Clinical trial NCT07010822: A Study to Evaluate the Mucosal Intestinal Immunity to Poliovirus Type-2 of nOPV2 at Birth Dose in Healthy IPV Vaccinated Infants
Official title: A Phase III, Double-blind, Randomized, Controlled Study to Evaluate the Mucosal Intestinal Immunity to Poliovirus Type-2 of nOPV2 at Birth Dose in Healthy IPV Vaccinated Infants
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Poliomyelitis
Keywords: Polio
nOPV2
immunity
Lead sponsor: Fidec Corporation
Sponsor class: OTHER
Collaborators: name: Bill and Melinda Gates Foundation (Funder)
First posted: 2025-06-08
Enrollment: 740
Sex: ALL
Minimum age (years): 1
Maximum age (years): 7
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The study will compare the transmissible levels of poliovirus type-2 detected in stool samples collected at the time of the nOPV2 challenge and subsequent timepoints in 3 groups of newborns receiving an nOPV2 dose at birth and primed with 3 doses of IPV (6 - 10 - 14 weeks of age).

Detailed description: To meet the urgent public health need regarding cVDPV2 outbreaks, a novel type 2 OPV (nOPV2) vaccine was developed using attenuated serotype 2 polioviruses derived from a modified Sabin 2 infectious cDNA clone generated by modifying the Sabin-2 ribonucleic acid (RNA) sequence to improve genetic stability and make the strains less prone to reversion to virulence. Clinical trials in adults, children, and infants demonstrated that nOPV2 vaccine is safe, well tolerated, and immunogenic. These include a phase 2 study of vaccine-naïve neonates in Bangladesh who received either two doses of nOPV2 or two doses of placebo at birth and 4 weeks of age concluded that the vaccine was well tolerated and immunogenic, as 90% of the infants seroconverted at 2 weeks post second dose. Overall 99% of infants had protective levels of neutralizing antibody at this time in contrast to the seroprotection rate of 56% in the placebo group.

Although immunogenic, the effect of nOPV2 on virus transmission is still unclear. This phase 3 study aims to compare the transmissible levels of poliovirus type-2 detected in stool samples collected at the time of the nOPV2 challenge (pre-challenge) and subsequent timepoints in 3 groups of newborns receiving an nOPV2 dose at birth and primed with 3 doses of IPV (6 - 10 - 14 weeks of age).

Eligibility criteria: Inclusion Criteria:

1. Newborn infants of maximum 1 week of age with birth weight \> 2,500 g.
2. Healthy infants without obvious medical conditions like immunodeficiency diseases, severe congenital malformations, severe neurological diseases or any other disease that require high doses of corticosteroids or immunotherapies that preclude the subject from participating in the study as established by medical history and physical examination.
3. Written informed consent obtained from both parents or legal guardian(s) as per country regulations.

Exclusion Criteria:

1. Any confirmed or suspected immunosuppressive or known immunodeficient condition including human immunodeficiency virus infection in the potential participant or any member of the subject's household.
2. Family history of congenital or hereditary immunodeficiency.
3. Major congenital defects or serious uncontrolled chronic illness (neurologic, pulmonary, gastrointestinal, hepatic, renal, or endocrine).
4. Known allergy to any component of the study vaccines or to any antibiotics that share molecular composition with a component of the study vaccines.
5. Uncontrolled coagulopathy or blood disorder contraindicating intramuscular injections (of IPV)
6. Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.
7. Acute severe febrile illness on the day of vaccination deemed by the Investigator to be a contraindication for vaccination (the child can be included at a later time if within age window and all inclusion criteria are met.).
8. Subject who, in the opinion of the Investigator, is unlikely to comply with the protocol or is inappropriate to be included in the study for the safety or the benefit-risk ratio of the subject.
9. Infants from multiple births or born prematurely (\< 37 weeks of gestation).

Primary outcomes:
measure: Stool viral load
timeFrame: From enrollment to the end of the study at Wk 22 of age.
Secondary outcomes:
measure: PV Type 2 neutralizing activity in stool samples
timeFrame: From enrollment to the end of the study at 22 Wks of age.
measure: PV Type 2 AUC and SIE in stool samples
timeFrame: From enrollment to the end of the study at 22 Wks of age
measure: PV Type 2 seroprotection rate
timeFrame: From enrollment till 18 Wks of age
measure: PV Type 2 seroconversion rate
timeFrame: From enrollment till Wk 18 of age.
measure: PV Type 2 neutralization titers
timeFrame: From enrollment till Wk 18 of age
measure: SAEs and IMEs
timeFrame: From enrollment to the end of the study at Wk 22 of age
measure: Solicited AEs
timeFrame: From enrollment to Wk 18 of age
Other outcomes:
Locations:
city: Chandpur
country: Bangladesh
facility: icddr,b - Matlab Health Research Centre
state: Dhaka
Study officials:
affiliation: International Centre for Diarrhoeal Disease Research, Bangladesh
name: Khaelqu Zaman, Dr.
role: PRINCIPAL_INVESTIGATOR
References: