Clinical trial NCT01305109: A Phase III Clinical Trial to Evaluate the Protective Efficacy of Three Doses of Oral Rotavirus Vaccine (ORV) 116E
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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Viral Gastroenteritis Due to Rotavirus
Lead sponsor: Bharat Biotech International Limited
Sponsor class: INDUSTRY
Collaborators: name: Ministry of Science and Technology, India
name: PATH
First posted: 2011-02-28
Enrollment: 6800
Sex: ALL
Minimum age (years): 6
Maximum age (years): 7
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility 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)

Primary outcomes:
measure: Efficacy against severe rotavirus gastroenteritis (>=11 on the 20 point Vesikari scoring scale) caused by non vaccine rotavirus
timeFrame: Up to 2 years of age
Secondary outcomes:
measure: Efficacy against severe rotavirus gastroenteritis (>=11 on the 20 point Vesikari scoring scale) caused by non vaccine rotavirus
timeFrame: Up to 1 year of age
measure: Efficacy against severe rotavirus gastroenteritis (>=11 on the 20 point Vesikari scoring scale) caused by non vaccine rotavirus
timeFrame: From the age of 12 months till the age of 2 years of age
measure: Efficacy against severe rotavirus gastroenteritis (>=11 on the 20 point Vesikari scoring scale) caused by non vaccine rotavirus in intent-to-treat population
timeFrame: Up to 2 years of age
measure: Efficacy against any severity of gastroenteritis caused by a non vaccine rotavirus
timeFrame: Up to 2 years of age
measure: Efficacy against any severity of gastroenteritis irrespective of etiology
timeFrame: Up to 2 years of Age
measure: Efficacy against severe (>=11 on the 20 point Vesikari scoring scale) gastroenteritis irrespective of etiology
timeFrame: Up to 2 years of age
measure: 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
timeFrame: Up to 2 years of age
measure: 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
timeFrame: Up to 2 years of age
measure: 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
timeFrame: Up to 2 years of age
measure: 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
timeFrame: Up to 2 years of age
measure: Efficacy against very severe rotavirus gastroenteritis (≥16 on the 20-point Vesikari scoring system) caused by non vaccine rotavirus
timeFrame: Up to 2 years of age
measure: Safety of ORV 116E for immediate adverse events and serious adverse events in comparison to a placebo
timeFrame: Up to 2 years of age
measure: Safety of ORV 116E for adverse events in a subset
timeFrame: 2 weeks period following each administration
measure: Safety of ORV 116E for intussusception events
timeFrame: Up to 2 years of age
measure: 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
timeFrame: 28 days after administration of third dose
Other outcomes:
Locations:
city: Pune
country: India
facility: Shirdi Sai Baba Rural Hospital, KEM Hospital Research Centre,Vadu Rural Health
state: Maharashtra
city: New Delhi
country: India
facility: Centre for Health Research and Development, Society for Applied Studies
city: Vellore
country: India
facility: Christian Medical College
Study officials:
affiliation: Centre for Health Research and Development, Society for Applied Studies
name: Dr. Temsunaro R Chandola, MD, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Christian Medical College, Vellore, India
name: Gagandeep Kang, MDFRCPathPhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Shirdi Sai Baba Rural Hospital, KEM Hospital Research Centre,Vadu Rural Health
name: Ashish Bavdekar, MD,DCH,DNB
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.