Clinical trial NCT02189811: Polio End-game Strategies - Poliovirus Type 2 Challenge Study
Official title: Polio End-game Strategies - Poliovirus Type 2 Challenge Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Poliomyelitis
Keywords: IPV
OPV
tOPV
bOPV
Polio
Endgame
Pakistan
Lead sponsor: Aga Khan University
Sponsor class: OTHER
Collaborators: name: World Health Organization
name: Centers for Disease Control and Prevention
name: National Institutes of Health (NIH)
First posted: 2014-07-15
Enrollment: 900
Sex: ALL
Maximum age (years): 1
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Poliomyelitis eradication has entered its last phase with only three remaining endemic countries, of which Pakistan is one. There hasn't been a case of wild type poliovirus 2 since 1999, and no case of wild type poliovirus 3 since November 2012. However, paralytic polio resulting from circulating strains of Sabin poliovirus type 2 have become a challenge, and reported from several areas with low population immunity to polio, including in Pakistan. This study will provide data to National Immunization Authorities in order to make strategic decisions about their polio vaccination schedules in anticipation of the global tOPV to bOPV switch and will provide data on the proposed responses to type 2 poliovirus outbreaks.

Detailed description: The "Polio Endgame Strategy" consists of set of tasks and activities that will be implemented in the next five years. It includes gradual withdrawal of the widely used oral poliomyelitis vaccine (OPV) containing live poliovirus, and will eventually lead to complete eradication and containment of all wild, vaccine-related (VDPV) and Sabin polioviruses. The withdrawal of the type 2 components of trivalent OPV (tOPV) is the key component in the elimination of cVDPVs. This entails strengthening of the immunization system by introducing at least one dose of affordable IPV into the routine immunization schedule globally and then replacing the trivalent OPV with bivalent OPV in all OPV-using countries - setting the stage for eventually ending bOPV use in 2019-2020. Most of the developing countries have an OPV schedule however many developed and European countries follow the IPV only schedule. The current recommendations for polio eradication and endgame is IPV vaccine to be administered together with third OPV dose, which in most countries occurs at 14 weeks of age.

This study will assess the protection to type 2 poliovirus achieved after completion of the recommended schedule with bOPV and IPV; it will compare immunogenicity of bOPV + IPV schedule with tOPV only schedule; and will quantify the cross-reactivity of bOPV on inducing type 2 immunological reaction. In addition, it will also provide first data on the proposed outbreak response to type 2 (either with mOPV 2 or with a combination of mOPV 2 and IPV 2).

This study will provide data to National Immunization Authorities in order to make strategic decisions about their polio vaccination schedules in anticipation of the global tOPV to bOPV switch and will provide data on the proposed responses to type 2 poliovirus outbreaks.

Eligibility criteria: Inclusion Criteria:

* Newborn of either gender born healthy with birth weight 2.0 kg or more, with immediate cry, at the study sites (home or health facility births)
* Not planning to travel away during entire the study period (birth-154 days; birth 22 weeks).
* Parents resident of the study area for last 3 month at the time of enrolment
* Parent/guardian provides informed consent

Exclusion Criteria:

* Newborns found acutely ill at the time of enrolment and requiring emergent medical care/hospitalization, birth weight below 2.0 kg, cry \>2 minutes after birth, or family is planning to be absent during the birth - 154 days study period
* Refusal of blood testing and cord blood testing
* Receipt of OPV after birth before eligibility screen
* Newborns with certain medical conditions i.e., syndromic infants, neonate with petechial or purpura (contraindication of intramuscular injections)
* A diagnosis or suspicion of immunodeficiency disorder (either in the participant or in a member of the immediate family - e.g. several early infant deaths, household member on chemotherapy) will render the newborn ineligible for the study.

Primary outcomes:
measure: Difference in seroprevalence of neutralizing antibodies for type 2 in 19 weeks of age between arms
timeFrame: 19 weeks of age
Secondary outcomes:
measure: Seroprevalence of neutralizing antibodies at 18 weeks of age
timeFrame: 18 weeks of age
Other outcomes:
measure: Difference in shedding of poliovirus type 2 in stool in 19 weeks of age between arms
timeFrame: 19 weeks of age
measure: Difference in seroprevalence of neutralizing antibodies at 22 weeks of age between arms
timeFrame: 22 weeks of age
Locations:
city: Karachi
country: Pakistan
facility: Rehri goth, Ibrahim Hyderi, Ali Akbar Shah, and Bhens Colony
state: Sindh
Study officials:
affiliation: Aga Khan University
name: Ali F Saleem, MBBS,FCPS,MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Saleem AF, Yousafzai MT, Mach O, Khan A, Quadri F, Weldon WC, Oberste MS, Zaidi SS, Alam MM, Sutter RW, Zaidi AKM. Evaluation of vaccine derived poliovirus type 2 outbreak response options: A randomized controlled trial, Karachi, Pakistan. Vaccine. 2018 Mar 20;36(13):1766-1771. doi: 10.1016/j.vaccine.2018.02.051. Epub 2018 Feb 21.