Dose Escalation Study to Evaluate Oral Rotavirus Vaccine 116E Live Attenuated in Healthy Infants 8 to 20 Weeks Old
Condition: Diarrhea
MeSH terms: Diarrhea
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This study will be a Phase I, randomized, double blind, safety and immunogenicity trial of
      the Vero cell based 116E neonatal rotavirus vaccine candidate strain in healthy
      non-malnourished infants aged 8-20 weeks at three different dosage levels i.e.10^4.0, 10^5.0
      and 10^6.0 FFU and for three administrations of each of these dosages given to infants at
      4-week intervals. 180 infants (90 vaccinees/90 placebo) will be enrolled for each of the
      three dosage levels. The progression from the lower to the next higher dosage will be based
      on approval by the Data Safety Monitoring Board (DSMB) to be constituted by the Department of
      Biotechnology, New Delhi.
    

Detailed description: 
      Infants will be identified through a community survey in urban neighborhoods in the city of
      Delhi, India and screened at 6 weeks of age if parental consent is available. They will be
      given the first dose of EPI vaccines at this age. Of those screened, eligible infants will be
      given the first administration of the test vaccine/placebo at 8 weeks of age if they meet the
      enrollment inclusion criteria, and consent is available. The safety profile will be studied
      through daily home visits for 14 days post administration. Stool specimens will be collected
      before vaccination (day 0) and on days 3, 7 and 28 post administration of vaccine/placebo.
      Subsequently, two contacts will be made; a home visit on day 21 and a clinic visit on day 28.
      On the day 28 visit, a stool and blood specimen will be collected. Prior to each
      administration of vaccine/placebo the infants will be assessed for any contraindications.

      All screened infants will be offered EPI vaccines as scheduled. The second and third
      administration of study vaccine/placebo will be at 12 and 16 weeks of age and the same
      strategy will be followed for each of the three dosages The study vaccine/placebo are not
      being administered with the EPI vaccines even though in the future rotavirus vaccine and the
      EPI vaccines may be coadministered. For the purpose of this study this schedule is being
      adopted, as no data are available on the interaction of EPI vaccines with this rotavirus
      vaccine candidate.

      Baseline sera will be collected at 6 weeks (at the time of screening) and again 4 weeks after
      administration of the vaccine/placebo in a randomly selected subsample after the first (60
      infants), second (60 infants) and third (60 infants) administration of each dosage.

      Clinical adverse events will be monitored and relatedness to vaccine/placebo administration
      assessed for 14 days after each administration of the dosage under study, whereas monitoring
      for symptoms of intussusception will be assessed throughout the 28 day follow up period.
      Laboratory adverse events will be monitored for upto 28 days after first administration of
      each dosage. After the 4 week follow up of the third administration of the vaccine/placebo of
      the lowest dosage (10^4.0) is completed for all enrolled infants and the data safety
      monitoring board (DSMB) meeting will be convened and the data from the study will be
      analyzed, the code broken. If the DSMB declares the dosage safe, guided by the apriori
      criteria, the team will move on to screening infants for the next higher dosage (10^5.0) and
      the strategy listed above will be repeated for a total of 180 enrolled infants (90
      vaccinees/90 placebo). The DSMB will again meet to review the data available from this cohort
      (i.e. 10^5.0) and the team will proceed to screen infants for the next higher dosage (10^6.0)
      only if the former is declared safe.

      At the end of the study i.e. after the last visit of the last participant, based on
      reactogenicity and immunogenicity profile of each dosage, the appropriate dosage will be
      selected for further clinical evaluation.
    

Intervention name(s): Oral Rotavirus Vaccine 116E Live Attenuated
Intervention type(s): Biological
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomised double blind placebo controlled tri
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Rotavirus, diarrhea, vaccine