PoliomyelitisPhase 1nOPV2M4aNCT03430349
Phase 1 Novel Live Attenuated Serotype 2 Oral Polio Vaccine Study in Inactivated Polio Vaccine (IPV) Primed Adults
A Phase 1 study testing Novel OPV2 candidate 1 and Novel OPV2 candidate 2 in people with Poliomyelitis, run by Pierre Van Damme at 1 site in Belgium.
Trial summary
This first-in-human (FIH) phase 1 study is designed to evaluate in contained conditions the safety, immunogenicity, shedding, and genetic stability of two novel oral polio vaccine type 2 (nOPV2) vaccine candidates in IPV-primed adults before testing in a larger adult and adolescent (> 15 y of age) population, and then… Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Poliomyelitis
- What is being tested?
- Novel OPV2 candidate 1 and Novel OPV2 candidate 2
- Type of treatment
- Vaccines, Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteBelgium
- Study dates
- 16 May 2017to 27 Oct 2017
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy male or female, between 18 and 50 years old, extremes included, having received at least 3 doses of IPV in the past (more than 12 months before the start of the study);
- In good physical and mental health as determined on the basis of medical history, laboratory screening tests and general physical and psychological examination;
- Female subjects of childbearing potential must agree to the use of an effective method of birth control throughout the study and up to 3 months after vaccine administration;
- Willing to adhere to the prohibitions and restrictions specified in this protocol;
- Willing to adhere to the restrictions of containment for duration as specified in the protocol;
- Informed Consent Form (ICF) signed voluntarily by the subject before any study-related procedure is performed, indicating that the subject understands the purpose of and procedures required for the study and is willing to participate in the study.
Show all 11Show fewer
- Furthermore, willing to adhere to following restrictions as long as shedding will be observed at the end of the containment period:
- No intention to travel to the Netherlands and to polio endemic countries (updated list will be made available at the start of the study);
- No professional handling of food, catering or food production activities;
- Not having household or professional contact with known immunosuppressed people or people without full polio vaccination (i.e. complete primary infant immunization series), e.g. babysitting;
- No neonatal nursing activities or other professional contact with children under 6 months old;
Who cannot join
- A condition that, in the opinion of the Investigator, could compromise the well being of the subject or course of the study, or prevent the subject from meeting or performing any study requirements;
- Ever having received any OPV in the past;
- Having Crohn's disease or ulcerative colitis or having had major surgery of the gastrointestinal tract involving significant loss or resection of the bowel;
- A known allergy, hypersensitivity, or intolerance to the study vaccine, or to any of its components or to any antibiotics;
- Any confirmed or suspected immunosuppressive or immunodeficiency condition (including human immunodeficiency virus [HIV] infection, hepatitis B and C infections or negative for total serum IgA);
- Chronic administration (i.e., longer than 14 days) of immunosuppressant drugs or other immune-modifying drugs within 6 months prior to the administration of study vaccine or planned use during the study. For instance, for corticosteroids, this means prednisone, or equivalent, ≥ 0.5 mg/kg/day (inhaled and topical steroids are allowed whereas intra-articular and epidural injection/administration of steroids are not allowed);
Show all 14Show fewer
- Presence of contraindications to administration of the study vaccine on Day 0: acute severe febrile illness deemed by the Investigator to be a contraindication for vaccination or persistent diarrhea or vomiting;
- Indications of drug abuse or excessive use of alcohol at Day 0;
- Being pregnant or breastfeeding. Women of childbearing potential will undergo a pregnancy test at Screening (serum) and at Day 0 (urine). Subjects with a positive pregnancy test will be excluded;
- Participation in another clinical study within 28 days prior to entry in this study or receipt of any investigational product (drug or vaccine) other than the study vaccine within 28 days prior to the administration of study vaccine, or planned use during the study period;
- Administration of any vaccine other than the study vaccine within 28 days prior to the administration of study vaccine and during the entire study period;
- Administration of polio vaccine within 12 months before the start of the study;
- Having had a transfusion of any blood product or application of immunoglobulins within the 4 weeks prior to the administration of study vaccine or during the study;
- Subject is an employee of the Investigator or study site, with direct involvement in the proposed study or other studies under the direction of that Investigator or study site, or is a family member of an employee or the Investigator.
