A Phase III Clinical Trial to Evaluate the Protective Efficacy of Three Doses of Oral Rotavirus Vaccine (ORV) 116E (ROTAVAC)

A Phase III, Randomized, Double Blind, Placebo Controlled Trial to Evaluate the Protective Efficacy of Three Doses of Oral Rotavirus Vaccine (ORV) 116E, Against Severe Rotavirus Gastroenteritis in Infants

The trial is a phase III randomized, double-blind, placebo-controlled trial with the primary objective of evaluating the efficacy of three doses of ORV 116E, 10^5.0 FFU, against severe rotavirus gastroenteritis, in comparison with a placebo in India.

Study Overview

• Status: Unknown
• Conditions: Viral Gastroenteritis Due to Rotavirus
• Intervention / Treatment: Biological: ORV 116E; Biological: Placebo

Detailed Description

The trial is a phase III randomized, double-blind, placebo-controlled trial with the primary objective of evaluating the efficacy of three doses of ORV 116E, 10^5.0 FFU, against severe rotavirus gastroenteritis, in comparison with a placebo in India. The clinical trial is not a global trial. Three administrations of ORV 116E will be co-administered with childhood vaccines (which will include vaccines against diphtheria, pertussis, tetanus, Haemophilus influenzae B and Hepatitis B and OPV) at 6 to 7 weeks, greater than or equal to 10 weeks and greater than or equal to 14 weeks of age. 6800 subjects will be enrolled in three sites - Delhi, Pune (Maharashtra) and Vellore (Tamil Nadu) and followed up till the age of 2 years (24 months + up to 14 days). Multiple trial sites are included to ensure greater demographic distribution to obtain evidence of cross immunity and quicker recruitment of the necessary number of subjects. The subjects to be included from these sites would be representative of the population of India.

The protocol has been reviewed by the institutional review boards of the Society for Applied Studies (New Delhi), KEM Hospital Research Centre (Pune), Christian Medical College (Vellore). Ethics clearance has also been obtained from the Department of Biotechnology, Government of India and Western Institutional Review Board.

• Study Type: Interventional
• Enrollment (Anticipated): 6800
• Phase: Phase 3

Contacts and Locations

Study Locations

• India
  • New Delhi, India, 110 062
    • Centre for Health Research and Development, Society for Applied Studies
  • Vellore, India, 632004
    • Christian medical college
  • Maharashtra
    • Pune, Maharashtra, India, 412216
      • Shirdi Sai Baba Rural Hospital, KEM Hospital Research Centre,Vadu Rural Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 1 month (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• At least one parent(s) or legally acceptable representative's consent for participation and are able to understand study procedures
• Subjects aged 6 to 7 weeks at recruitment
• No plans to move in the next 24 months

Exclusion Criteria:

• 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
• 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)

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: Oral Rotavirus Vaccine 116E (ORV 116E); Oral Rotavirus Vaccine 116E (ORV 116E), 10^5.0 FFU of Bharat Biotech International Limited, 3 doses of 0.5 mL at 4 week intervals	Biological: ORV 116E; Oral Rotavirus Vaccine 116E (ORV 116E), 10^5.0 FFU of Bharat Biotech International Limited, 3 doses of 0.5mL at 4 week intervals; Other Names: ROTAVAC
Placebo Comparator: Placebo; 3 doses of 0.5 mL at 4 week intervals	Biological: Placebo; 3 doses of 0.5 mL at 4 week intervals

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy against severe rotavirus gastroenteritis (>=11 on the 20 point Vesikari scoring scale) caused by non vaccine rotavirus	Efficacy of ORV 116E will be assessed in comparison to a placebo against severe rotavirus gastroenteritis (>=11 on the 20 point Vesikari scoring scale) caused by non vaccine rotavirus in all subjects from 14 days following the 3rd dose till the age of 2 years (24 months) + up to 14 days.	Up to 2 years of age

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy against severe rotavirus gastroenteritis (>=11 on the 20 point Vesikari scoring scale) caused by non vaccine rotavirus	Efficacy of ORV 116E will be assessed in comparison to a placebo against 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	Up to 1 year of age
Efficacy against severe rotavirus gastroenteritis (>=11 on the 20 point Vesikari scoring scale) caused by non vaccine rotavirus	Efficacy of ORV 116E will be assessed in comparison to a placebo for severe rotavirus gastroenteritis (>=11 on the 20 point Vesikari scoring scale) caused by non vaccine rotavirus occurring from the age of 12 months till the age of 2 years (24 months) + up to 14 days	From the age of 12 months till the age of 2 years of age
Efficacy against severe rotavirus gastroenteritis (>=11 on the 20 point Vesikari scoring scale) caused by non vaccine rotavirus in intent-to-treat population	Efficacy of ORV 116E will be assessed in comparison to a placebo against 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 2 years (24 months) + up to 14 days.	Up to 2 years of age
Efficacy against any severity of gastroenteritis caused by a non vaccine rotavirus	Efficacy of ORV 116E will be assessed in comparison to a placebo for any severity of gastroenteritis caused by non vaccine rotavirus from 14 days following the 3rd dose till the age of 2 years (24 months) + up to 14 days	Up to 2 years of age
Efficacy against any severity of gastroenteritis irrespective of etiology	Efficacy of ORV 116E will be assessed in comparison to a placebo for any severity of gastroenteritis irrespective of etiology from 14 days following the 3rd dose till the age of 2 years (24 months) + up to 14 days	Up to 2 years of Age
Efficacy against severe (>=11 on the 20 point Vesikari scoring scale) gastroenteritis irrespective of etiology	Efficacy of ORV 116E will be assessed in comparison to a placebo for severe (≥11 on the 20 point Vesikari scoring scale) gastroenteritis irrespective of etiology from 14 days following the 3rd dose till the age of 2 years (24 months) + up to 14 days	Up to 2 years of age
Efficacy to prevent hospitalization and/or supervised rehydration therapy (equivalent to WHO plan B or C) in a treatment facility/hospital for gastroenteritis caused by non vaccine rotavirus	Efficacy of ORV 116E will be assessed in comparison to a placebo to prevent hospitalization and/or supervised re-hydration therapy (equivalent to WHO plan B or C) in a treatment facility/hospital for gastroenteritis caused by non vaccine rotavirus from 14 days following the 3rd dose till the age of 2 years (24 months) + up to 14 days	Up to 2 years of age
Efficacy to prevent hospitalization and/or supervised rehydration therapy (equivalent to WHO plan B or C) in a treatment facility/hospital for gastroenteritis of any etiology	Efficacy of ORV 116E will be assessed in comparison to a placebo to prevent hospitalization and/or supervised re-hydration therapy (equivalent to WHO plan B or C) in a treatment facility/hospital for gastroenteritis of any etiology from 14 days following the 3rd dose till the age of 2 years (24 months) + up to 14 days	Up to 2 years of age
Efficacy to prevent hospitalization and/or supervised re-hydration therapy (equivalent to WHO plan B or C) in a treatment facility/hospital for severe gastroenteritis caused by non vaccine rotavirus	Efficacy of ORV 116E will be assessed in comparison to a placebo to prevent hospitalization and/or supervised re-hydration therapy (equivalent to WHO plan B or C) in a treatment facility/hospital for severe gastroenteritis caused by non vaccine rotavirus from 14 days following the 3rd dose till the age of 2 years (24 months) + up to 14 days	Up to 2 years of age
Efficacy to prevent hospitalization and/or supervised re-hydration therapy (equivalent to WHO plan B or C) in a treatment facility/hospital for severe gastroenteritis of any etiology	Efficacy of ORV 116E will be assessed in comparison to a placebo to prevent hospitalization and/or supervised re-hydration therapy (equivalent to WHO plan B or C) in a treatment facility/hospital for severe gastroenteritis of any etiology from 14 days following the 3rd dose till the age of 2 years (24 months) + up to 14 days	Up to 2 years of age
Efficacy against very severe rotavirus gastroenteritis (≥16 on the 20-point Vesikari scoring system) caused by non vaccine rotavirus	Efficacy of ORV 116E will be assessed in comparison to placebo against very severe rotavirus gastroenteritis (≥16 on the 20-point Vesikari scoring system) caused by non vaccine rotavirus from 14 days following the 3rd dose till the age of 2 years (24 months) + up to 14 days	Up to 2 years of age
Safety of ORV 116E for immediate adverse events and serious adverse events in comparison to a placebo	Safety of ORV 116E for immediate adverse events and serious adverse events in comparison to a placebo will be assessed in all the subjects, from day of 1st dose till the age of 2 years (24 months) + up to 14 days.	Up to 2 years of age
Safety of ORV 116E for adverse events in a subset	Safety of ORV 116E for adverse events assessed daily in the 2 week period following each dose in comparison to a placebo in first one third of the enrolled subjects in all the three sites	2 weeks period following each administration
Safety of ORV 116E for intussusception events	Safety of ORV 116E for intussusception events in comparison to a placebo will be assessed in all subjects, from day of 1st dose till the age of 2 years (24 months) + up to 14 days	Up to 2 years of age
Immunogenicity rates to three doses of the ORV 116E and vaccine virus shedding rates after each of the three doses of the ORV 116E in a subset	Immunogenicity rates to three doses of the ORV 116E and vaccine virus shedding rates after each of the three doses of the ORV 116E in comparison to a placebo will be ascertained in approximately 150 subjects at each site.	28 days after administration of third dose

