Clinical trial NCT02521974: A Study to Evaluate the Safety and Immunogenicity of Oral Polio Vaccine Type 2 in Infants and Children
Official title: A Phase 4 Study to Evaluate the Safety and Immunogenicity of Monovalent Oral Polio Vaccine Type 2 in Healthy Children Aged 1 to 5 Years and in bOPV-IPV Vaccinated Healthy Infants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Adverse Event Following Immunisation
Lead sponsor: Fidec Corporation
Sponsor class: OTHER
Collaborators: name: Bill and Melinda Gates Foundation
First posted: 2015-08-13
Enrollment: 164
Sex: ALL
Minimum age (years): 6
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: Sabin 2 will be withdrawn from routine use globally from April 2016 as per the SAGE recommendations at the time of writing this protocol. After this cessation of OPV2, stockpiles of mOPV2 will be maintained for potential use if necessary in response to a future outbreak. However, there will be a risk of cVDPV2 from Sabin 2 in settings of low population immunity. Research is ongoing to develop vaccines that are genetically more stable than the currently available Sabin 2-containing OPVs. To generate data on immunogenicity, safety, and genetic stability on the Sabin 2 vaccine (mOPV2) and as a future comparator for new polio vaccine research after the global switch from tOPV to bOPV, this study with mOPV2 is performed to evaluate safety, immunogenicity (humoral and intestinal) and genetic stability endpoints of mOPV2 in children aged 1 to 5 years and in infants approximately 18 weeks of aged vaccinated with bOPV-/IPV for better understanding of the stockpile use of this vaccine, and for comparison with any potential new polio vaccine with a type 2 component in the future.

Detailed description: 1. PRIMARY OBJECTIVE The primary objectives of the study are to assess the safety (serious adverse events \[SAEs\] and severe adverse events \[AEs\] grade 3 according to CTCAE 4.03 and immunogenicity (seroprotection rate) of a single dose of SABIN mOPV2 in healthy children aged 1 to 5 years old, and in infants at approximately 18 weeks of age after having been vaccinated with 3 doses of bOPV and 1 dose of IPV .
2. SECONDARY OBJECTIVES

   Secondary objectives are to assess:
   * The safety (mild and moderate solicited and unsolicited AEs, Important Medical Events \[IMEs\], and laboratory deviation assessments) of one or two doses of SABIN mOPV2 in healthy children aged 1 to 5 years, and of 2 doses of SABIN mOPV2 in infants at approximately 18 and 22 weeks of age after having been vaccinated with 3 doses of bOPV and 1 dose of IPV.
   * The immunogenicity (seroconversion rate, median and geometric mean antibody titers) of one or two doses of SABIN mOPV2 in healthy children aged 1 to 5 years old, and of two doses of SABIN mOPV2 in infants at approximately 18 22 weeks of age after having been vaccinated with 3 doses of bOPV and 1 dose of IPV.
3. EXPLORATORY OBJECTIVES

Exploratory objectives are:

* To investigate viral shedding following the SABIN mOPV2 administration.
* Exploratory objectives may also include assessment of the genetic sequence heterogeneity and potential for neurovirulence (as measured in animal model(s)) of shed virus.
* To investigate viral shedding and neurovirulence of shed virus;
* To evaluate genetic reversion at position nt481 (primarily) and other secondary sites (e.g., nt2908).
* To investigate the priming responses of bOPV for mOPV2. (group 2 only) and the duration of induction of anti-polio type 2 neutralizing antibodies .

Eligibility criteria: Inclusion Criteria:

1. Children aged 1 to 5 years previously vaccinated with three or four doses of IPV (Group 1) or unvaccinated infants aged 6 weeks (-7 to +14 days) (Groups 2 and 3).
2. For Groups 2 and 3 (enrolled at 6 weeks of age) infants must have been vaccinated with 3 doses of bOPV and one dose of IPV prior to administration of the study vaccine, and the last Polio vaccine must have been administered at least 4 weeks prior to the study vaccine.
3. Healthy without obvious medical conditions 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 Group 1: polio vaccines within the 3 months prior to the administration of the study vaccine (number of previous polio vaccine doses to be documented). For Groups 2 and 3: polio vaccines prior to administration of the study vaccine other than 3 doses of bOPV and 1 dose of IPV .
2. Any confirmed or suspected immunosuppressive or known immunodeficient condition including human immunodeficiency virus (HIV) infection.
3. Family history of congenital or hereditary immunodeficiency.
4. Major congenital defects or serious uncontrolled chronic illness (neurologic, pulmonary, gastrointestinal, hepatic, renal, or endocrine).
5. Known allergy to any component of the study vaccines or to any antibiotics.
6. Uncontrolled coagulopathy or blood disorder contraindicating intramuscular injections (of IPV).
7. Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.
8. 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 in/exclusion criteria are met.).
9. Member of the subject's household (living in the same house or apartment unit) has received OPV in the last 3 months.
10. 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: Number of Subjects Experiencing SAEs, Severe AEs (Grade 3), and/or IMEs
timeFrame: 6 months
measure: Seroprotection Rate of Type 2 Polio Neutralizing Antibodies.
timeFrame: 28 days
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Hospital del Niño de Panama
name: Xavier M Saez-Llorens, MD
role: PRINCIPAL_INVESTIGATOR
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.