Prior to study initiation, study clinics and offices will be set up in each of the enrollment
sites. Awareness about the study will be created in the community. All categories of staff
will be recruited and trained. CRFs, SOPs and registers will be developed. Regulatory and IRB
approvals will be obtained. Permissions and clearances will be sought from the Government.
The study team will identify pregnant women, newborns and infants aged less than 8 weeks as
potential participants. Information about the study will be shared with these families, and
those willing to participate will be enrolled after obtaining consent and subsequent
screening of the subject. Subjects will be enrolled in the study since 2 months + 29 days of
age and will be given 3 doses of the Test Article/placebo along with childhood vaccines
(which will include vaccines against diphtheria, pertussis, tetanus, Haemophilus influenzae
B, Hepatitis B and IPV, and pneumococcal conjugated vaccine at 2 and 4 month of age).
Participants vaccinated with a dose of vaccine from the National Immunization Program
corresponding to their current age, in which more than 48 hours have passed since the last
dose received, the subject will not be considered for the study. The Test Article will be
liquid ORV 116E, 105.0ffu stored at 2-8°C. The Test Article/placebo will be co-administered
with the childhood vaccines that are scheduled at the regular National Program of
Immunization vaccination visits around 2 months, 4 months and 6 months of age. After each
visit, a safety evaluation will be carried out on all participants. A card will be given to
the caregivers for the daily record of temperature, diarrhea, vomiting, food refusal and/or
irritability, for a period of 1 week. On day 3 and 7, the research team will contact the
caregivers by telephone to note the general state of health of the infant and to collect the
card. The subjects will be followed f or episodes of acute gastroenteritis every two weeks
through contact by email or text message (+ 2 days), until 8 months + up to 14 days post 3
doses of vaccination. The expected duration of subjec participation is 13 months. In addition
to the contacts at every two weeks follow-up, parents/primary caregiver will be advised to
contact the study team whenever the subject has symptoms of gastroenteritis (GE; the
operational definition of GE for this study will be the change in the habitual pattern of the
stools, both in more frequent passage than is normal for the individual and/or in the
decrease in stool consistency), signs or symptoms of suspected intussusception (IS, defined
as stomach pain and vomiting that start suddenly and come and go several times per hour, and
then later, bloody stools) or any other illness requiring hospital referral. If the caregiver
report symptoms of GE, an "illness visit" will be activated. The caregiver will be asked to
collect a stool specimen. The field worker will ensure that the parents/primary caregiver
have stool containers available with them so that stool specimens can be collected whenever
the enrolled subject has GE. In the next 24-48 hours, the stool sample will be processed with
an ELISA rotavirus test. If the result is negative, the illness visit will be discontinued,
and the episode will be registered. If the result is positive, a daily telephone follow-up
will be carried out throughout the GE episode, up to 24 hours after the last altered stool.
If during the illness visit any symptom/sign of dehydration and/or clinical severity is
verified by the research team, the participant will be invited to be evaluated at the study
center. During the illness visit the following variables will be collected daily by the
caregiver in an illness visit card: stools number and consistency, vomiting episodes,
temperature (based on subjective perception of the caregiver of potential fever, or at the
same time point during the consecutive days, preferably between 2 and 8 PM), administration
of ORS yes/no, number of administrations, and if possible, volume administered). If the child
is hospitalized, the following information will be obtained from hospitalization charts:
number and consistency of stool episodes, number of vomiting episodes, highest daily
temperature, hydration evaluation, use of ORS and/or IV solutions (volume used and fluid
description) duration of hospitalization, and any potential complication. If in the follow-up
every two weeks of the participants, an episode that did not activate the illness visit of GE
is reported or detected, the episode will be recorded and an attemp t will be made to collect
as much data as possible retrospectively.
The study team will contact the parents/primary caregiver through mobile phone and collect
the information of the illness visit card.
Out of the enrolled subjects, 150 from each group will constitute the "Immunogenicity
Subset".
Visit 1 Baseline (vaccine at 2 Months of age + 29 days):
The participant will be screened for eligibility based on vitals (heart rate and body
temperature) and physical examination.
If the participant is eligible (in good general health or stable preexisting disease as
per the discretion of the Principal investigator).
A study vaccine/placebo will be administered. Following vaccination, participants will
remain at the study site for at least 30minutes of observation to record any immediate
adverse event.
Daily card will be given to the parent/primary caregiver.
Blood sample (3 mL) will be collected for immunogenicity analysis in a subset of (n=300)
participants prior to vaccination.
Visit 2 (vaccine at 4 Months of age, +29 days):
Study participants will return to the OPD for vitals and physical examination (general
and systemic examination). A study vaccine
/placebo will be administered.
Following vaccination, participants will remain at the study site for at least 30minutes
of observation to record any adverse event.
Daily card will be collected and a new card will be given to the parent/primary
caregiver.
Visit 3 (vaccine at approximately 6 Months of age, +29 days):
Study participants will return to the OPD for vitals and physical examination (general
and systemic examination). A study vaccine
/placebo will be administered.
Following vaccination, participants will remain at the study site for at least 30minutes
of observation to record any adverse event.
Diary card will be collected and a new card will be given to the parent/primary
caregiver. Visit 4 (1 Month after visit 3 ++5days): (only for immunogenicity group)
Study participants (Subset) will return to the OPD for physical examination (general and
systemic examination) and diary card will be collected.
Blood sample (3 mL) will be collected for immunogenicity analysis in a subset of n=300.
Diary card (Photograph) will be collected from the non-immunogenic participants. Blood
samples: In the "Immunogenicity Subset", 3 ml blood specimens will be collected at
baseline and 28 (+) 5 days after the third dose of the Test Article/placebo to assess
the anti-rotavirus IgA antibody titer. Stool Specimens: The study team will attempt to
collect a stool specimen for every GE episode, preferably within the first 2 days after
episode onset . The stool specimen may be collected up to 7 days after the last day of
diarrhea. The stool specimens will be sent to the laboratory. If the episode is a
suspected intussusception or vaccine associated gastroenteritis that has occurred within
four weeks after each dose of the Test Article/placebo, the specimen will be sent to the
laboratory immediately for rotavirus testing and typing. For all ELISA RV positive
samples, an aliquot of the stool specimen will be assessed for 22 enteropathogens by
multiplex-PCR panel and to identify the genotype of the virus.