A Phase III Clinical Trial to Evaluate the Protective Efficacy of Three Doses of Oral Rotavirus Vaccine (ORV) 116E
- Conditions
- Viral Gastroenteritis Due to Rotavirus
- Interventions
- Biological: PlaceboBiological: ORV 116E
- Registration Number
- NCT01305109
- Lead Sponsor
- Bharat Biotech International Limited
- 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.
- 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 6800
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo 3 doses of 0.5 mL at 4 week intervals Oral Rotavirus Vaccine 116E (ORV 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
- Primary Outcome Measures
Name Time Method Efficacy against severe rotavirus gastroenteritis (>=11 on the 20 point Vesikari scoring scale) caused by non vaccine rotavirus 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
Name Time Method Efficacy against any severity of gastroenteritis caused by a non vaccine rotavirus 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
Efficacy against any severity of gastroenteritis irrespective of etiology 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
Efficacy against severe (>=11 on the 20 point Vesikari scoring scale) gastroenteritis irrespective of etiology 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
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 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
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 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
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 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
Efficacy against severe rotavirus gastroenteritis (>=11 on the 20 point Vesikari scoring scale) caused by non vaccine rotavirus 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
Efficacy against severe rotavirus gastroenteritis (>=11 on the 20 point Vesikari scoring scale) caused by non vaccine rotavirus in intent-to-treat population 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.
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 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
Efficacy against very severe rotavirus gastroenteritis (≥16 on the 20-point Vesikari scoring system) caused by non vaccine rotavirus 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
Safety of ORV 116E for immediate adverse events and serious adverse events in comparison to a placebo 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.
Safety of ORV 116E for adverse events in a subset 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
Safety of ORV 116E for intussusception events 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
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 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.
Trial Locations
- Locations (3)
Centre for Health Research and Development, Society for Applied Studies
🇮🇳New Delhi, India
Christian Medical College
🇮🇳Vellore, India
Shirdi Sai Baba Rural Hospital, KEM Hospital Research Centre,Vadu Rural Health
🇮🇳Pune, Maharashtra, India