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

• ClinicalTrials.gov Identifier: NCT01305109
• Recruitment Status: Unknown
• First Posted: February 28, 2011
• Last Update Posted: June 12, 2012
• Sponsor: Bharat Biotech International Limited
• Collaborators: Ministry of Science and Technology, India; PATH
• Information provided by (Responsible Party): Bharat Biotech International Limited

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Viral Gastroenteritis Due to Rotavirus	Biological: ORV 116E; Biological: Placebo	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 6800 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: 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
• Study Start Date: March 2011
• Estimated Primary Completion Date: December 2013
• Estimated Study Completion Date: April 2014

Arms and Interventions

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 Name: 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

Outcome Measures

Primary Outcome Measures :

1. Efficacy against severe rotavirus gastroenteritis (>=11 on the 20 point Vesikari scoring scale) caused by non vaccine rotavirus [ Time Frame: Up to 2 years of age ]
   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.

Secondary Outcome Measures :

1. Efficacy against severe rotavirus gastroenteritis (>=11 on the 20 point Vesikari scoring scale) caused by non vaccine rotavirus [ Time Frame: Up to 1 year of age ]
   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
2. Efficacy against severe rotavirus gastroenteritis (>=11 on the 20 point Vesikari scoring scale) caused by non vaccine rotavirus [ Time Frame: From the age of 12 months till the age of 2 years of age ]
   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
3. Efficacy against severe rotavirus gastroenteritis (>=11 on the 20 point Vesikari scoring scale) caused by non vaccine rotavirus in intent-to-treat population [ Time Frame: Up to 2 years of age ]
   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.
4. Efficacy against any severity of gastroenteritis caused by a non vaccine rotavirus [ Time Frame: Up to 2 years of age ]
   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
5. Efficacy against any severity of gastroenteritis irrespective of etiology [ Time Frame: Up to 2 years of Age ]
   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
6. Efficacy against severe (>=11 on the 20 point Vesikari scoring scale) gastroenteritis irrespective of etiology [ Time Frame: Up to 2 years of age ]
   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
7. 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 [ Time Frame: Up to 2 years of age ]
   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
8. 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 [ Time Frame: Up to 2 years of age ]
   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
9. 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 [ Time Frame: Up to 2 years of age ]
   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
10. 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 [ Time Frame: Up to 2 years of age ]
    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
11. Efficacy against very severe rotavirus gastroenteritis (≥16 on the 20-point Vesikari scoring system) caused by non vaccine rotavirus [ Time Frame: Up to 2 years of age ]
    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
12. Safety of ORV 116E for immediate adverse events and serious adverse events in comparison to a placebo [ Time Frame: Up to 2 years of age ]
    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.
13. Safety of ORV 116E for adverse events in a subset [ Time Frame: 2 weeks period following each administration ]
    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
14. Safety of ORV 116E for intussusception events [ Time Frame: Up to 2 years of age ]
    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
15. 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 [ Time Frame: 28 days after administration of third dose ]
    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.

Eligibility Criteria

• Ages Eligible for Study: 6 Weeks to 7 Weeks (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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)

Contacts and Locations

Locations

India

Shirdi Sai Baba Rural Hospital, KEM Hospital Research Centre,Vadu Rural Health

Pune, Maharashtra, India, 412216

Centre for Health Research and Development, Society for Applied Studies

New Delhi, India, 110 062

Christian Medical College

Vellore, India, 632004

Sponsors and Collaborators

Bharat Biotech International Limited

Ministry of Science and Technology, India

PATH

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Bharat Biotech International Limited
• ClinicalTrials.gov Identifier: NCT01305109
• Other Study ID Numbers: BBIL/ROTA/021; Clinical Trials Registry-India ( Registry Identifier: CTRI/2010/091/000102 )
• First Posted: February 28, 2011
• Last Update Posted: June 12, 2012
• Last Verified: June 2012

Additional relevant MeSH terms:

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases