A Study to Evaluate the Safety and Immunogenicity of Oral Polio Vaccine Type 2 in Infants and Children (M2-ABMG)

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

Sabin 2 will be withdrawn from routine use globally from April 2016 as per the SAGE recommendations at the time of writing this protocol.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.

Study Overview

• Status: Completed
• Conditions: Adverse Event Following Immunisation
• Intervention / Treatment: Biological: SABIN monovalent OPV2

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 .

• Study Type: Interventional
• Enrollment (Actual): 164
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 5 years (CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: SABIN monovalent OPV2 vaccine; SABIN monovalent OPV2 is a licensed, monovalent, live attenuated poliomyelitis virus vaccine of the Sabin strain Type 2 (P 712, Ch, 2ab), propagated in MRC5 human diploid	Biological: SABIN monovalent OPV2; SABIN monovalent OPV2 is a licensed, monovalent, live attenuated poliomyelitis virus vaccine of the Sabin strain Type 2 (P 712, Ch, 2ab), propagated in MRC5 human diploid cells. Each two-drop dose (0.1 mL) contains not less than 105.0 CCID50 of Type 2; Other Names: Polio Sabin™ Mono Two (oral)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects Experiencing SAEs, Severe AEs (Grade 3), and/or IMEs	Number of subjects experiencing SAEs, severe AEs (grade 3), and IMEs considered consistent with a causal association to study vaccine throughout the study period in all groups.	6 months
Seroprotection Rate of Type 2 Polio Neutralizing Antibodies.	Measured at Day 28 following a single dose of Sabin mOPV2 in both infant groups (Groups 2+3). Seroprotection is defined as type 2-specific antibody titers ≥1:8 and seroprotection rate as the percentage of seroprotected subjects per group.	28 days

Collaborators and Investigators

• Sponsor: Fidec Corporation
• Collaborators: Bill and Melinda Gates Foundation
• Investigators: Principal Investigator: Xavier M Saez-Llorens, MD, Hospital del Niño de Panama

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 1, 2015
• Primary Completion (ACTUAL): July 1, 2016
• Study Completion (ACTUAL): September 29, 2016

Study Registration Dates

• First Submitted: July 31, 2015
• First Submitted That Met QC Criteria: August 12, 2015
• First Posted (ESTIMATE): August 13, 2015

Study Record Updates

• Last Update Posted (ACTUAL): August 14, 2020
• Last Update Submitted That Met QC Criteria: August 1, 2020
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Other Study ID Numbers: M2-ABMG