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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03554798
Recruitment Status : Completed
First Posted : June 13, 2018
Results First Posted : March 23, 2022
Last Update Posted : March 23, 2022
Sponsor:
Collaborator:
Bill and Melinda Gates Foundation
Information provided by (Responsible Party):
Fidec Corporation

Tracking Information
First Submitted Date  ICMJE May 8, 2018
First Posted Date  ICMJE June 13, 2018
Results First Submitted Date  ICMJE January 20, 2022
Results First Posted Date  ICMJE March 23, 2022
Last Update Posted Date March 23, 2022
Actual Study Start Date  ICMJE December 4, 2018
Actual Primary Completion Date February 19, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 20, 2022)
  • Serious Adverse Reactions (SARs), Severe AEs and Important Medical Reactions (IMRs) Incidence [ Time Frame: 6 months ]
    Incidence of 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.
  • Single Dose Seroprotection Rate [ Time Frame: 2 months ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: June 12, 2018)
  • Serious Adverse Reactions (SARs), severe AEs and Important Medical Reactions (IMRs) incidence [ Time Frame: 6 months ]
    Incidence of serious adverse reactions [SARs] and severe adverse events [AEs; grade 3 according to CTCAE 4.03], and important medical reactions [IMR]) in all groups after one dose of each dose level of the two nOPV2 vaccine candidates considered consistent with a causal association to study vaccine. Separate tables and listings will be created for subjects who died, discontinued the study vaccine due to an AE, or experienced a severe or serious AE. Summaries, listings, and narratives may be provided, as appropriate.
  • Single dose seroprotection rate [ Time Frame: 2 months ]
    To assess and compare the seroprotection rate against poliovirus type 2 of a single dose (at both 105 and 106 CCID50 dose levels) of each of the two nOPV2 vaccine candidates in infants at approximately 18-22 weeks of age after having been previously vaccinated with 3 doses of bOPV and 1 dose of IPV, relative to a control sample of infants receiving the same vaccination schedule followed by a single dose of Sabin mOPV2 in a prior study (M2) designed to serve as a historical control for the current study
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 20, 2022)
  • SAEs, AEs and IMEs Incidence [ Time Frame: 6 months ]
    Incidence, severity and causality of any other SAE, any solicited AE, any unsolicited AEs and any IME as well as any clinical laboratory deviation considered consistent with causal association to study vaccine (primary objective) following one or two doses of either nOPV2 candidates.
  • Seroconversion Rates Comparison [ Time Frame: 2 months ]
    Seroconversion rates against type 2 of one or two 106 CCID50 doses of both nOPV2 vaccine candidates in healthy children aged 1 to 5 years and of two doses of both nOPV2 vaccine candidates at both 105 and 106 CCID50 dose levels at approximately 22 weeks of age in infants previously vaccinated with 3 doses of bOPV and 1 dose of IPV, and compare this immunogenicity with a control sample of participants receiving the same vaccination schedule followed by one or two doses of Sabin mOPV2 in a prior study (M2) designed and performed to serve as a control for the current study. Seroconversion is defined as a change from seronegative to seropositive, and in seropositive subjects, as an antibody titer increase of ≥ 4 fold over baseline (Day 0) titers corrected for maternal antibodies titers where applicable/age-appropriate.
  • Seroprotection Rates Comparison [ Time Frame: 2 months ]
    Seroprotection rates against type 2 of one or two 106 CCID50 doses of both nOPV2 vaccine candidates in healthy children aged 1 to 5 years and of two doses of both nOPV2 vaccine candidates at both 105 and 106 CCID50 dose levels at approximately 22 weeks of age in infants previously vaccinated with 3 doses of bOPV and 1 dose of IPV, and compare this immunogenicity with a control sample of participants receiving the same vaccination schedule followed by one or two doses of Sabin mOPV2 in a prior study (M2) designed and performed to serve as a control for the current study.
  • Viral Shedding [ Time Frame: 2 months ]
    Level of viral shedding in stool at fixed time points following administration of one or two doses of both nOPV2 candidates at both 105 and 106 CCID50 dose levels in infants at approximately 18-22 weeks of age after having been previously vaccinated with 3 doses of bOPV and 1 dose of IPV, and compare this shedding to a control sample of participants receiving the same vaccination schedule followed by one or two doses of Sabin mOPV2 in a prior study designed to serve as a control for the current study.
  • Neurovirulence [ Time Frame: 2 months ]
    Potential for neurovirulence of virus isolated from a subset of stool samples of infants at approximately 18-22 weeks of age after having been previously vaccinated with 3 doses of bOPV and 1 dose of IPV, and following a single dose of both nOPV2 candidates at the 106 CCID50 dose level, as measured in an animal model, and compare this with a control sample of participants receiving the same vaccination schedule followed by a single dose of Sabin mOPV2 in a prior study (M2) designed to serve as a control for the current study.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 12, 2018)
  • SAEs, AEs and IMEs incidence [ Time Frame: 6 months ]
    Incidence, severity and causality of any other SAE, any solicited AE, any unsolicited AEs and any IME as well as any clinical laboratory deviation considered consistent with causal association to study vaccine (primary objective) following one or two doses of either nOPV2 candidates.
  • Seroconversion rates comparison [ Time Frame: 2 months ]
    To assess the seroconversion rates against type 2 of one or two 106 CCID50 doses of both nOPV2 vaccine candidates in healthy children aged 1 to 5 years and of two doses of both nOPV2 vaccine candidates at both 105 and 106 CCID50 dose levels at approximately 22 weeks of age in infants previously vaccinated with 3 doses of bOPV and 1 dose of IPV, and compare this immunogenicity with a control sample of participants receiving the same vaccination schedule followed by one or two doses of Sabin mOPV2 in a prior study (M2) designed and performed to serve as a control for the current study. Seroconversion is defined as a change from seronegative to seropositive, and in seropositive subjects, as an antibody titer increase of ≥ 4 fold over baseline (Day 0) titers corrected for maternal antibodies titers where applicable/age-appropriate.
  • Seroprotection rates comparison [ Time Frame: 2 months ]
    To assess the seroprotection rates against type 2 of one or two 106 CCID50 doses of both nOPV2 vaccine candidates in healthy children aged 1 to 5 years and of two doses of both nOPV2 vaccine candidates at both 105 and 106 CCID50 dose levels at approximately 22 weeks of age in infants previously vaccinated with 3 doses of bOPV and 1 dose of IPV, and compare this immunogenicity with a control sample of participants receiving the same vaccination schedule followed by one or two doses of Sabin mOPV2 in a prior study (M2) designed and performed to serve as a control for the current study.
  • Viral shedding [ Time Frame: 2 months ]
    To assess the extent of viral shedding in stool at fixed time points following administration of one or two doses of both nOPV2 candidates at both 105 and 106 CCID50 dose levels in infants at approximately 18-22 weeks of age after having been previously vaccinated with 3 doses of bOPV and 1 dose of IPV, and compare this shedding to a control sample of participants receiving the same vaccination schedule followed by one or two doses of Sabin mOPV2 in a prior study designed to serve as a control for the current study.
  • Neurovirulence [ Time Frame: 2 months ]
    To assess the potential for neurovirulence of virus isolated from a subset of stool samples of infants at approximately 18-22 weeks of age after having been previously vaccinated with 3 doses of bOPV and 1 dose of IPV, and following a single dose of both nOPV2 candidates at the 106 CCID50 dose level, as measured in an animal model, and compare this with a control sample of participants receiving the same vaccination schedule followed by a single dose of Sabin mOPV2 in a prior study (M2) designed to serve as a control for the current study.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate the Safety and Immunogenicity of Novel Oral Polio Vaccine
Official Title  ICMJE 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
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description:
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.
Primary Purpose: Prevention
Condition  ICMJE Poliomyelitis
Intervention  ICMJE Biological: nOPV2 (monovalent oral polio vaccine)

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.

Study Arms  ICMJE
  • Experimental: nOPV2 Candidate 1 (monovalent oral poliovirus type1)

    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.

    Intervention: Biological: nOPV2 (monovalent oral polio vaccine)
  • Experimental: nOPV2 Candidate 2 (monovalent oral poliovirus type2)

    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.

    Intervention: Biological: nOPV2 (monovalent oral polio vaccine)
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 20, 2022)
1025
Original Estimated Enrollment  ICMJE
 (submitted: June 12, 2018)
748
Actual Study Completion Date  ICMJE February 19, 2020
Actual Primary Completion Date February 19, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Weeks to 5 Years   (Child)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Panama
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03554798
Other Study ID Numbers  ICMJE M5 ABMG
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Fidec Corporation
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Fidec Corporation
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Bill and Melinda Gates Foundation
Investigators  ICMJE Not Provided
PRS Account Fidec Corporation
Verification Date January 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP