Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Clinical Trial of Novel OPV2 Vaccine

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04693286
Recruitment Status : Recruiting
First Posted : January 5, 2021
Last Update Posted : October 1, 2021
Sponsor:
Collaborators:
Bill and Melinda Gates Foundation
Centers for Disease Control and Prevention
PATH
World Health Organization
PT Bio Farma
Information provided by (Responsible Party):
International Centre for Diarrhoeal Disease Research, Bangladesh

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 For this reason tOPV vaccine was withdrawn globally in April 2016 and switched to bOPV.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


Condition or disease Intervention/treatment Phase
Poliomyelitis Biological: novel oral polio type 2 vaccine (nOPV2) Other: Placebo Phase 2

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 330 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Phase II Clinical Trial to Evaluate the Safety and Immunogenicity of Novel Oral Polio Type 2 Vaccine Candidate in Healthy Newborns in Bangladesh
Actual Study Start Date : September 21, 2020
Estimated Primary Completion Date : December 30, 2021
Estimated Study Completion Date : December 30, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Vaccine candidate arm
In this arm, participants will get nOPV2 vaccine candidate 1
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.

Placebo Comparator: Placebo arm
In this arm, participants will get inactive substance like sucrose in BME media and buffer.
Other: Placebo
Placebo contains no active ingradients, only sucrose in buffer




Primary Outcome Measures :
  1. Safety of nOPV2 vaccine [ Time Frame: Upto 3 months ]
    • 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

  2. Immunogenecity of nOPV2 vaccine , will be assessed as poliovirus type-2-specific serum neutralising antibodies [ Time Frame: 4 weeks ]
    Proportion of participants showing seroconversion and seroprotection will be calculated and reported

  3. 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 [ Time Frame: 12 weeks ]
    Vaccine poliovirus shedding in the study participants stool will be assessed by real-time RT-PCR method.


Secondary Outcome Measures :
  1. Genetic assay and Neurovirulance test to assess genetic stability by demonstrating the retention of key genetic regions engineered in the vaccine candidate [ Time Frame: 4 weeks ]
    WHO poliovirus receptor transgenic mouse (Tg-PVR21) neurovirulence test will be used. Deep sequencing will be performed on the cell culture-amplified virus and on viral RNA isolated from participants



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   up to 3 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04693286


Contacts
Layout table for location contacts
Contact: K Zaman, PhD FRCP +880-2-9827001-10 ext 3806 kzaman@icddrb.org
Contact: Masuma Hoque, MBBS MPH 01836976300 masuma.hoque@icddrb.org

Locations
Layout table for location information
Bangladesh
: International Centre for Diarrhoeal Disease Research, Bangladesh Recruiting
Dhaka, Bangladesh, 1212
Contact: masuma hoque, MBBS, MPH    01836976300    masuma.hoque@icddrb.org   
Contact: Arif Reza, MBBS    01712276260      
Sponsors and Collaborators
International Centre for Diarrhoeal Disease Research, Bangladesh
Bill and Melinda Gates Foundation
Centers for Disease Control and Prevention
PATH
World Health Organization
PT Bio Farma
Investigators
Layout table for investigator information
Principal Investigator: K Zaman, PhD FRCP International Centre for Diarrhoeal Disease Research, Bangladesh
Layout table for additonal information
Responsible Party: International Centre for Diarrhoeal Disease Research, Bangladesh
ClinicalTrials.gov Identifier: NCT04693286    
Other Study ID Numbers: PR-20001
First Posted: January 5, 2021    Key Record Dates
Last Update Posted: October 1, 2021
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD will be shared with BMGF, PATH, CDC, WHO
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: July 2021

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by International Centre for Diarrhoeal Disease Research, Bangladesh:
Safety
Immunogenecity
nOPV2
Newborn
Bangladesh
Additional relevant MeSH terms:
Layout table for MeSH terms
Poliomyelitis
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
Neuromuscular Diseases