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

NCT ID: NCT00280111

Last Updated: 2008-07-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-01-31
• Study Completion Date: 2005-05-31

Brief 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.

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.

Conditions

Rotavirus Infections

Keywords

rotavirus; vaccine; safety; immunogenicity; infants

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

1

116E AGMK

Group Type: EXPERIMENTAL

116E AGMK

Intervention Type: BIOLOGICAL

Single dose of 116E 10\^5 FFu

2

I321 AGMK

Group Type: EXPERIMENTAL

I321

Intervention Type: DRUG

Single dose of I321 10\^5 FFu

3

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

1 crystal of potassium permanganate dissolved in the bicarbonate buffer to colour match the vaccine

Interventions

116E AGMK

Single dose of 116E 10\^5 FFu

Intervention Type: BIOLOGICAL

I321

Single dose of I321 10\^5 FFu

Intervention Type: DRUG

Placebo

1 crystal of potassium permanganate dissolved in the bicarbonate buffer to colour match the vaccine

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Healthy infants
• Consent available

Exclusion Criteria

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

• Minimum Eligible Age: 8 Weeks
• Maximum Eligible Age: 12 Weeks
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

All India Institute of Medical Sciences

OTHER

Sponsor Role: collaborator

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

Centers for Disease Control and Prevention

FED

Sponsor Role: collaborator

Stanford University

OTHER

Sponsor Role: collaborator

Indian Institute of Science

OTHER_GOV

Sponsor Role: collaborator

Children's Hospital Medical Center, Cincinnati

OTHER

Sponsor Role: collaborator

Ministry of Science and Technology, India

OTHER_GOV

Sponsor Role: collaborator

PATH

OTHER

Sponsor Role: collaborator

Society for Applied Studies

OTHER

Sponsor Role: lead

Responsible Party

All India Institute of Medical Sciences

Principal Investigators

Maharaj K Bhan, MD

Role: PRINCIPAL_INVESTIGATOR

All India Institute of Medical Sciences

Pratima Ray, PhD

Role: PRINCIPAL_INVESTIGATOR

All India Institute of Medical Sciences

Locations

Society for Applied Studies

New Delhi, National Capital Territory of Delhi, India

Countries

India

References

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. doi: 10.1016/j.vaccine.2006.05.001. Epub 2006 May 12.

Reference Type: BACKGROUND

PMID: 16735085 (View on PubMed)

Other Identifiers

U01AI053719-02

Identifier Type: NIH

Identifier Source: secondary_id

View Link

03-153

Identifier Type: -

Identifier Source: org_study_id