New trivalent and combined type 1 & 2 oral polio vaccines

A Phase 1/2, Randomized, Observer-Blind, Active-Controlled, Age De-escalation, Dose Combination Ranging Study to Assess the Safety and Immunogenicity of Co-administered Novel Live Attenuated Trivalent Oral Poliomyelitis Vaccine in Healthy Adults, Young Children, and Neonates and Co-administered Novel Live Attenuated Monovalent Oral Poliomyelitis Vaccines 1 and 2 in Neonates in Bangladesh

This tests whether new trivalent and combined type 1+2 oral polio vaccines are safe and produce protective antibody responses in healthy adults, young children, and newborns.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 2400 (estimated)
• Ages: 0 Days to 45 Years
• Sex: All
• Sponsor: Path (Academic / other)
• Locations: 2 sites (Dhaka and 1 other locations)
• Trial ID: NCT06137664 on ClinicalTrials.gov

What this trial studies

The trial co-administers novel monovalent oral poliovirus vaccines (types 1, 2, and 3) to simulate a trivalent vaccine and compares outcomes to an active bOPV (types 1 and 3) control. Enrollment is age-descending and staggered, starting with adults, then young children, and finally neonates, with dose-escalation and Protocol Safety Review Team (PSRT) reviews after early safety data. Participants are randomized into multiple groups to compare safety, tolerability, and immunogenicity, with neonatal cohorts receiving four vaccinations to measure cumulative seroconversion of poliovirus neutralizing antibodies. The single-center study is conducted at ICDDR,B in Dhaka and uses predefined safety triggers and comparisons across tnOPV combinations and combined nOPV1+nOPV2 regimens.

Who should consider this trial

Good fit: Ideal candidates are healthy adults (18–45) and young children (1 to <5) who completed routine polio immunizations, and healthy neonates (within 3 days of birth) who have not yet received polio vaccine.

Not a fit: Patients with significant medical conditions, immunodeficiency, pregnancy or breastfeeding, or who do not meet the age, health, or residency criteria are unlikely to qualify or receive benefit from this protocol.

Why it matters

Potential benefit: If successful, these vaccines could provide broader and potentially safer oral polio protection for newborns and children and help reduce polio transmission.

How similar studies have performed: Monovalent nOPV2 has been deployed under emergency use with promising safety and immunogenicity data, but simulating a trivalent novel OPV by co-administering monovalents and testing combined nOPV1+nOPV2 is a more recent, less extensively tested approach.

Eligibility criteria

Inclusion Criteria

Inclusion Criteria for all participants:

1. Healthy, as defined by the absence of any clinically significant medical condition or congenital anomaly as determined by medical history, physical examination, and clinical assessment of the investigator.
2. Participant or parent of the participant is willing and able to provide written informed consent prior to performance of any study-specific procedure.
3. Resides and plans to remain in study area and participants and parent, when applicable, understands and is able and willing to adhere to all study visits and procedures (as evidenced by a signed informed consent form \[ICF\] and assessment by the investigator).

   Inclusion Criteria for Cohort 1 participants only:
4. Males or females, from 18 to 45 years of age (inclusive) at the time of enrollment.
5. If female and of childbearing potential\*, not breastfeeding and not pregnant (based on a negative urine pregnancy test at screening and a negative urine pregnancy test during the 24 hours prior to any study vaccination \[if screening occurs within 24 hours prior to vaccination, a single negative pregnancy test is acceptable\]), agreeing to not become pregnant through other means (e.g., artificial insemination and IVF) and have repeated pregnancy tests prior to any study vaccination, and having practiced adequate contraception\*\* for 30 days prior to first study vaccination and willing to continue using adequate contraception consistently for at least 90 days after the last study vaccination.
6. Born and raised in Bangladesh in 1990 or later; if born before 1990 or not born and raised in Bangladesh, has documentation of a complete poliomyelitis immunization series containing OPV or IPV.

   Inclusion Criteria for Cohort 2 participants only:
7. Male or female child from 1 to less than 5 years of age at the time of enrollment (from the first birthday up to the day prior to the fifth birthday).
8. Based on documentation, previously received a 3 or 4 dose primary poliomyelitis immunization series containing bOPV ± IPV, with last dose received more than 3 months prior to initial study vaccination.

   Inclusion Criteria for Cohort 3 participants only:
9. Male or female newborn neonate (day of birth+ 3-day window), at the time of initial study vaccination.
10. Prior to study vaccination has received no doses of IPV or OPV or rotavirus vaccine, based upon documentation or parental history.
11. Agreement to receive polio EPI vaccines under a modified schedule.

Exclusion Criteria

Exclusion Criteria for all participants (unless otherwise specified):

1. Presence of anyone under 10 years of age in the participant's household (living in the same house or apartment unit) who does not have complete "age appropriate" vaccination status with respect to poliovirus vaccines based on the vaccination records at the time of study vaccine administration. For household members younger than 10 years of age-appropriate vaccination is a complete series of at least three doses of OPV.
2. A known allergy, hypersensitivity, or intolerance to any components of the study vaccines, including all macrolide and aminoglycoside antibiotics (e.g., erythromycin and kanamycin).
3. Any self-reported known or suspected immunosuppressive or immunodeficiency condition (including HIV infection) in the participant or household member (living under the same roof/in the same building rather than in the same compound).
4. Receipt of any immune-modifying or immunosuppressant drugs within 6 months prior to the first study vaccine dose or planned use during the study.
5. Any known or suspected bleeding disorder in the participant that would pose a risk to venipuncture or intramuscular injection.
6. Moderate or severe (grade ≥ 2) acute illness including vomiting, diarrhea at the time of enrollment/first study vaccination - temporary exclusion.
7. Presence of fever within the 72 hours of the day of enrollment/first study vaccination (oral temperature ≥38.0˚C for Cohort 1; axillary temperature ≥37.5˚C for Cohorts 2 and 3) or any antipyretic use within past 24 hours - temporary exclusion for Cohorts 1 and 2.
8. Evidence of a clinically significant major congenital or genetic defect as judged by the investigator.
9. History of chronic administration (defined as more than 14 days) of immunosuppressant medications, including corticosteroids (\> 0.5mg/kg/day or 20 mg/day of prednisolone (or equivalent) within 6 months prior to first study vaccine dose. Topical and inhaler steroids are permitted (unless indicative of a significant chronic illness otherwise excluding the young child).
10. Participation in another investigational product (drug or vaccine, including prior polio vaccine trials) clinical trial within 30 days prior to entry in this study or receipt of any such investigational product other than the study vaccine within 30 days prior to the first administration of study vaccine, or planned participation in another investigational product clinical trial during the study period.
11. Receipt of transfusion of any blood product or immunoglobulins within 12 months prior to the first administration of study vaccine or planned during the study period.
12. Participant or parent, when applicable, has any condition that in the opinion of the investigator would increase the participant's health risks in study participation or would increase the risk of not achieving the study's objectives (e.g., would compromise adherence to protocol requirements or interfere with planned safety and immunogenicity assessments).

    Exclusion Criteria for Cohort 1 participants:
13. Receipt of polio vaccine within 12 months before the start of the study.
14. Having Crohn's disease or ulcerative colitis or having had major surgery of the gastrointestinal tract involving significant loss or resection of the bowel.
15. Will have household direct or close professional contact during the study with pregnant women.
16. Will have household direct or close professional (e.g., neonatal nurses) contact during the study with children less than 2 years of age or with individuals who are encopretic (i.e., soiling of underwear with stool by children who are past the age of toilet training or other individuals, including adults, with fecal incontinence).
17. Will have professional handling of food, catering, or food production activities during the study.

    Exclusion Criteria for Cohort 2 participants:
18. Any participating children attending day care or pre-school during their participation in the study until one month after their last study vaccine administration.
19. Presence of severe malnutrition \[weight-for-length/height z-score \<-3SD median (per WHO published child growth standards)\]-temporary exclusion if marginal and subsequently gains weight.

    Exclusion Criteria for Cohort 3 participants:
20. Low birth weight (LBW) in newborn participants which is defined as a birth weight of less than 2500 g (up to and including 2499 g) at the time of birth or by the time of enrollment
21. Premature birth (less than 37 weeks gestation).
22. From multiple birth (due to increased risk of OPV transmissions between siblings).

Where this trial is running

Dhaka and 1 other locations

• International Centre for Diarrhoeal Disease Research — Dhaka, Bangladesh (Not_yet_recruiting)
• International Centre for Diarrhoeal Disease Research — Dhaka, Bangladesh (Recruiting)

Study contacts

• Study coordinator: Nicole Grunenberg, MD

Conditions Poliomyelitis; poliovirus vaccine; Trivalent oral poliovirus vaccine; Novel oral poliovirus vaccine