Clinical trial NCT03554798: A Study to Evaluate the Safety and Immunogenicity of Novel Oral Polio Vaccine
Official title: A Phase 2 Study to Evaluate the Safety and Immunogenicity of Two Novel Oral Polio Type 2 (nOPV2) Vaccine Candidates in Healthy Children Aged 1 to 5 Years and in Healthy Bivalent Oral Polio Vaccine-inactivated Polio Vaccine (bOPV-IPV) Vaccinated Infants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Poliomyelitis
Lead sponsor: Fidec Corporation
Sponsor class: OTHER
Collaborators: name: Bill and Melinda Gates Foundation
First posted: 2018-06-13
Enrollment: 1025
Sex: ALL
Minimum age (years): 6
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This will be a single center, age de-escalation, partly-blinded, randomized study.

The trial will be performed with the participation of 100 healthy children age 1-5 years who have been vaccinated with inactivated polio vaccine (IPV) and/or oral polio vaccine (OPV) in their first year of life and of 648 healthy 6 week-old infants, who will be pre-vaccinated with bOPV-IPV before being randomized to study groups. The allocation of 18-22 week-old infants to groups will be performed in a randomized manner. Following completion and Data Safety Monitoring Board (DSMB) review of follow-up for general safety data (Serioius Adverse Events -SAEs-, Important Medical Events -IMEs- and severe adverse events -AEs), a DSMB recommendation to proceed will result in randomization of the final cohort of infants. Allocation of 1 to 5 year-old children to groups will be performed in a randomized manner.

The DSMB will establish and continuously assess stopping rules for safety.


Eligibility criteria: Inclusion Criteria:

1. For Cohort A children enrolled at 1 to 5 years of age who have previously been fully vaccinated according to MoH recommendations with OPV and/or IPV.
2. For Cohort B infants enrolled at 6 weeks of age (-1, + 2 weeks) with birth weight \>2,500 gm. To be eligible to continue into the experimental phase of the study infants must be vaccinated with 3 doses of bOPV and one dose of IPV prior to administration of the study vaccine at 18-22 weeks of age to take into account the visit windows for enrollment (age 6 weeks, -1 or + 2 weeks) and subsequent OPV vaccination windows (± 1 week). The last polio vaccine must have been administered at least 4 weeks prior to the first dose of study vaccine. Subjects in Cohort B who do not complete the three routine vaccination visits will be replaced in the study, and their parents/guardians will be encouraged to complete the primary vaccinations series.
3. Healthy children 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 to be in the study as established by the medical history and physical examination.
4. Written informed consent obtained from 1 or 2 parent(s) or legal guardian(s) as per country regulations.

Exclusion Criteria:

1. For all participants the presence of anyone under 10 years of age in the subject'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 18 months age appropriate vaccination is at least three (3) doses of IPV. For household members between 18 months and 10 years "age appropriate" vaccination is at least three (3) doses of IPV or tOPV plus one (1) booster dose of any antipolio vaccine.
2. For all participants having a member of the subject's household (living in the same house or apartment unit) who is under 6 months of age at the moment of study vaccine administration.
3. For all participants having a member of the subject's household (living in the same house or apartment unit) who has received OPV in the previous 3 months before study vaccine administration.
4. For Cohort A: receipt of polio vaccines within the 3 months prior to the administration of the study vaccine (number of previous polio vaccine doses to be documented). Any other vaccine 4 weeks before study entry.
5. For Cohort A: any participating children attending day care or pre-school during their participation in the study until one month after their last nOPV2 administration.
6. For Cohort B: any receipt of polio vaccines prior to administration of the study vaccine other than 3 doses of bOPV and 1 dose of IPV.
7. Any confirmed or suspected immunosuppressive or known immunodeficient condition including human immunodeficiency virus (HIV) infection in the potential participant or any member of the subject's household.
8. Family history of congenital or hereditary immunodeficiency.
9. Major congenital defects or serious uncontrolled chronic illness (neurologic, pulmonary, gastrointestinal, hepatic, renal, or endocrine).
10. Known allergy to any component of the study vaccines or to any antibiotics, that share molecular composition with the nOPV2 vaccines.
11. Uncontrolled coagulopathy or blood disorder contraindicating intramuscular injections (of IPV).
12. Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.
13. Acute severe febrile illness at 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.).
14. 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.

Primary outcomes:
measure: Serious Adverse Reactions (SARs), Severe AEs and Important Medical Reactions (IMRs) Incidence
timeFrame: 6 months
measure: Single Dose Seroprotection Rate
timeFrame: 2 months
Secondary outcomes:
measure: Any Other SAEs, AEs and IMEs Incidence
timeFrame: 6 months
measure: Seroconversion Rates Comparison
timeFrame: 2 months
measure: Seroprotection Rates Comparison
timeFrame: 2 months
measure: Viral Shedding
timeFrame: 2 months
measure: Neurovirulence
timeFrame: 2 months
Other outcomes:
Locations:
city: David
country: Panama
facility: Cevaxin Vaccination Center
state: Chiriquí
city: Panamá
country: Panama
facility: Cevaxin Vaccination Center
Study officials:
References:
citation: Saez-Llorens X, Bandyopadhyay AS, Gast C, Leon T, DeAntonio R, Jimeno J, Caballero MI, Aguirre G, Oberste MS, Weldon WC, Konopka-Anstadt JL, Modlin J, Bachtiar NS, Fix A, Konz J, Clemens R, Costa Clemens SA, Ruttimann R. Safety and immunogenicity of two novel type 2 oral poliovirus vaccine candidates compared with a monovalent type 2 oral poliovirus vaccine in children and infants: two clinical trials. Lancet. 2021 Jan 2;397(10268):27-38. doi: 10.1016/S0140-6736(20)32540-X. Epub 2020 Dec 9.