Trial locations and contacts
1 site in 1 country.
Belgium1 site
university of Antwerp - centre for the evaluation of vaccination
Wilrijk, Antwerp, 2610
About this study
Official title: A Phase 1, Blinded, Single Center Study to Evaluate the Safety and Immunogenicity of Two Novel Live Attenuated Serotype 2 Oral Poliovirus Vaccines, Derived From a Modified Sabin 2 Infectious cDNA Clone, in Healthy Adults Previously Primed With Inactivated Polio Vaccine (IPV)
This first-in-human (FIH) phase 1 study is designed to evaluate in contained conditions the safety, immunogenicity, shedding, and genetic stability of two novel oral polio vaccine type 2 (nOPV2) vaccine candidates in IPV-primed adults before testing in a larger adult and adolescent (> 15 y of age) population, and then in young children and infants.
Read the detailed description
Two nOPV2 vaccine candidates have been developed as attenuated serotype 2 polioviruses derived from a modified Sabin 2 infectious complementary deoxyribonucleic acid (cDNA) clone. nOPV2 Candidate 1 (S2/cre5/S15domV/rec1/hifi3) and nOPV2 Candidate 2 (S2/S15domV/CpG40) were generated by modifying the Sabin-2 ribonucleic acid (RNA) sequence to improve phenotypic stability and make the strains less prone to reversion to virulence.
Due to the withdrawal of Sabin monovalent oral polio vaccine type 2 (mOPV2) and prohibition of its use from April 2016 onwards, well before the availability of nOPV2 for clinical testing, Phase 4 trials have been conducted with Sabin mOPV2 to provide control data on safety, immunogenicity, against which data for nOPV2 in subsequent Phase I and II studies will be evaluated and compared. The Phase 4 trials of Sabin mOPV2 were designed to parallel the expected design of the Phase 1 and 2 nOPV2 studies with respect to overall design, inclusion of similar study cohorts. As for these reasons head to head comparison of nOPV2 and mOPV2 is not possible, the overall clinical development plan with the Phase I and II studies was designed taking into consideration the unique situation of OPV2 cessation in April 2016, and the global public health need of a vaccine with lower risk of vaccine-associated paralytic poliomyelitis (VAPP) and vaccine-derived type-2 poliovirus (cVDPV2) (VDPV2) for outbreak response in the post-cessation era.
This first-in-human phase 1 study is designed to evaluate in contained conditions the safety, immunogenicity, shedding and genetic stability of both nOPV2 vaccine candidates in IPV-primed adults before testing in a larger adult and adolescent (> 15 y of age) population, and then in young children and infants.
This Phase 1 study will include 30 IPV-only vaccinated adults to be vaccinated with the study vaccines (15 subjects per candidate vaccine) and followed in contained conditions (28 days) to obtain safety, immunogenicity, shedding and genetic stability data relevant to the decision to advance to future studies with testing in un-contained conditions.
Participants were isolated in a purpose-built containment facility named Poliopolis at the University of Antwerp Hospital (Antwerp, Belgium), to minimize the risk of environmental release of the novel OPV2 candidates. Volunteers were enrolled sequentially in two groups, with each group receiving one of the two vaccine candidates, to avoid cross-contamination, after which they were confined to Poliopolis for 28 days, with further monitoring until end of shedding. A final safety follow-up call (for those no longer shedding) or visit (for those still shedding) was made 42 days after vaccine administration.
- Conditions
- Poliomyelitis
- Being tested
- Novel OPV2 candidate 1, Novel OPV2 candidate 2
- Keywords
- IPV-primed, adults, vaccination, containment, shedding, genetic stability, safety, neurovirulence, novel polio vaccine candidates
- Medical subject headings
- Poliomyelitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Novel OPV2 candidate 1Biological
Live-attenuated serotype-2 poliovirus derived from a modified Sabin type-2 infectious cDNA clone and propagated in Vero cells; candidate 1 (S2/cre5/S15domV/rec1/hifi3).
