Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomized, Double-blind, Placebo-controlled Phase III Clinical Trial to Assess the Efficacy and Safety of a Pentavalent Rotavirus Vaccine (BRV-PV) Against Severe Rotavirus Gastroenteritis Among Infants in Niger
Brief Summary: The study is a double-blinded, randomized, placebo-controlled, trial with two groups of infants receiving vaccine or placebo to assess the efficacy and safety of BRV-PV. Three doses of BRV-PV containing ≥ Log10 5.6 FFU/Dose of each serotype G1, G2, G3, G4 and G9 will be administered at 4 week intervals between doses. The first administration will occur at 6-8 weeks of age.

We hypothesize a difference in vaccine efficacy of three doses of BRV-PV vaccine vs. placebo against severe rotavirus gastroenteritis in healthy infants in Niger.

Active surveillance for gastroenteritis episodes will be conducted throughout the trial. Surveillance for adverse events will be carried out among all children from the time of first vaccination and 28 days post-Dose 3. Surveillance for all serious adverse events, including intussusception and death, will be conducted on all participants until they each reach two years of age.

To assess the effect of prenatal nutrition supplementation on infant immune response to the BRV-PV vaccine, study villages in the immunogenicity sub-cohort will be randomized in a 1:1:1 ratio to provide pregnant women with daily iron-folate, multiple micronutrients or a lipid-based nutrition supplement. Infants of participating women, if eligible at 6-8 weeks of age, will be randomized in a 1:1 ratio to receive three doses of vaccine or placebo and enter the main trial as part of the immunogenicity sub-cohort.


Options:
A: Inclusion Criteria:

* At dose 1

  1. A healthy male or female, 6 to 12 weeks of age (42 days to 84 days of age).
  2. Full term gestation (\>=37 weeks).
  3. Birth weight of the subject should be \>=2.5 kg.
  4. Healthy subjects as established by medical history and clinical examination before entering into the study.
  5. Did not use any dose of Rota virus vaccine.
  6. Written informed consent obtained from the parent or guardian of the subject.
* At dose 2

  1. Received dose 1.
  2. Oral informed consent obtained from the parent or guardian of the subject for continuing participate the study.
* At dose 3

  1. Received both dose 1 and dose 2.
  2. Oral informed consent obtained from the parent or guardian of the subject for continuing participate the study.

Exclusion Criteria:

* At dose 1

  1. Has a chronic disease (cardiovascular, liver, kidney disease).
  2. Acute disease at the time of enrolment.
  3. Administering corticosteroids (\> 1mg/kg/day).
  4. Received any immunosuppressive therapy within 4 week before vaccination (Administration of immunoglobulins and/or any blood product or corticosteroids for \>2 weeks).
  5. Immunosuppressive or immunodeficient condition.
  6. Family has immunosuppressive or immunodeficient condition medical history.
  7. History of high fever convulsion.
  8. Allergic or reaction with any component of vaccine, includes anaphylactic shock with any antibiotic.
  9. Preterm of gestation delivery (gestation period \< 37 weeks).
  10. Low birth weight (\<2.5 kg).
  11. Fever (axillary temperature \>38oC) within 3 days before or on the day of vaccination.
  12. Malnutrition.
  13. Has any type of blood disorder, leukemia, or malignant tumor which can affect the bone marrow or lymph system.
  14. Use of any investigational or non-registered product (unlicensed drug or vaccine) other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period.
* At dose 2

  1. Acute disease at the time of 2nd dose.
  2. Administering corticosteroids (\> 1mg/kg/day).
  3. Received any immunosuppressive therapy within 4 week before vaccination (Administration of immunoglobulins and/or any blood product or corticosteroids for \>2 weeks).
  4. History of allergic disease or reactions likely to be exacerbated by any component of the study vaccine.
  5. Fever (axillary temperature \>38oC) within 3 days before or on the day of vaccination.
  6. Has any type of blood disorder, leukemia, or malignant tumor which can affect the bone marrow or lymph system.
  7. Use of any investigational or non-registered product (unlicensed drug or vaccine) other than the study vaccine during the study period.
* At dose 3

