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

Rotavirus Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00280111
• Other study ID #: 03-153
• Secondary ID: U01AI053719-02
• Status: Completed
• Phase: Phase 1
• First received: January 13, 2006
• Last updated: July 1, 2008
• Start date: January 2005
• Est. completion date: May 2005

Study information

• Verified date: July 2008
• Source: Society for Applied Studies
• Contact: n/a
• Is FDA regulated: No
• Health authority: India: Drugs Controller General of India
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: May 2005
• Est. primary completion date: May 2005
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 8 Weeks to 12 Weeks

Eligibility

Inclusion Criteria:

• Healthy infants

• Consent available

Exclusion Criteria:

• Evidence of renal, cardiovascular, liver or other reticuloendothelial, neurological, gastrointestinal, hematologic, rheumatologic or immunologic disease

Study Design

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

Related Conditions & MeSH terms

• Rotavirus Infections

Intervention

Biological:
• 116E AGMK
Single dose of 116E 10^5 FFu

Drug:
• I321
Single dose of I321 10^5 FFu
• Placebo
1 crystal of potassium permanganate dissolved in the bicarbonate buffer to colour match the vaccine

Locations

Country	Name	City	State
India	Society for Applied Studies	New Delhi	Delhi

Sponsors (9)

Lead Sponsor	Collaborator
Society for Applied Studies	All India Institute of Medical Sciences, New Delhi, Centers for Disease Control and Prevention, Children's Hospital Medical Center, Cincinnati, Indian Institute of Science, Ministry of Science and Technology, India, National Institutes of Health (NIH), PATH, Stanford University

Country where clinical trial is conducted

India, 

References & Publications (1)

Bhandari N, Sharma P, Glass RI, Ray P, Greenberg H, Taneja S, Saksena M, Rao CD, Gentsch JR, Parashar U, Maldonado Y, Ward RL, Bhan MK. Safety and immunogenicity of two live attenuated human rotavirus vaccine candidates, 116E and I321, in infants: results of a randomised controlled trial. Vaccine. 2006 Jul 26;24(31-32):5817-23. Epub 2006 May 12. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	- Safety		4 weeks after test article administration	Yes
Secondary	- 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.		4 weeks post administration of test article	No