Modifications included the following:
- Changes to the viral nucleotide sequence in part of the 5'-untranslated region to improve the genetic stability of this major attenuating determinant of Sabin type-2 to avoid reversion by single nucleotide changes.
- Two modifications in the polymerase 3D to further improve stability of the attenuation and reduce frequency of recombination events
- Relocation of a key replication element from the 2C coding region to the 5'-untranslated region, to inhibit recombination.
Novel OPV2 candidate 2Biological
Live-attenuated serotype-2 poliovirus derived from a modified Sabin type-2 infectious cDNA clone and propagated in Vero cells; candidate 2 (S2/S15domV/CpG40).
Modifications included the following:
- Changes to the viral nucleotide sequence in part of the 5'-untranslated region to improve the genetic stability of this major attenuating determinant of Sabin type-2 to avoid reversion by single nucleotide changes.
- silent non-coding modifications engineered within the capsid (VP1-4) designed to reduce replicative fitness and, potentially, to improve stability of the attenuated phenotype while also reducing transmission.
| Study group | Role | What they receive |
|---|---|---|
| Novel OPV2 Candidate 1 | Experimental | Participants received one vaccination with novel OPV2 candidate 1 on study Day 0, administered orally as six drops (0.3 mL total; approximately 10⁶ 50% cell culture infectious dose units [CCID50]). Receives: Biological: Novel OPV2 candidate 1 |
| Novel OPV2 Candidate 2 | Experimental | Participants received one vaccination with novel OPV2 candidate 2 on study Day 0, administered orally as six drops (0.3 mL total; approximately 10⁶ CCID50). Receives: Biological: Novel OPV2 candidate 2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Serious Adverse Events and Severe Adverse Events Throughout the Study
Serious adverse events are medical events that resulted in death, were life-threatening, required admission to hospital, or resulted in notable incapacity of the individual. Adverse events were also graded from mild to severe; Severe adverse events are medical events that prevent normal everyday activities or fever > 39°C; this category does not include serious adverse events.
Serious adverse events and severe adverse events include both solicited and unsolicited events. Solicited events comprised signs and symptoms that were reported by the participant using a predefined checklist in a diary card, or a fever, as determined by the participant's measurement of their body temperature, for up to 7 days after vaccination. Unsolicited events comprised other signs and symptoms recorded through the end of the study.
Adverse events were assessed by the investigator for causality as unrelated, unlikely, possibly, or probably related to the vaccination.
Measured: From Day 0 up to 42 days
Percentage of Participants With Viral Shedding
Participants provided stool samples for assessment of viral shedding, defined as the presence of type 2-specific poliovirus ribonucleic acid (RNA) in stools. Samples were analyzed by the US Centers for Disease Control and Prevention (CDC; Atlanta, GA, USA) for the presence of type-2 poliovirus genome using a Sabin multiplex real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay of total nucleic acid extracted from stool suspensions (50% weight to volume in cell culture medium).
Measured: Days 0, 1, 2, 3, 4, 5, 6, 7, 14, 21, and 28
Cell Culture Infective Dose of Shed Virus in Virus-positive Stool Samples
In stool samples that were positive for type-2 poliovirus detected by RT-PCR, infectious virus was measured as 50% cell culture infective dose (CCID₅₀) per gram of stool by use of a modification of the World Health Organization (WHO) cell sensitivity assay.
Measured: Days 1, 2, 3, 4, 5, 6, 7, 14, 21, and 28
Time to Shedding Cessation
The time to cessation of shedding was defined as the time interval between administration of vaccine and the date of the first sample negative for type 2 poliovirus shedding (assessed by RT-PCR) after which the following two consecutive samples were also negative.
Time to cessation of viral shedding was assessed using Kaplan-Meier methods; participants were right-censored if they had not met this endpoint with the last stool sample collected.
