NCT05644184

Brief Summary

The purpose of this clinical trial is to assess the safety and tolerability (primary objective), immunogenicity (primary and secondary objectives), fecal shedding of vaccine viruses (secondary objective) and the potential for neurovirulence of shed virus (secondary objective) of a novel oral polio type 1 vaccine, nOPV1, as compared to Sabin monovalent type 1 vaccine controls (mOPV1), in healthy young children (192 subjects), infants (720 subjects), and neonates (1320 subjects).

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
2,232

participants targeted

Target at P75+ for phase_2

Timeline
0mo left

Started Mar 2023

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress99%
Mar 2023May 2026

First Submitted

Initial submission to the registry

November 10, 2022

Completed
29 days until next milestone

First Posted

Study publicly available on registry

December 9, 2022

Completed
4 months until next milestone

Study Start

First participant enrolled

March 27, 2023

Completed
3.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 15, 2026

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 15, 2026

Last Updated

January 9, 2026

Status Verified

January 1, 2026

Enrollment Period

3.1 years

First QC Date

November 10, 2022

Last Update Submit

January 7, 2026

Conditions

Keywords

Vaccine tolerabilityVaccine safetyVaccine reactogenicityVaccine viral sheddingVaccine immunogenicity

Outcome Measures

Primary Outcomes (4)

  • Frequency of serious adverse events (SAEs) from the time of first study vaccination through the end of the study

    Serious adverse event is any adverse event that results in any of the following outcomes: 1. Death 2. Is life-threatening (life-threatening means that the study participant was, in the opinion of the site PI or PATH, at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe). 3. Requires inpatient hospitalization or prolongation of existing hospitalization 4. Results in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions 5. Important medical event that may not result in one of the above outcomes but may jeopardize the health of the study participant and require medical or surgical intervention to prevent one of the outcomes listed in the above definition of serious adverse event

    From Day 1 to end of study, up to Day 197 (young children and neonates) or Day 225 (infants)

  • Frequency of solicited adverse events (AEs) for 7 days (day of vaccination and 6 following days) after each vaccination

    Solicited AEs are pre-specific AEs that are common or known to be associated with vaccination that are actively monitored as potential indicators of vaccine reactogenicity. The following specific solicited AEs will be monitored for this trial: * Fever (axillary temperature ≥ 37.5°C) * Vomiting * Diarrhea * Irritability * Decreased feeding or appetite * Fatigue or decreased activity

    From vaccination to 7 days post vaccination

  • Frequency of unsolicited AEs for 28 days (day of vaccination and 27 following days) after each vaccination

    Unsolicited AEs are any AEs reported spontaneously by the participant's parent, observed by the study personnel during study visits or identified during review of medical records or source documents. In the absence of a diagnosis, abnormal physical examination findings or abnormal clinical safety laboratory test results that are assessed by the investigator to be clinically significant will be reported as an AE.

    From vaccination to 28 days post vaccination

  • Post-vaccination frequency of seroconversion of type 1 anti-polio serum neutralizing antibody (NAb).

    Following two doses of nOPV1, at dose levels of 10\^6.5 and 10\^7.0 CCID50/dose, compared to mOPV1, in healthy neonates. For unvaccinated neonates, seroconversion will be defined as either a minimum 4-fold higher antibody titer relative to the expected level of maternal antibody and seropositivity (reciprocal titer ≥ 8) at the post-vaccination time point among those initially seropositive, or post-vaccination seropositivity among those initially seronegative.

    28 days post second vaccination

Secondary Outcomes (9)

  • Post-vaccination frequency of seroconversion of type 1 anti-polio serum NAb.

    Baseline and 28 days post vaccination (Day 1 and Day 29 for young children, Day 1, Day 29 and Day 57 for neonates and Day 29, Day 57 and Day 85 for infants)

  • Median type 1 anti-polio serum NAb titers.

    Baseline and 28 days post vaccination (Day 1 and Day 29 for young children, Day 1, Day 29 and Day 57 for neonates and Day 29, Day 57 and Day 85 for infants)

  • Type 1 anti-polio serum NAb Geometric Mean Titer (GMT).

    Baseline and 28 days post vaccination (Day 1 and Day 29 for young children, Day 1, Day 29 and Day 57 for neonates and Day 29, Day 57 and Day 85 for infants)

  • Post-vaccination GMT ratios of type 1 anti-polio serum NAb, adjusted for baseline immunity.

    Baseline and 28 days post vaccination (Day 1 and Day 29 for young children, Day 1, Day 29 and Day 57 for neonates and Day 29, Day 57 and Day 85 for infants)

  • Seroprotection rate, defined as type 1 anti-polio serum NAb reciprocal titer ≥ 8.

