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

Viral Gastroenteritis Due to Rotavirus Clinical Trial

— ROTAVAC  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01305109
• Other study ID #: BBIL/ROTA/021
• Secondary ID: Clinical Trials
• Status: Active, not recruiting
• Phase: Phase 3
• First received: February 18, 2011
• Last updated: June 9, 2012
• Start date: March 2011
• Est. completion date: April 2014

Study information

• Verified date: June 2012
• Source: Bharat Biotech International Limited
• Contact: n/a
• Is FDA regulated: No
• Health authority: India: Drugs Controller General of India
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 6800
• Est. completion date: April 2014
• Est. primary completion date: December 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 6 Weeks to 7 Weeks

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Adenovirus Infections, Human
• Enteritis
• Enterovirus Infections
• Gastroenteritis
• Viral Gastroenteritis Due to Rotavirus

Intervention

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
• Placebo
3 doses of 0.5 mL at 4 week intervals

Locations

Country	Name	City	State
India	Centre for Health Research and Development, Society for Applied Studies	New Delhi
India	Shirdi Sai Baba Rural Hospital, KEM Hospital Research Centre,Vadu Rural Health	Pune	Maharashtra
India	Christian Medical College	Vellore

Sponsors (3)

Lead Sponsor	Collaborator
Bharat Biotech International Limited	Ministry of Science and Technology, India, PATH

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	No