Collaborators and Investigators

• Sponsor: Bharat Biotech International Limited
• Collaborators: PATH; Ministry of Science and Technology, India
• Investigators: Principal Investigator: Dr. Temsunaro R Chandola, MD, MSc, Centre for Health Research and Development, Society for Applied Studies; Principal Investigator: Gagandeep Kang, MDFRCPathPhD, Christian Medical College, Vellore, India; Principal Investigator: Ashish Bavdekar, MD,DCH,DNB, Shirdi Sai Baba Rural Hospital, KEM Hospital Research Centre,Vadu Rural Health

Publications and helpful links

General Publications

• Bhandari N, Rongsen-Chandola T, Bavdekar A, John J, Antony K, Taneja S, Goyal N, Kawade A, Kang G, Rathore SS, Juvekar S, Muliyil J, Arya A, Shaikh H, Abraham V, Vrati S, Proschan M, Kohberger R, Thiry G, Glass R, Greenberg HB, Curlin G, Mohan K, Harshavardhan GV, Prasad S, Rao TS, Boslego J, Bhan MK; India Rotavirus Vaccine Group. Efficacy of a monovalent human-bovine (116E) rotavirus vaccine in Indian children in the second year of life. Vaccine. 2014 Aug 11;32 Suppl 1:A110-6. doi: 10.1016/j.vaccine.2014.04.079.
• Bhandari N, Rongsen-Chandola T, Bavdekar A, John J, Antony K, Taneja S, Goyal N, Kawade A, Kang G, Rathore SS, Juvekar S, Muliyil J, Arya A, Shaikh H, Abraham V, Vrati S, Proschan M, Kohberger R, Thiry G, Glass R, Greenberg HB, Curlin G, Mohan K, Harshavardhan GV, Prasad S, Rao TS, Boslego J, Bhan MK; India Rotavirus Vaccine Group. Efficacy of a monovalent human-bovine (116E) rotavirus vaccine in Indian infants: a randomised, double-blind, placebo-controlled trial. Lancet. 2014 Jun 21;383(9935):2136-43. doi: 10.1016/S0140-6736(13)62630-6. Epub 2014 Mar 12.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Anticipated): December 1, 2013
• Study Completion (Anticipated): April 1, 2014

Study Registration Dates

• First Submitted: February 18, 2011
• First Submitted That Met QC Criteria: February 25, 2011
• First Posted (Estimate): February 28, 2011

Study Record Updates

• Last Update Posted (Estimate): June 12, 2012
• Last Update Submitted That Met QC Criteria: June 9, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis
• Other Study ID Numbers: BBIL/ROTA/021; Clinical Trials Registry-India (Registry Identifier: CTRI/2010/091/000102)