    Baseline and 28 days post vaccination (Day 1 and Day 29 for young children, Day 1, Day 29 and Day 57 for neonates and Day 29, Day 57 and Day 85 for infants)

  • +4 more secondary outcomes

Study Arms (15)

Group 1: Young Children, nOPV1 10^5.5 CCID50

EXPERIMENTAL

48 young children aged 1 to \<5 years will receive 2 doses of nOPV1 at a dose level of 10\^5.5 CCID50 on Day 1 and Day 29

Biological: Novel Live Attenuated Type 1 Oral Poliomyelitis Vaccine (nOPV1)

Group 3: Young Children, nOPV1 10^6.0 CCID50

EXPERIMENTAL

48 young children aged 1 to \<5 years will receive 2 doses of nOPV1 at a dose level of 10\^6.0 CCID50 on Day 1 and Day 29

Biological: Novel Live Attenuated Type 1 Oral Poliomyelitis Vaccine (nOPV1)

Group 5: Young Children, nOPV1 10^6.5 CCID50

EXPERIMENTAL

48 young children aged 1 to \<5 years will receive 2 doses of nOPV1 at a dose level of 10\^6.5 CCID50 on Day 1 and Day 29

Biological: Novel Live Attenuated Type 1 Oral Poliomyelitis Vaccine (nOPV1)

Groups 2, 4 and 6: Young Children, mOPV1

ACTIVE COMPARATOR

48 young children aged 1 to \<5 years will receive 2 doses of mOPV1 at a dose level of ≥ 10\^6.0 CCID50 on Day 1 and Day 29

Biological: Sabin Monovalent Oral Poliomyelitis Vaccine Type 1 (mOPV1)

Group 7: Infants, nOPV1 10^5.5 CCID50

EXPERIMENTAL

96 infants aged 6 weeks (+6 days) will receive 1 dose of IPV on Day 1, then 2 doses of nOPV1 at a dose level of 10\^5.5 CCID50 on Day 29 and Day 57, and a challenge dose of mOPV on Day 113.

Biological: Novel Live Attenuated Type 1 Oral Poliomyelitis Vaccine (nOPV1)Biological: Sabin Monovalent Oral Poliomyelitis Vaccine Type 1 (mOPV1)

Group 9: Infants, nOPV1 10^6.0 CCID50

EXPERIMENTAL

96 infants aged 6 weeks (+6 days) will receive 1 dose of IPV on Day 1, then 2 doses of nOPV1 at a dose level of 10\^6.0 CCID50 on Day 29 and Day 57, and a challenge dose of mOPV on Day 113.

Biological: Novel Live Attenuated Type 1 Oral Poliomyelitis Vaccine (nOPV1)Biological: Sabin Monovalent Oral Poliomyelitis Vaccine Type 1 (mOPV1)

Group 11: Infants, nOPV1 10^6.5 CCID50

EXPERIMENTAL

48 infants aged 6 weeks (+6 days) will receive 1 dose of IPV on Day 1, then 2 doses of nOPV1 at a dose level of 10\^6.5 CCID50 on Day 29 and Day 57, and a challenge dose of mOPV on Day 113.

Biological: Novel Live Attenuated Type 1 Oral Poliomyelitis Vaccine (nOPV1)Biological: Sabin Monovalent Oral Poliomyelitis Vaccine Type 1 (mOPV1)

Group 11b: Infants, nOPV1 10^6.5 CCID50

EXPERIMENTAL

96 infants aged 6 weeks (+6 days) will receive 1 dose of IPV on Day 1, then 3 doses of nOPV1 at a dose level of 10\^6.5 CCID50 on Day 29, Day 57 and Day 85, and a challenge dose of mOPV on Day 141.

Biological: Novel Live Attenuated Type 1 Oral Poliomyelitis Vaccine (nOPV1)Biological: Sabin Monovalent Oral Poliomyelitis Vaccine Type 1 (mOPV1)

Group 13: Infants, nOPV1 10^7.0 CCID50

EXPERIMENTAL

96 infants aged 6 weeks (+6 days) will receive 1 dose of IPV on Day 1, then 3 doses of nOPV1 at a dose level of 10\^7.0 CCID50 on Day 29, Day 57 and Day 85, and a challenge dose of mOPV on Day 141.