Measured: Stool samples were collected from the day of vaccination to Day 28 or until shedding cessation; up to 89 days (novel OPV2 candidate 1) and 48 days (novel OPV candidate 2).
Shedding Index
A combined index of the prevalence, duration, and quantity of viral shedding in all participants.
The viral shedding index was calculated for each participant as the mean of log₁₀(CCID₅₀/g) of samples collected 7, 14, 21, and 28 days after vaccine administration, with the lower limit of quantitation (2.75 log₁₀) as an observed value, and all titers in stool samples with negative shedding results (real-time RT-PCR-negative values) contributing 0 to the mean.
Measured: Days 7, 14, 21, and 28
Secondary outcomes (7)
Number of Participants With Solicited Adverse Events
Adverse events were solicited from the participants by the medical team during the 7 days after vaccination. Solicited events comprised signs and symptoms that were reported with a predefined checklist in a diary card, including headache, fatigue, myalgia, arthralgia, paresthesia, anesthesia, paralysis, nausea, vomiting, diarrhea and abdominal pain, or fever defined as a temperature of 37.5°C or higher.
Adverse events were graded as mild (easily tolerated), moderate (sufficiently discomforting to interfere with normal everyday activities), or severe (preventing normal everyday activities, or temperatures higher than 39.0°C).
Adverse events were assessed by the investigator for causality as unrelated, unlikely, possibly, or probably related to the vaccination.
Measured: Day 0 to Day 7
Number of Participants With Unsolicited Adverse Events
Unsolicited events comprised other signs and symptoms that participants reported through the end of the study. Each unsolicited AE was rated on a 3-point scale of increasing intensity:
- Grade 1: Mild; an AE that was easily tolerated by the subject, causing minimal discomfort and not interfering with everyday activities.
- Grade 2: Moderate; an AE that was sufficiently discomforting to interfere with normal everyday activities.
- Grade 3: Severe; an AE that prevented normal everyday activities.
Each adverse event was assessed by the investigator for causality as unrelated, unlikely, possibly, or probably related to the vaccination.
Measured: From Day 0 up to 42 days
Number of Participants With Clinically Relevant Deviations From Normal Laboratory Evaluations
Clinical laboratory test values were evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 (toxicity grades) or in accordance with the normal ranges of the clinical laboratory (below, within, or above normal range) for parameters for which no toxicity grades were defined.
Clinical chemistry assessments included total bilirubin, glucose, blood urea nitrogen (BUN), creatinine, calcium, inorganic phosphate, potassium, sodium, alanine aminotransferase, aspartate aminotransferase, and C-reactive protein (CRP). Hematology assessments included hemoglobin, hematocrit, red blood cells, and white blood cells with differential.
Measured: Screening, Day 7, Day 14, and Day 28
Anti-Poliovirus Type-2 Neutralizing Antibody Titers
Neutralizing antibodies against poliovirus type 2 were determined using the WHO standard microneutralization assay (WHO EPI GEN 93.9).
Measured: Day 0 and Day 28
Seroprotection Rate
Seroprotection rate was defined as the percentage of participants in each group with anti-type 2-specific poliovirus neutralizing antibodies titers ≥ 1:8.
Measured: Day 0 and Day 28
Seroconversion Rate
Seroconversion rate is defined as the percentage of participants in each group with a change from seronegative to seropositive (poliovirus type-2-specific neutralizing antibody titers ≥ 1:8) or, in participants seropositive at Baseline, an increase in neutralizing antibody titer of at least four-fold from Baseline.
Measured: Day 28
Neurovirulence Assessed by the Average Percent Paralysis in Inoculated Mice
Neurovirulence of shed virus was measured using a modified WHO poliovirus receptor transgenic mouse neurovirulence test (mTgmNVT). The last stool sample provided by each participant that had adequate concentrations of virus for the neurovirulence assay (≥ 4 log₁₀[CCID₅₀/g]) was used in the test. For each stool specimen thirty Tg-PVR21 mice were administered intraspinal inoculations of 4 log₁₀(CCID₅₀) amplified virus. After 14 days the inoculated mice were assessed as either paralyzed or non-paralyzed. For each participant/sample, the percentage of paralyzed mice was calculated. Overall percent paralysis is the average percentage of paralyzed mice over all participants in each group.