  1. Acute disease at the time of 3rd dose.
  2. Administering corticosteroids (\> 1mg/kg/day).
  3. Received any immunosuppressive therapy within 4 week before vaccination (Administration of immunoglobulins and/or any blood product or corticosteroids for \>2 weeks).
  4. History of allergic disease or reactions likely to be exacerbated by any component of the study vaccine.
  5. Fever (axillary temperature \>38oC) within 3 days before or on the day of vaccination.
  6. Has any type of blood disorder, leukemia, or malignant tumor which can affect the bone marrow or lymph system.
  7. Use of any investigational or non-registered product (unlicensed drug or vaccine) other than the study vaccine during the study period.
B: Inclusion Criteria:

* Aged ≥ 42 days and ≤ 89 days on the day of inclusion
* Born at full term of pregnancy (≥ 36 weeks)
* Informed consent form signed by the parent(s) or other legally authorized representative(s) before the 1st study related procedure
* Vaccination with a hepatitis B vaccine at least 30 days before inclusion
* Able to attend all scheduled visits and to comply with all trial procedures(i.e., access to a phone)
* Provide blood sample prior to Dose 1
* Parent or legal representative willing to take rectal temperatures after each vaccination.

Exclusion Criteria:

* Participation in another clinical trial in the 4 weeks preceding the (first)trial vaccination
* Planned participation in another clinical trial during the present trial period
* Personal or immediate family history of congenital or acquired immunodeficiency, immunosuppressive therapy such as long-term systemic corticosteroids therapy
* Known or suspected systemic hypersensitivity to any of the vaccine components or history of a life-threatening reaction to a vaccine containing the same substances as the trial vaccine(s)
* Chronic illness that could interfere with trial conduct or completion
* Received blood or blood-derived products since birth
* Any vaccination in the 2 weeks preceding the first trial vaccination or planned in the 4 weeks after any trial vaccination. Flu vaccine could be administered only 2 weeks after any trial vaccination
* Previous vaccination with any acellular pertussis- (DTaP) or whole cell pertussis- (DTwP) based combination vaccines, Haemophilus influenzae type b (Hib)-conjugate, poliovirus, or pneumococcal conjugate vaccines
* Coagulation disorder contraindicating intramuscular (IM) vaccination
* Clinically significant findings on review of systems (determined by investigator or sub-investigator to be sufficient for exclusion)
* Developmental delay or neurological disorder
* Any condition which, in the opinion of the investigator, would interfere with the evaluation of the vaccine or pose a health risk to the subject.
C: Inclusion Criteria:

* Parent or legal guardian agrees to have infant participate by giving written informed consent

Exclusion Criteria:

* History of congenital abdominal disorders, prior rotavirus gastroenteritis, chronic diarrhea, failure to thrive, or abdominal surgery
* History of intussusception
* Known or suspected impairment of immunological function, including Severe

Combined Immunodeficiency (SCID)

* Prior administration of any rotavirus vaccine
* Clinical evidence of active gastrointestinal illness, with the exception of well-controlled gastroesophageal reflux disease (GERD)
* Receipt of 1) systemic corticosteroids (≥ 2mg/kg total daily dose of prednisone or equivalent) for 14 consecutive days or more since birth, or 2) systemic corticosteroids ≥ 2mg/kg/dose within 7 days prior to the administration of the first dose of study vaccine. Participant using non-systemic corticosteroids will be eligible for vaccination.
* Residing in a household with an immunocompromised person
* Prior receipt of a blood transfusion or blood products, including immunoglobulins
* Participation in another interventional study within 14 days prior to the first study vaccination or expected anytime during the study
* Receipt of investigational inactivated vaccines within 14 days or investigational live vaccines within 28 days prior to the first study vaccination or expected anytime during the study
D: Inclusion Criteria:

1. aged 6-8 weeks at the time of inclusion
2. able to swallow and no history of vomiting within 24 hours
3. resident in Madarounfa Health District and within the catchment area of the central health facility
4. intending to remain in the study area for 2 years
5. parent/guardian providing written informed consent

Exclusion Criteria:

Any of the following will exclude an infant from randomization in the study:

1. known history of congenital abdominal disorders, intussusception, or abdominal surgery
2. receipt of intramuscular, oral, or intravenous corticosteroid treatment within 2 wks
3. receipt or planned administration of a blood transfusion or blood products, including immunoglobulins
4. any known immunodeficiency condition
5. any serious medical condition
6. any other condition in which, in the judgment of the investigator, would interfere with or serves as a contraindication to protocol adherence or the parent/guardian's ability to give informed consent

Answer: D