clinical trial on the oral hexavalent reassortant rotavirus attenuated live vaccine (vero cells)

Conditions: Rotavirus Gastroenteritis

Summary: the phase i clinical trial of the oral hexavalent reassortant rotavirus attenuated live vaccine (vero cells) will be conducted in a population ranging from 6 weeks to 59 years of age. the objective of this study is to evaluate the safety of investigational vaccine in healthy adults and children, as well as its safety tolerability, and immunogenicity in healthy infants. the study will be an open-label observation in adults and children, and a randomized, double-blind, placebo-controlled clinical trial in infants.

the phase i clinical trial is an open-label observation involving healthy adults and children, as well as a randomized, double-blind, placebo-controlled study in healthy infants to evaluate the safety, tolerability, and immunogenicity of the investigaional vaccine. the investigational vaccine is available in both high-dose and low-dose formulations. the placebo is identical to the trial vaccine in all components except for the rotavirus. this study will enroll 100 participants, consisting of 20 adults aged 18-59 years, 20 children aged 2-6 years, and 60 infants aged 6-12 weeks. participants will be enrolled sequentially, starting with adults, followed by children, and then infants. enrollment for the subsequent group will begin after a 14-day safety observation period and confirmation of acceptable safety in the preceding group. adult and child participants will receive the investigational vaccine in an open-label manner. the infants will be enrolled into two cohorts of 30 participants each: a low-dose cohort and a high-dose cohort. within each cohort, the infants will be randomly assigned to two groups at a ratio of 2:1 and will receive either the investigational vaccine or a placebo in a double-blind manner. the immunization schedule for both the vaccine and placebo consists of three doses administered at 28-day intervals. adverse events (ae) will be collected for all participants until 42 days after the last dose vaccination. stool samples will be collected after each vaccination to detect vaccine strain shedding among infant participants. serious adverse events (sae) will be observed for 6 months from the last dose for adults and children or 12 months for infants. blood samples from the infants will be collected at predetermined times to evaluate the immunogenicity of the investigational vaccine.

Eligibility criteria:
inclusion criteria: 1. the participant and/or their guardian is willing and able to comply with all study procedures, sign the informed consent form, and remain contactable throughout the study period. 2. provide legal identification. 3. male or female, aged 6 to 12 weeks, or 2 to 6 years, or 18 to 59 years, and in good health. 4. fertile participants have no plans for pregnancy from the time of signing the informed consent form until 3 months after the last dose of the study vaccine and agree to use effective contraception, and have no plans for sperm or egg donation. exclusion criteria: 1. known allergy to the vaccine or its components, such as urticaria, dyspnea, angioedema, etc. 2. current diarrhea or vomiting, or other gastrointestinal diseases, or having experienced gastroenteritis or any acute illness or acute exacerbation of chronic disease within the past 7 days, or those currently using antibiotics or antiviral therapy. 3. history of intussusception or chronic gastrointestinal disease, including gastrointestinal congenital anomalies that can easily cause intussusception (e.g., meckel's diverticulum). 4. for infant and pediatric participants: congenital malformations or developmental disabilities, genetic defect diseases, severe malnutrition, or severe chronic diseases (such as down syndrome, diabetes, sickle cell anemia, neurological disorders, guillain-barré syndrome); for adult participants: uncontrolled chronic diseases or severe disease history, including but not limited to cardiovascular diseases (such as drug-uncontrolled hypertension, i.e., systolic blood pressure ≥140 mmhg or diastolic blood pressure ≥90 mmhg), hematologic diseases, hepatic and renal diseases, gastrointestinal diseases, respiratory diseases, malignant tumors, history of major organ transplantation, or any other disease or medical condition that the investigator believes may interfere with the trial results. 5. presence of autoimmune diseases or immunodeficiency diseases (including but not limited to systemic lupus erythematosus, ankylosing spondylitis, autoimmune thyroid disease, asplenia, functional asplenia, hiv infection). 6. household members living with the participant are in an immunodeficient or immunosuppressed state or are currently/soon to be receiving immunosuppressive therapy, cytotoxic therapy, etc. 7. presence of coagulation dysfunction (such as deficiency of coagulation factors, abnormal platelets). 8. received \>14 days of immunosuppressive therapy or other immunomodulatory therapy, cytotoxic therapy within the past 6 months (for adult and pediatric participants) or since birth (for infant participants), or planned to receive such treatment during the study period. 9. chronic alcoholism \[weekly alcohol consumption \>14 drinking units (1 drinking unit = 14 grams of 100% alcohol = 360 ml beer, or 150 ml wine, or 45 ml distilled spirits/liquor)\] or history of drug abuse (repeated, excessive use of narcotic drugs, psychotropic substances, volatile organic solvents, etc.) (for adult participants). 10. suffering from/having suffered from severe neurological diseases (epilepsy, convulsions or seizures) or mental illness, or having a family history of the same. 11. received immunoglobulin or other blood products within 6 months before receiving the trial vaccine (for adult and pediatric groups) or in the past (for infant group), or planned to receive such treatment during the study period. 12. received other investigational drugs or vaccines within the past 30 days, or planned to receive such drugs or vaccines during the study period. 13. received live attenuated vaccines or covid-19 vaccines within the past 14 days, or subunit or inactivated vaccines and other process vaccines within the past 7 days. 14. had axillary temperature ≥38.0℃ within the past 3 days. 15. on the day planned for vaccination with the trial vaccine, having a fever with axillary temperature \>37.0℃. 16. clinical laboratory tests showing laboratory abnormalities beyond the reference range that are clinically significant (for adult and pediatric groups): * hematology test indicators: white blood cell count, hemoglobin, platelet count. * biochemical blood test indicators: alanine aminotransferase (alt), aspartate aminotransferase (ast), total bilirubin (tbil), creatinine (cr), fasting blood glucose (glu). * urinalysis test indicators: urine protein (pro). 17. fertile women with positive urine pregnancy test or breastfeeding. 18. currently or planning to participate in other vaccine or drug clinical trials. 19. any other factors that the investigator deems unsuitable for participation in the clinical trial. additional exclusion criteria for infants aged 6 to 12 weeks 1. previously received rotavirus vaccine. 2. history of rotavirus infection. 3. neonatal gestational age \<37 weeks or ≥42 weeks. 4. birth weight \<2500g. 5. history of difficult labor, resuscitation from asphyxia, or neurological damage at birth.

Keywords: phase i sequential design safety tolerability immunogenicity rotavirus gastroenteritis vaccine