Clinical Trial of Novel OPV2 Vaccine

NCT04693286 | Completed Phase 2

• 1 other identifier: PR-20001
• Study Type: interventional
• Target: 330
• Locations: 1 country
• Sites: 1

Brief 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 For this reason tOPV vaccine was withdrawn globally in April 2016 and switched to bOPV.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

Keywords

Safety; Immunogenecity; nOPV2; Newborn; Bangladesh

Outcome Measures

Primary Outcomes (3)

• Safety of nOPV2 vaccine

  * Incidence rate of solicited systemic AEs within 7 days after each dose of vaccine * Incidence rate of unsolicited AEs during entire study period * Incidence rate of serious AEs and AESIs during entire study period

  Upto 3 months

• Immunogenecity of nOPV2 vaccine , will be assessed as poliovirus type-2-specific serum neutralising antibodies

  Proportion of participants showing seroconversion and seroprotection will be calculated and reported

  4 weeks

• Viral shedding in participants stool will be measured and reported by proportion of participants showing viral shedding in their stools, the time to cessation of viral shedding, the cell culture infective dose of shed virus in virus-positive stools

  Vaccine poliovirus shedding in the study participants stool will be assessed by real-time RT-PCR method.

  12 weeks

Secondary Outcomes (1)

• Genetic assay and Neurovirulance test to assess genetic stability by demonstrating the retention of key genetic regions engineered in the vaccine candidate

  4 weeks

Study Arms (2)

Vaccine candidate arm

ACTIVE COMPARATOR

In this arm, participants will get nOPV2 vaccine candidate 1

Biological: novel oral polio type 2 vaccine (nOPV2)

Placebo arm

PLACEBO COMPARATOR

In this arm, participants will get inactive substance like sucrose in BME media and buffer.

Other: Placebo

Interventions

novel oral polio type 2 vaccine (nOPV2) BIOLOGICAL

• 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.

Vaccine candidate arm

Placebo OTHER

Placebo contains no active ingradients, only sucrose in buffer

Placebo arm

Eligibility Criteria

• Age: 1 Hour - 3 Days
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Newborns at birth (range: 0-3 days of age).
• Mothers that consent for participation in the full length of the study.
• Mothers those are able to understand and comply with planned study procedures.

You may not qualify if:

• Mother and newborns who are unable to participate in the full length of the study.
• A diagnosis or suspicion of immunodeficiency disorder either in the newborn or in an immediate family member.
• A diagnosis or suspicion of bleeding disorder that would contraindicate collection of blood by venipuncture.
• Acute diarrhea, infection or illness at the time of enrollment that would require admission to a hospital.
• Acute vomiting and intolerance to liquids within 24 hours before the enrollment visit.
• Receipt of any polio vaccine (OPV or IPV) and Rotavirus Vaccine (RVV) before enrollment based upon documentation or mothers recall.
• Newborns from multiple births. Newborns from multiple births will be excluded to reduce the potential for contact transmission of vaccine poliovirus to siblings. The newborn from a multiple birth who is /are not enrolled would be likely to receive routine immunization and transmit vaccine poliovirus to the enrolled infant.
• Newborns from premature births (\<37 weeks of gestation).

Sponsors & Collaborators

• International Centre for Diarrhoeal Disease Research, Bangladesh: lead
• Bill and Melinda Gates Foundation: collaborator
• Centers for Disease Control and Prevention: collaborator
• PATH: collaborator
• World Health Organization: collaborator
• PT Bio Farma: collaborator

Study Sites (1)

: International Centre for Diarrhoeal Disease Research, Bangladesh

Dhaka, 1212, Bangladesh

Location

Related Publications (2)

• Godin A, Brickley EB, Connor RI, Wieland-Alter WF, Weiner JA, Ackerman ME, Modlin JF, Sajjad OM, Arita M, Gast C, Mainou BA, Zaman K, Hoque M, Rana S, Bandyopadhyay AS, Wright PF. Intestinal mucosal immune responses to novel oral poliovirus vaccine type 2 in healthy newborns. Clin Infect Dis. 2025 Sep 5:ciaf484. doi: 10.1093/cid/ciaf484. Online ahead of print.

  PMID: 40907970 DERIVED

• Zaman K, Bandyopadhyay AS, Hoque M, Gast C, Yunus M, Jamil KM, Mainou BA, Konopka-Anstadt JL, Hendley WS, Vincent A, Clemens R, Clemens SAC, Ross AG, Clemens JD, Tritama E. Evaluation of the safety, immunogenicity, and faecal shedding of novel oral polio vaccine type 2 in healthy newborn infants in Bangladesh: a randomised, controlled, phase 2 clinical trial. Lancet. 2023 Jan 14;401(10371):131-139. doi: 10.1016/S0140-6736(22)02397-2. Epub 2022 Dec 7.

  PMID: 36495882 DERIVED

MeSH Terms

Conditions

Poliomyelitis

Condition Hierarchy (Ancestors)

Myelitis; Central Nervous System Infections; Infections; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Virus Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Neuroinflammatory Diseases; Neuromuscular Diseases

Study Officials

• K Zaman, PhD FRCP

  International Centre for Diarrhoeal Disease Research, Bangladesh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2020
• First Posted: January 5, 2021
• Study Start: September 21, 2020
• Primary Completion: August 30, 2021
• Study Completion: August 30, 2021
• Last Updated: August 30, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: July 2021

Locations

BA (1)