PoliomyelitisPhase 2NCT04693286
Clinical Trial of Novel OPV2 Vaccine
A Phase 2 study testing novel oral polio type 2 vaccine (nOPV2) in people with Poliomyelitis, run by International Centre for Diarrhoeal Disease Research, Bangladesh at 1 site in Bangladesh.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 hour to 3 daysHealthy volunteers can take part
- Conditions the study is for
- Poliomyelitis
- What is being tested?
- novel oral polio type 2 vaccine (nOPV2)
- Type of treatment
- Vaccines, Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 330 participants
- Where
- 1 siteBangladesh
- Study dates
- 21 Sep 2020to 30 Aug 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 hour to 3 days
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- 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.
Who cannot join
- 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).
Trial locations and contacts
1 site in 1 country.
Bangladesh1 site
: International Centre for Diarrhoeal Disease Research, Bangladesh
Dhaka, 1212
About this study
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
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
Read more
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
Read the detailed description
Burden: Oral Polio Vaccine (OPV) contains attenuated (weakened) polioviruses. Though OPV is safe and effective, it can mutate and reacquire neurovirulence in rare circumstances. This can result in vaccine-associated paralytic polio (VAPP) and circulating vaccine-derived polioviruses (cVDPVs) on rare occasions. Use of tOPV, therefore, had the risk of generating VAPP and seeding new type 2 circulating vaccine-derived polioviruses (cVDPV2), even though the wild type 2 virus was eradicated in September 2015. For this reason tOPV vaccine was withdrawn globally in April 2016 and switched to the bivalent oral poliovirus vaccine (bOPV). Circulating vaccine-derived type-2 poliovirus (cVDPV2) outbreaks have occurred in sixteen countries after cassation of OPV2. Using stockpiled mOPV2 to respond to this situation risks propagating new cVDPVs and this phenomenon has already been observed in multiple geographies following the switch. Inactivated polio vaccine (IPV) induces only limited intestinal mucosal immunity and is not effective to interrupt fecal-oral route transmission in settings of poor hygiene and sanitation. Therefore, development of novel oral polio vaccine/s with enhanced genetic stability and lower risk of reversion to neurovirulence compared to current Sabin 2 strains is a major priority of the global polio eradication Program.
Knowledge gap: The current clinical development plan outlines studies through Phase II development with the nOPV2 candidate strains being tested in adult, toddler, and infant populations who have received prior dose/s of OPV and/or IPV. No study has been conducted in truly naive newborns with no prior receipt of any polio vaccines to strengthen the clinical evidence in favour of utilizing these novel OPV strains.
Relevance: Existing Sabin type 2 polio virus vaccines can mutate in to pathogenic virus and become neurovirulent, causing VAPP and cVDVP. So novel type 2 polio virus candidate vaccines is an urgent need especially for outbreak situations. The nOPV2 strains are intended for use as safer alternatives to mOPV2 vaccines for outbreak response. Data from this proposed study result will further strengthen the clinical evidence base to deploy novel, genetically stable OPV strains to reduce the risk of generating cVDPV and VAPP. The study will generate data on novel OPV2 candidates for pre-licensure use in outbreak scenarios and for eventual full licensure and WHO Prequalification.
Hypothesis : Vaccinating healthy newborns with novel type 2 polio virus candidate vaccines (nOPV2) is safe and can induce a putatively protective immune response.
Objectives:
Primary Objectives:
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 newborns.
Immunogenicity:
- To evaluate the immune response (measured by seroconversion rate) 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 the rate of fecal viral shedding (as determined by real-time RT-PCR) at fixed time points following one and two doses of nOPV2 vaccine candidate 1 in newborns.
- To assess the duration of fecal viral shedding (as determined by real-time RT-PCR) at fixed time points following one and two doses of nOPV2 vaccine candidate 1 in newborns.
- To assess the extent of fecal viral shedding ( the quantity of nOPV2 virus shedding, measured asCCID50 per g of stool) 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.
