A Study to Evaluate the Safety and Immunogenicity of Novel Oral Polio Vaccine

NCT03554798 | Completed Phase 2 Results DMC

• 1 other identifier: M5 ABMG
• Study Type: interventional
• Target: 1,025
• Locations: 1 country
• Sites: 2

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.

Conditions

Poliomyelitis

Outcome Measures

Primary Outcomes (2)

• Serious Adverse Reactions (SARs), Severe AEs and Important Medical Reactions (IMRs) Incidence

  Number of subjects experiencing Serious Adverse Reactions (SAR), severe AR and IMR, i.e. SAEs, severe AEs (grade 3), or IMEs considered consistent with a causal association with study vaccines as of the informed consent signature date and throughout the study period in all groups.

  6 months

• Single Dose Seroprotection Rate

  Seroprotection rate of type 2 polio neutralizing antibodies at Day 28 following a single 105 or 106 CCID50 dose of nOPV2 candidates in all groups. Seroprotection rate is defined as the percentage of subjects with type 2-specific antibody titers ≥ 1:8 per group.

  2 months

Secondary Outcomes (5)

• Any Other SAEs, AEs and IMEs Incidence

  6 months

• Seroconversion Rates Comparison

  2 months

• Seroprotection Rates Comparison

  2 months

• Viral Shedding

  2 months

• Neurovirulence

  2 months

Study Arms (2)

nOPV2 Candidate 1 (monovalent oral poliovirus type1)

EXPERIMENTAL

Cohort A: IPV and/or OPV vaccinated participants aged 1 to 5 years vaccinated with candidate 1. Cohort B: 6 weeks Infants vaccinated with 3 doses of bOPV and 1 dose of IPV, followed with 1 dose of candidate 1.

Biological: nOPV2 (monovalent oral polio vaccine)

nOPV2 Candidate 2 (monovalent oral poliovirus type2)

EXPERIMENTAL

Cohort A: IPV and/or OPV vaccinated participants aged 1 to 5 years vaccinated with candidate 2. Cohort B: Infants vaccinated with 3 doses of bOPV and 1 dose of IPV, followed with 1 dose of candidate 2.

Biological: nOPV2 (monovalent oral polio vaccine)

Interventions

nOPV2 (monovalent oral polio vaccine) BIOLOGICAL

Cohort A: 150 IPV and/or OPV vaccinated participants aged 1 to 5 years vaccinated with candidate 1 or 2; two 10‸6 CCID50 (50% cell culture infective dose) doses separated by 28 days. Cohort B: 972 infants enrolled at 6 weeks of age (-7 to +14 days) vaccinated with 3 doses of bOPV at 6, 10 and 14 weeks of age and 1 dose of IPV at 14 weeks of age, followed at 18-22 weeks of age with one 10‸5 CCID50 dose of candidate 1 or 2.

nOPV2 Candidate 1 (monovalent oral poliovirus type1); nOPV2 Candidate 2 (monovalent oral poliovirus type2)

Eligibility Criteria

• Age: 6 Weeks - 5 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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.
• 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.
• 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.
• Written informed consent obtained from 1 or 2 parent(s) or legal guardian(s) as per country regulations.

You may not qualify if:

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• Family history of congenital or hereditary immunodeficiency.
• Major congenital defects or serious uncontrolled chronic illness (neurologic, pulmonary, gastrointestinal, hepatic, renal, or endocrine).
• Known allergy to any component of the study vaccines or to any antibiotics, that share molecular composition with the nOPV2 vaccines.
• Uncontrolled coagulopathy or blood disorder contraindicating intramuscular injections (of IPV).
• Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.
• 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.

Sponsors & Collaborators

• Fidec Corporation: lead
• Bill and Melinda Gates Foundation: collaborator

Study Sites (2)

Cevaxin Vaccination Center

David, Chiriquí Province, Panama

Location

Cevaxin Vaccination Center

Panama City, Panama

Location

Related Publications (2)

• Wahid R, Mercer LD, De Leon T, DeAntonio R, Saez-Llorens X, Macadam A, Chumakov K, Strating J, Koel B, Konopka-Anstadt JL, Oberste MS, Burns CC, Andino R, Tritama E, Bandyopadhyay AS, Aguirre G, Ruttimann R, Gast C, Konz JO. Genetic and phenotypic stability of poliovirus shed from infants who received novel type 2 or Sabin type 2 oral poliovirus vaccines in Panama: an analysis of two clinical trials. Lancet Microbe. 2022 Dec;3(12):e912-e921. doi: 10.1016/S2666-5247(22)00254-3. Epub 2022 Nov 1.

  PMID: 36332645 DERIVED

• 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.

  PMID: 33308427 DERIVED

MeSH Terms

Conditions

Poliomyelitis

Condition Hierarchy (Ancestors)

Myelitis; Central Nervous System Infections; Infections; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Virus Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Neuroinflammatory Diseases; Neuromuscular Diseases

Results Point of Contact

• Title: Ricardo Rüttimann, PhD
• Organization: FIDEC Corporation

rruttimann@fidec-online.org

+5491161188536

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Allocation of each subject to a given group will be described in a computer-generated randomization schedule. Based on this randomization code, the study vaccine will be packaged and labeled. Medication code numbers will be preprinted on the study vaccine labels and assigned as subjects qualify for the study and are randomly assigned to dosing schedule.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2018
• First Posted: June 13, 2018
• Study Start: December 4, 2018
• Primary Completion: February 19, 2020
• Study Completion: February 19, 2020
• Last Updated: January 19, 2024
• Results First Posted: March 23, 2022

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

PA (2)