Clinical Trial of Novel OPV2 Vaccine

Summary

Though OPV is safe and effective, it can mutate and reacquire neurovirulence in rare circumstances. This can result in vaccine-associated paralytic polio and circulating vaccine-derived polioviruses. Use of tOPV had risk of generating VAPP and seeding new type 2 circulating vaccine-derived polioviruses though wild type 2 virus was eradicated in September 2015. For this reason tOPV vaccine was withdrawn globally in April 2016 and switched to bOPV. cVDPV2 outbreaks have occurred in sixteen countries after cassation of OPV2. Using stockpiled mOPV2 to respond to this situation risks propagating new cVDPVs. IPV induces only limited intestinal mucosal immunity not effective to interrupt fecal-oral route transmission in settings of poor hygiene and sanitation. Therefore, development of novel oral polio vaccine with enhanced genetic stability and lower risk of reversion to neurovirulence compared to current Sabin 2 strains is major priority of global polio eradication Program

Current clinical development plan outlines studies through Phase II development with nOPV2 candidate strains being tested in adult toddler and infant populations who received prior dose of OPV or IPV. No study has been conducted in truly naive newborns with no prior receipt of any polio vaccines

Hypothesis: Vaccinating healthy newborns with novel type 2 polio virus candidate vaccines is safe and can induce putatively protective immune response

Objectives

Primary Objective

Safety

To evaluate the safety and tolerability after one and two doses of nOPV2 vaccine candidates 1 given 4 weeks apart in poliovirus vaccine-naïve newborn Immunogenicity To evaluate the immune response to vaccination after one and two doses of nOPV2 vaccine candidate 1 given 4 weeks apart in poliovirus vaccine-naïve newborns

Secondary objectives

Immunogenicity

To evaluate seroprotection rate geometric mean and median titers to vaccination after one dose of nOPV2 vaccine candidate 1 in poliovirus vaccine-naïve newborns To further evaluate seroprotection rate geometric mean and median titers to vaccination after two doses of nOPV2 candidate 1 in poliovirus vaccine-naïve newborns

Viral Shedding

To assess trate of fecal viral shedding at fixed time points following one and two doses of nOPV2 vaccine candidate 1 in newborns To assess duration of fecal viral shedding at fixed time points following one and two doses of nOPV2 vaccine candidate 1 in newborns To assess extent of fecal viral at fixed time points following one and two doses of nOPV2 vaccine candidate 1 in newborns

Exploratory objective

To assess genetic stability through genetic deep sequencing assay and neurovirulence test through transgenic mice NV assays from a subset of participants stools samples

Conditions

• Poliomyelitis

Interventions

BIOLOGICAL

novel oral polio type 2 vaccine (nOPV2)

• nOPV2 (C1) is a live-attenuated serotype-2 poliovirus that was derived from a modified Sabin type-2 infectious cDNA clone and propagated in Vero cells (S2/cre5/S15domV/rec1/hifi3). Placebo contain sucrose in buffer.

OTHER

Placebo

Placebo contains no active ingradients, only sucrose in buffer

Sponsors & Collaborators

• Bill and Melinda Gates Foundation

  collaborator OTHER

• Centers for Disease Control and Prevention

  collaborator FED

• PATH

  collaborator OTHER

• World Health Organization

  collaborator OTHER

• PT Bio Farma

  collaborator INDUSTRY

• International Centre for Diarrhoeal Disease Research, Bangladesh

  lead OTHER

Principal Investigators

• K Zaman, PhD FRCP · International Centre for Diarrhoeal Disease Research, Bangladesh

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

1 Hour

Max Age

3 Days

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2020-09-21

Primary Completion

2021-08-30

Completion

2021-08-30

Countries

• Bangladesh

Study Locations