Methods:
The study is a Phase II clinical trial which will be conducted in rural Bangladesh at Matlab. The total enrolment target for the clinical trial is 330 , with 220 in nOPV2 candidate 1 arm and 110 in placebo arm. All participants will be randomized (in block randomization of variable length) 2:1 ratio to nOPV2 vaccine candidate C1(2 drops) and placebo group (2 drops). All eligible healthy newborn participants will be vaccinated orally at birth and at 4 weeks of age with C1 (105.0± 0.5 CCID50, 2 drops) or placebo (2 drops) of age followed by fIPV + bOPV at week 8, bOPV at week 12 and fIPV + bOPV at week 16 and other vaccines according to EPI schedule in Bangladesh.
In order to record any immediate reaction participants will be observed for 30 minutes following each dose of vaccination. Study staff will visit homes of the participants daily for 7 days to collect systemic solicited adverse events after study vaccination using electronic dairy cards. Unsolicited adverse events, adverse events of special interest and serious adverse events will be collected throughout the entire study period by weekly home visit. Mothers of the participant will be provided a telephone number to communicate with the investigator for any adverse or serious adverse events.
Three blood samples each of 1 ml, will be collected to measure the immune response of nOPV vaccine candidate 1: the first pre-vaccine blood sample on the day of first dose nOPV2 vaccine candidate 1 /placebo (at birth), second blood sample at 4 weeks before second dose nOPV2 vaccine candidate 1 /placebo and the third blood sample will be collected at 8 weeks before giving fIPV + bOPV vaccine.
Mothers of enrolled participants will be requested to collect about 8 grams (about the size of one adult thumb) of stool from participants to assess viral sheddings. A total of seven stool samples will be collected: the first pre-vaccine sample will be collected on the day of first dose nOPV2 vaccine candidate 1 /placebo (at birth), second sample at week 2, third sample at week 4 before second dose nOPV2 vaccine candidate 1 /placebo, fourth stool sample at week 6, fifth stool at week 8 before giving fIPV + bOPV vaccine, sixth stool sample at week 10 and seventh sample at week 12 of age to assess viral shedding.
Outcome measures/variables:
Safety
- 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
Immunogenicity
- Seroconversion rate as measured by microneutralization assay (MN) for OPV Type 2
- Seroprotection rate as measured as seropositivity by MN for OPV Type 2
- Geometric mean and median titers as measured by MN for OPV Type 2
Viral Shedding
- Rate of fecal viral shedding by real-time RT-PCR
- Duration of fecal viral shedding by real-time RT-PCR
- Extent of fecal viral shedding ( the quantity of nOPV2 virus shedding, measured as CCID50 per g of stool) at fixed time points following different dose schedule.
Genetic stability
- Genetic deep sequencing assay and neurovirulence test through transgenic mice NV assays from a subset of participants stools samples.
- Conditions
- Poliomyelitis
- Being tested
- novel oral polio type 2 vaccine (nOPV2), Placebo
- Keywords
- Safety, Immunogenecity, nOPV2, Newborn, Bangladesh
- Medical subject headings
- Poliomyelitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
PlaceboOther
Placebo contains no active ingradients, only sucrose in buffer
| Study group | Role | What they receive |
|---|---|---|
| Vaccine candidate arm | Active comparator | In this arm, participants will get nOPV2 vaccine candidate 1 Receives: 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. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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.
Measured: 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
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
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jan 2021
- Study start21 Sep 2020
- Primary completion30 Aug 2021
- Study completion30 Aug 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PoliomyelitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 330 participants (actual)
Sponsor and investigators
- Lead sponsor
- International Centre for Diarrhoeal Disease Research, Bangladesh
- Sponsor type
- University, hospital or other
- Collaborators
- Bill and Melinda Gates Foundation, Centers for Disease Control and Prevention, PATH, World Health Organization, PT Bio Farma
- Responsible party
- Sponsor
- Investigators
- K Zaman, PhD FRCP, Principal investigator, International Centre for Diarrhoeal Disease Research, Bangladesh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04693286
- Sponsor's protocol ID
- PR-20001
- Status last verified
- Feb 2022
- First submitted
- 14 Dec 2020
- Last updated
- 30 Aug 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD will be shared with BMGF, PATH, CDC, WHO
Publications
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.