Biological: Novel Live Attenuated Type 1 Oral Poliomyelitis Vaccine (nOPV1)Biological: Sabin Monovalent Oral Poliomyelitis Vaccine Type 1 (mOPV1)

Group 15: Infants, nOPV1 10^7.5 CCID50

EXPERIMENTAL

96 infants aged 6 weeks (+6 days) will receive 1 dose of IPV on Day 1, then 3 doses of nOPV1 at a dose level of 10\^7.5 CCID50 on Day 29, Day 57 and Day 85, and a challenge dose of mOPV on Day 141.

Biological: Novel Live Attenuated Type 1 Oral Poliomyelitis Vaccine (nOPV1)Biological: Sabin Monovalent Oral Poliomyelitis Vaccine Type 1 (mOPV1)

Groups 8, 10, 12, 12b, 14, 16: Infants mOPV1

ACTIVE COMPARATOR

192 infants aged 6 weeks (+6 days) will receive 1 dose of IPV on Day 1 then 2 to 3 doses of mOPV1 at a dose level of ≥10\^6.0 CCID50 on Day 29, Day 57, Day 85 (groups 12b, 14 \& 16 only) and a challenge dose of mOPV on Day 113 (groups 8, 10 \& 12) on Day 141 (groups 12b, 14 \& 16)

Biological: Novel Live Attenuated Type 1 Oral Poliomyelitis Vaccine (nOPV1)Biological: Sabin Monovalent Oral Poliomyelitis Vaccine Type 1 (mOPV1)

Group 17: Neonates, nOPV1 10^6.5 CCID50

EXPERIMENTAL

330 neonates (day of birth +3 days) will receive 3 doses of nOPV1 at a dose level of 10\^6.5 CCID50 on Day 1, Day 29 \& Day 57

Biological: Novel Live Attenuated Type 1 Oral Poliomyelitis Vaccine (nOPV1)

Group 19: Neonates, nOPV1 10^7.0 CCID50

EXPERIMENTAL

330 neonates (day of birth +3 days) will receive 3 doses of nOPV1 at a dose level of 10\^7.0 CCID50 on Day 1, Day 29 \& Day 57

Biological: Novel Live Attenuated Type 1 Oral Poliomyelitis Vaccine (nOPV1)

Group 21: Neonates, nOPV1 10^7.5 CCID50

EXPERIMENTAL

330 neonates (day of birth +3 days) will receive 3 doses of nOPV1 at a dose level of 10\^7.5 CCID50 on Day 1, Day 29 \& Day 57

Biological: Novel Live Attenuated Type 1 Oral Poliomyelitis Vaccine (nOPV1)

Groups 18, 20 & 22: Neonates, mOPV1

ACTIVE COMPARATOR

330 neonates (day of birth +3 days) will receive 3 doses of mOPV1 at a dose level of ≥ 10\^6.0 CCID50 on Day 1, Day 29 \& Day 57

Biological: Sabin Monovalent Oral Poliomyelitis Vaccine Type 1 (mOPV1)

Interventions

The Sabin Monovalent Oral Poliomyelitis Vaccine Type 1 control and challenge vaccine (mOPV1) contains ≥ 10\^6.0 CCID50 per 0.1 mL (2 drops) dose.

Group 11: Infants, nOPV1 10^6.5 CCID50Group 11b: Infants, nOPV1 10^6.5 CCID50Group 13: Infants, nOPV1 10^7.0 CCID50Group 15: Infants, nOPV1 10^7.5 CCID50Group 7: Infants, nOPV1 10^5.5 CCID50Group 9: Infants, nOPV1 10^6.0 CCID50Groups 18, 20 & 22: Neonates, mOPV1Groups 2, 4 and 6: Young Children, mOPV1Groups 8, 10, 12, 12b, 14, 16: Infants mOPV1

Drop counts of nOPV vaccine will be varied to achieve approximately 10\^5.5, 10\^6.0, 10\^6.5 CCID50 or 10\^7.0, 10\^7.5 dose levels.

Group 11: Infants, nOPV1 10^6.5 CCID50Group 11b: Infants, nOPV1 10^6.5 CCID50Group 13: Infants, nOPV1 10^7.0 CCID50Group 15: Infants, nOPV1 10^7.5 CCID50Group 17: Neonates, nOPV1 10^6.5 CCID50Group 19: Neonates, nOPV1 10^7.0 CCID50Group 1: Young Children, nOPV1 10^5.5 CCID50Group 21: Neonates, nOPV1 10^7.5 CCID50Group 3: Young Children, nOPV1 10^6.0 CCID50Group 5: Young Children, nOPV1 10^6.5 CCID50Group 7: Infants, nOPV1 10^5.5 CCID50Group 9: Infants, nOPV1 10^6.0 CCID50Groups 8, 10, 12, 12b, 14, 16: Infants mOPV1

