Safety and Immunogenicity Study of Live Attenuated Indian Rotavirus Vaccine Candidate Strains 116E and I321 in Infants

This study has been completed.
Sponsor:
Collaborators:
All India Institute of Medical Sciences, New Delhi
Stanford University
Indian Institute of Science
Children's Hospital Medical Center, Cincinnati
Ministry of Science and Technology, India
PATH
Information provided by:
Society for Applied Studies
ClinicalTrials.gov Identifier:
NCT00280111
First received: January 13, 2006
Last updated: July 1, 2008
Last verified: July 2008
  Purpose

It has been observed that in children who get a severe rotavirus infection, subsequent infections cause either no symptoms or generally only mild or moderate diarrhea. This evidence is the basis for developing a vaccine since it suggests that the first infection immunizes the child against disease upon re-infection.

It was found that neonatal avirulent strains 116E and I321 induce protective immunity and offer clinical protection for at least one year. Both these strains are well characterized and the safety studies have been done in animal models. These candidate vaccine strains have been evaluated for safety and immunogenicity in adults and children (2 to 12 years of age) by a randomized double blind placebo controlled trial in Cincinnati, USA. In India, the diversity of rotavirus strains is greater and there is greater prevalence of malnutrition and co-infection with other enteric pathogens. These vaccines have therefore, also been tested in India.


Condition Intervention Phase
Rotavirus Infections
Biological: 116E AGMK
Drug: I321
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Reactogenicity and Immunogenicity of Live Attenuated Indian Rotavirus Vaccine Candidate Strains 116E and I321 in Healthy Non-Malnourished Infants 8-12 Weeks of Age

Resource links provided by NLM:


Further study details as provided by Society for Applied Studies:

Primary Outcome Measures:
  • - Safety [ Time Frame: 4 weeks after test article administration ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • - Vaccine Take, antibody titers in subjects in vaccine and placebo groups 28 days after administration of vaccine/placebo or shedding of rotavirus vaccine strains by antigen detection ELISA on days 3, 7 and 28 post administration. [ Time Frame: 4 weeks post administration of test article ] [ Designated as safety issue: No ]

Enrollment: 90
Study Start Date: January 2005
Study Completion Date: May 2005
Primary Completion Date: May 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
116E AGMK
Biological: 116E AGMK
Single dose of 116E 10^5 FFu
Experimental: 2
I321 AGMK
Drug: I321
Single dose of I321 10^5 FFu
Placebo Comparator: 3
Placebo
Drug: Placebo
1 crystal of potassium permanganate dissolved in the bicarbonate buffer to colour match the vaccine

Detailed Description:

This study was a phase I randomized, double blind, safety and immunogenicity study of live, attenuated neonatal rotavirus vaccine candidate strains 116E or I321 in healthy non-malnourished infants aged 8-12 weeks. Informed, written, witnessed consent was obtained from the parents before infants were screened at 6 weeks of age. Infants (n=90) were randomized (30 per group) to receive one dose of either the 116E or I321 vaccines (10^5 fluorescence focus units, FFu) or placebo at 8 weeks of age. The rotavirus vaccine was administered at a different time than DPT (Diptheria-Pertussis-Tetanus), OPV (Oral Polio Vaccine) and HBV (Hepatitis B vaccine) immunization since the trial represented the first safety study in infants with these strains. The DPT, OPV and HBV vaccines were given at the regular EPI schedule of 6, 10 and 14 weeks with the precautions and techniques routinely in place for these.

The test article was administered orally two weeks after the first DPT, OPV and HBV dose, after half an hour of administering 2.5 ml bicarbonate to buffer stomach acidity.

Evaluation of reactogenicity consisted of daily recording of symptoms reported by the mother/caregiver and twice-daily axillary temperature measurements for 14 days post administration of vaccine/placebo. Stool specimens were collected before administration of vaccine/placebo, twice during the week following administration (days 3 and 7), and at day 28 after administration to evaluate for vaccine virus shedding. Weekly recording of adverse events was also done for the next 2 weeks i.e. on days 21 and 28 post administration of vaccine/placebo. If gastrointestinal signs or symptoms occurred any time during the 4 weeks observation period, attempts were made to collect stool samples daily (maximum 2 per day) while the illness persisted, to be examined for the presence of the vaccine strains.

Immunogenicity was determined by analysis of sera obtained before immunization and 28 days after immunization for changes in titers of rotavirus antibodies.

  Eligibility

Ages Eligible for Study:   8 Weeks to 12 Weeks
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy infants
  • Consent available

Exclusion Criteria:

  • Evidence of renal, cardiovascular, liver or other reticuloendothelial, neurological, gastrointestinal, hematologic, rheumatologic or immunologic disease
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00280111

Locations
India
Society for Applied Studies
New Delhi, Delhi, India, 110016
Sponsors and Collaborators
Society for Applied Studies
All India Institute of Medical Sciences, New Delhi
Stanford University
Indian Institute of Science
Children's Hospital Medical Center, Cincinnati
Ministry of Science and Technology, India
PATH
Investigators
Principal Investigator: Maharaj K Bhan, MD All India Institute of Medical Sciences, New Delhi
Principal Investigator: Pratima Ray, PhD All India Institute of Medical Sciences, New Delhi
  More Information

Publications:
Responsible Party: Dr. MK Bhan, Dr. Pratima Ray, All India Institute of Medical Sciences
ClinicalTrials.gov Identifier: NCT00280111     History of Changes
Other Study ID Numbers: 03-153, U01 AI 53719-02
Study First Received: January 13, 2006
Last Updated: July 1, 2008
Health Authority: India: Drugs Controller General of India

Keywords provided by Society for Applied Studies:
rotavirus
vaccine
safety
immunogenicity
infants

Additional relevant MeSH terms:
Rotavirus Infections
Reoviridae Infections
RNA Virus Infections
Virus Diseases

ClinicalTrials.gov processed this record on October 23, 2014