PubMed 36495882
Study at a glance
From the registry record, last updated by the sponsor on 30 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04693286
- Acronym / sponsor ID
- PR-20001
- Conditions
- Poliomyelitis
- Keywords
- Safety, Immunogenecity, nOPV2, Newborn, Bangladesh
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 330 participants (actual)
- Lead sponsor
- International Centre for Diarrhoeal Disease Research, BangladeshUniversity, hospital or other
- Collaborators
- Bill and Melinda Gates Foundation, Centers for Disease Control and Prevention, PATH, World Health Organization, PT Bio Farma
- Study start
- 21 Sep 2020 (actual)
- Primary completion
- 30 Aug 2021 (actual)
- Study completion
- 30 Aug 2021 (actual)
- First posted
- 5 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
Burden: Oral Polio Vaccine (OPV) contains attenuated (weakened) polioviruses. Though OPV is safe and effective, it can mutate and reacquire neurovirulence in rare circumstances. This can result in vaccine-associated paralytic polio (VAPP) and circulating vaccine-derived polioviruses (cVDPVs) on rare occasions. Use of tOPV, therefore, had the risk of generating VAPP and seeding new type 2 circulating vaccine-derived polioviruses (cVDPV2), even though the wild type 2 virus was eradicated in September 2015. For this reason tOPV vaccine was withdrawn globally in April 2016 and switched to the bivalent oral poliovirus vaccine (bOPV). Circulating vaccine-derived type-2 poliovirus (cVDPV2) outbreaks have occurred in sixteen countries after cassation of OPV2. Using stockpiled mOPV2 to respond to this situation risks propagating new cVDPVs and this phenomenon has already been observed in multiple geographies following the switch. Inactivated polio vaccine (IPV) induces only limited intestinal mucosal immunity and is not effective to interrupt fecal-oral route transmission in settings of poor hygiene and sanitation. Therefore, development of novel oral polio vaccine/s with enhanced genetic stability and lower risk of reversion to neurovirulence compared to current Sabin 2 strains is a major priority of the global polio eradication Program.
Knowledge gap: The current clinical development plan outlines studies through Phase II development with the nOPV2 candidate strains being tested in adult, toddler, and infant populations who have received prior dose/s of OPV and/or IPV. No study has been conducted in truly naive newborns with no prior receipt of any polio vaccines to strengthen the clinical evidence in favour of utilizing these novel OPV strains.
Relevance: Existing Sabin type 2 polio virus vaccines can mutate in to pathogenic virus and become neurovirulent, causing VAPP and cVDVP. So novel type 2 polio virus candidate vaccines is an urgent need especially for outbreak situations. The nOPV2 strains are intended for use as safer alternatives to mOPV2 vaccines for outbreak response. Data from this proposed study result will further strengthen the clinical evidence base to deploy novel, genetically stable OPV strains to reduce the risk of generating cVDPV and VAPP. The study will generate data on novel OPV2 candidates for pre-licensure use in outbreak scenarios and for eventual full licensure and WHO Prequalification.
Hypothesis : Vaccinating healthy newborns with novel type 2 polio virus candidate vaccines (nOPV2) is safe and can induce a putatively protective immune response.
Objectives:
Primary Objectives:
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 newborns.
Immunogenicity:
- To evaluate the immune response (measured by seroconversion rate) 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 the rate of fecal viral shedding (as determined by real-time RT-PCR) at fixed time points following one and two doses of nOPV2 vaccine candidate 1 in newborns.
- To assess the duration of fecal viral shedding (as determined by real-time RT-PCR) at fixed time points following one and two doses of nOPV2 vaccine candidate 1 in newborns.
- To assess the extent of fecal viral shedding ( the quantity of nOPV2 virus shedding, measured asCCID50 per g of stool) 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.