Eligibility Criteria

Age0 Days - 4 Years
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17)

You may qualify if:

  • 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
  • Parent(s) or guardian(s) willing and able to provide written informed consent prior to performance of any study-specific procedure
  • Resides in study area and parent 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)
  • Parent agrees for participant to receive all routine infant and childhood immunizations as per the approved protocol-adjusted schedule
  • Male or female child from 1 to less than 5 years of age at the time of initial study vaccination
  • Based on documentation, previously received a 3 or 4 dose primary poliomyelitis immunization series containing OPV (may have also received IPV), with last dose received more than 3 months prior to initial study vaccination
  • Male or female infant expected to be 6 weeks of age (43rd to 49th day of life \[with day of birth being the first day of life\], inclusive+ 6-day window), at the time of initial study vaccination
  • Prior to study vaccination has received no doses of IPV or OPV, based on no evidence of such vaccination per available documentation.
  • Male or female newborn (1st day of life+ 3-day window, inclusive), at the time of initial study vaccination
  • Prior to study vaccination has received no doses of IPV or OPV or rotavirus vaccine, based on no evidence of such vaccination per available documentation.

You may not qualify if:

  • For all participants, the 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 at the time of study vaccine administration. For household members younger than 10 years of age, "age appropriate" vaccination is complete series of trivalent Oral Poliovirus Vaccine (tOPV) or at least three doses of bivalent (types 1 and 3) Oral Poliovirus Vaccine (bOPV) plus a booster fractional dose of IPV (fractional dose Inactivated Polio Vaccine; fIPV). Note: A vaccination series of tOPV or at least three doses of bOPV with our without a booster fractional dose of IPV will be considered sufficient.
  • For all participants, having a member of the participant's household (living in the same house or apartment unit) who has received OPV based on the vaccination records in the previous 3 months before study vaccine administration.
  • Any participating children attending day care or pre-school during their participation in the study until one month after their last study vaccine administration.
  • A known allergy, hypersensitivity, or intolerance to any components of the study vaccines, including all macrolide and aminoglycoside antibiotics (e.g., erythromycin and kanamycin)
  • Evidence of a clinically significant congenital or genetic defect as judged by the investigator
  • History of chronic administration (defined as more than 14 days) of immunosuppressant medications, including corticosteroids (\> 0.5mg/kg/day of prednisolone (or equivalent)). Topical and inhaler steroids are permitted (unless indicative of a significant chronic illness otherwise excluding the infant/young child)
  • 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)
  • Receipt of any immune-modifying or immunosuppressant drugs within 6 months prior to the first study vaccine dose or planned use during the study of study participants or a household member
  • Any known or suspected bleeding disorder in the participant that would pose a risk to venipuncture or intramuscular injection
  • Participation in another investigational product (drug or vaccine) 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 tot he first administration of study vaccine, or planned use during the study period.
  • Receipt of transfusion of any blood product or immunoglobulins within 12 months prior to the first administration of study vaccine or planned use during the study period.
  • Parent or participant has any condition that in the opinion of the investigator would increase the participant's health risks in the 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.)
  • Low birth weight (LBW) in newborn participants which is defined as a birth weight of less than 2500g (up to and including 2499b) at the time of birth or by the time of enrolment.
  • Premature birth (less than 37 weeks gestation)
  • From multiple birth (due to increased risk of OPV transmission between siblings)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b)

Dhaka, 1212, Bangladesh

RECRUITING

MeSH Terms

Conditions

Poliomyelitis

Condition Hierarchy (Ancestors)

MyelitisCentral Nervous System InfectionsInfectionsEnterovirus InfectionsPicornaviridae InfectionsRNA Virus InfectionsVirus DiseasesCentral Nervous System DiseasesNervous System DiseasesSpinal Cord DiseasesNeuroinflammatory DiseasesNeuromuscular Diseases

Study Officials

  • K. Zaman, MBBS, MPH, PhD, FRCP

    International Centre for Diarrhoeal Disease Research, Bangladesh

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Tushar Tewari, MD

CONTACT

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
SEQUENTIAL
Model Details: A 15-arm, randomized, observer-blind, controlled, age de-escalation, dosage escalation study.
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 10, 2022

First Posted

December 9, 2022

Study Start

March 27, 2023

Primary Completion (Estimated)

May 15, 2026

Study Completion (Estimated)

May 15, 2026

Last Updated

January 9, 2026

Record last verified: 2026-01

Data Sharing

IPD Sharing
Will not share

Locations