirus, and no other co-pathogen.	Throughout study period i.e.,30 months
To evaluate the efficacy of a ROTAVAC 5D against any severity of gastroenteritis irrespective of etiology	Any severity of gastroenteritis irrespective of etiology from 14 days following the 3rd dose	till the age of 1 year (12 months) + up to 14 days
To evaluate the efficacy of ROTAVAC 5D against severe (>11 on the 20 point Vesikari scoring scale) gastroenteritis irrespective of etiology	Severe (>11 on the 20 point Vesikari scoring scale) gastroenteritis irrespective of etiology f	From 14 days following the 3rd dose till the age of 1 year (12months) + up to 14 days
To evaluate the intent to treat efficacy of ROTAVAC 5D against severe rotavirus gastroenteritis	Severe rotavirus gastroenteritis (≥11 on the 20 point Vesikari scoring scale) caused by non vaccine rotavirus in the intent-to-treat population	till the age of 1 year (12 months) + up to 14 days
Safety of the subjects during study period To assess the safety of ROTAVAC 5D for immediate and seven day adverse events, after all the 3 doses	During this period, will be solicited adverse events till 30 minutes after each vaccination (immediate solicited adverse events) and adverse events occurring within 7 days after each vaccination.	From the day of vaccine administration to 7 days for all the three doses.
To assess the safety of ROTAVAC 5D for adverse events in the 4-week period following administration of each of the three doses of the vaccine/placebo	Unsolicited adverse events assessed from day 0 to 28 following each dose in comparison to a placebo will be assessed in a subset of subjects	day 0 to 28 following each dose
To assess the safety of ROTAVAC 5D for SAEs,especially intussusception events occurring during the study period in all subjects	SAEs with a special focus on Intussusception events in comparison to a placebo will be assessed in all subjects throughout the study period.	from day of 1st dose till the age of 1 year (12 months) + up to 14 days
Secondary Objectives (Immunogenicity)	Immunogenicity rates after three doses of the ROTAVAC 5D in comparison to a placebo will be ascertained in approximately 150 subjects in each group assessed by fourfold rise in rotavirus-specific serum IgA antibody titers.	Day 28 (+) 5 days after the third dose in comparison to baseline levels

Collaborators and Investigators

• Sponsor: Bharat Biotech International Limited
• Investigators: Study Director: Dr.V.Krishna Mohan, PhD, Bharat Biotech International Limited

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2023
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): February 1, 2025

Study Registration Dates

• First Submitted: December 11, 2023
• First Submitted That Met QC Criteria: January 9, 2024
• First Posted (Actual): January 11, 2024

Study Record Updates

• Last Update Posted (Actual): January 11, 2024
• Last Update Submitted That Met QC Criteria: January 9, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Reoviridae Infections; Rotavirus Infections
• Other Study ID Numbers: BBIL/Rotavac 5D-CHILE /2022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No