Methods:
The study is a Phase II clinical trial which will be conducted in rural Bangladesh at Matlab. The total enrolment target for the clinical trial is 330 , with 220 in nOPV2 candidate 1 arm and 110 in placebo arm. All participants will be randomized (in block randomization of variable length) 2:1 ratio to nOPV2 vaccine candidate C1(2 drops) and placebo group (2 drops). All eligible healthy newborn participants will be vaccinated orally at birth and at 4 weeks of age with C1 (105.0± 0.5 CCID50, 2 drops) or placebo (2 drops) of age followed by fIPV + bOPV at week 8, bOPV at week 12 and fIPV + bOPV at week 16 and other vaccines according to EPI schedule in Bangladesh.
In order to record any immediate reaction participants will be observed for 30 minutes following each dose of vaccination. Study staff will visit homes of the participants daily for 7 days to collect systemic solicited adverse events after study vaccination using electronic dairy cards. Unsolicited adverse events, adverse events of special interest and serious adverse events will be collected throughout the entire study period by weekly home visit. Mothers of the participant will be provided a telephone number to communicate with the investigator for any adverse or serious adverse events.
Three blood samples each of 1 ml, will be collected to measure the immune response of nOPV vaccine candidate 1: the first pre-vaccine blood sample on the day of first dose nOPV2 vaccine candidate 1 /placebo (at birth), second blood sample at 4 weeks before second dose nOPV2 vaccine candidate 1 /placebo and the third blood sample will be collected at 8 weeks before giving fIPV + bOPV vaccine.
Mothers of enrolled participants will be requested to collect about 8 grams (about the size of one adult thumb) of stool from participants to assess viral sheddings. A total of seven stool samples will be collected: the first pre-vaccine sample will be collected on the day of first dose nOPV2 vaccine candidate 1 /placebo (at birth), second sample at week 2, third sample at week 4 before second dose nOPV2 vaccine candidate 1 /placebo, fourth stool sample at week 6, fifth stool at week 8 before giving fIPV + bOPV vaccine, sixth stool sample at week 10 and seventh sample at week 12 of age to assess viral shedding.
Outcome measures/variables:
Safety
- 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
Immunogenicity
- Seroconversion rate as measured by microneutralization assay (MN) for OPV Type 2
- Seroprotection rate as measured as seropositivity by MN for OPV Type 2
- Geometric mean and median titers as measured by MN for OPV Type 2
Viral Shedding
- Rate of fecal viral shedding by real-time RT-PCR
- Duration of fecal viral shedding by real-time RT-PCR
- Extent of fecal viral shedding ( the quantity of nOPV2 virus shedding, measured as CCID50 per g of stool) at fixed time points following different dose schedule.
Genetic stability
- Genetic deep sequencing assay and neurovirulence test through transgenic mice NV assays from a subset of participants stools samples.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vaccine candidate arm | Active comparator | Biological: novel oral polio type 2 vaccine (nOPV2)In this arm, participants will get nOPV2 vaccine candidate 1 |
| Placebo arm | Placebo comparator | Other: PlaceboIn this arm, participants will get inactive substance like sucrose in BME media and buffer. |
Who may qualify
- Ages
- 1 hour to 3 days
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Biological | Vaccine candidate arm |
| PlaceboPlacebo contains no active ingradients, only sucrose in buffer | Other | Placebo arm |
Primary outcome
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
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
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.
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Aug 2022.
- Derived from this study: PubMed 36495882Zaman 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.
- Individual participant dataSharing planned: Yes. IPD will be shared with BMGF, PATH, CDC, WHO
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Diptheria Immunization, Tetanus Immunization
RecruitingPhase 1
Safety and Immunogenicity of a Recombinant Poliomyelitis Vaccine (rPV) in Comparison With IPOL Vaccine in Healthy Adults
Polio Immunity
Active, not recruiting
Effects of Virtual Walking on Chronic Pain and Psychological Distress for Individuals With Severe Mobility Impairment
Severe Mobility Impairment, Spinal Cord Injuries (SCI)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
K Zaman, PhD FRCP principal investigator
International Centre for Diarrhoeal Disease Research, Bangladesh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing novel oral polio type 2 vaccine (nOPV2) in people with Poliomyelitis, run by International Centre for Diarrhoeal Disease Research, Bangladesh at 1 site in Bangladesh.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Bangladesh. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of nOPV2 vaccine (time frame: Upto 3 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04693286, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Aug 2022.