Measured: Samples tested were the last post-vaccination sample per participant suitable for analysis; samples used in the analysis ranged from Day 2 to Day 56
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2018
- Study start16 May 2017
- Primary completion30 Sep 2017
- Study completion27 Oct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- 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 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pierre Van Damme
- Sponsor type
- University, hospital or other
- Collaborators
- Bill and Melinda Gates Foundation, Centers for Disease Control and Prevention, PATH, Celerion
- Responsible party
- Sponsor-investigator, Pierre Van Damme, Universiteit Antwerpen
- Investigators
- pierre van damme, MD,PHD, Principal investigator, centre for the evaluation of vaccination
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03430349
- Sponsor's protocol ID
- UAM4a
- Other IDs
- 2017-000908-21, 2017
- Acronym
- nOPV2M4a
- Status last verified
- Jan 2021
- First submitted
- 21 Jan 2018
- Last updated
- 4 Feb 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: there is no such plan for the moment
Publications
Van Damme P, De Coster I, Bandyopadhyay AS, Revets H, Withanage K, De Smedt P, Suykens L, Oberste MS, Weldon WC, Costa-Clemens SA, Clemens R, Modlin J, Weiner AJ, Macadam AJ, Andino R, Kew OM, Konopka-Anstadt JL, Burns CC, Konz J, Wahid R, Gast C. The safety and immunogenicity of two novel live attenuated monovalent (serotype 2) oral poliovirus vaccines in healthy adults: a double-blind, single-centre phase 1 study. Lancet. 2019 Jul 13;394(10193):148-158. doi: 10.1016/S0140-6736(19)31279-6. Epub 2019 Jun 4.
PubMed 31174831
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Blinded, Single Center Study to Evaluate the Safety and Immunogenicity of Two Novel Live Attenuated Serotype 2 Oral Poliovirus Vaccines, Derived From a Modified Sabin 2 Infectious cDNA Clone, in Healthy Adults Previously Primed With Inactivated Polio Vaccine (IPV)
- ClinicalTrials.gov ID
- NCT03430349
- Acronym / sponsor ID
- nOPV2M4a / UAM4a
- Conditions
- Poliomyelitis
- Keywords
- IPV-primed, adults, vaccination, containment, shedding, genetic stability, safety, neurovirulence
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Pierre Van DammeUniversity, hospital or other
- Collaborators
- Bill and Melinda Gates Foundation, Centers for Disease Control and Prevention, PATH, Celerion
- Study start
- 16 May 2017 (actual)
- Primary completion
- 30 Sep 2017 (actual)
- Study completion
- 27 Oct 2017 (actual)
- First posted
- 12 Feb 2018 (actual)
- Results
- Posted 4 Feb 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This first-in-human (FIH) phase 1 study is designed to evaluate in contained conditions the safety, immunogenicity, shedding, and genetic stability of two novel oral polio vaccine type 2 (nOPV2) vaccine candidates in IPV-primed adults before testing in a larger adult and adolescent (> 15 y of age) population, and then in young children and infants.
Detailed description
Two nOPV2 vaccine candidates have been developed as attenuated serotype 2 polioviruses derived from a modified Sabin 2 infectious complementary deoxyribonucleic acid (cDNA) clone. nOPV2 Candidate 1 (S2/cre5/S15domV/rec1/hifi3) and nOPV2 Candidate 2 (S2/S15domV/CpG40) were generated by modifying the Sabin-2 ribonucleic acid (RNA) sequence to improve phenotypic stability and make the strains less prone to reversion to virulence.
Due to the withdrawal of Sabin monovalent oral polio vaccine type 2 (mOPV2) and prohibition of its use from April 2016 onwards, well before the availability of nOPV2 for clinical testing, Phase 4 trials have been conducted with Sabin mOPV2 to provide control data on safety, immunogenicity, against which data for nOPV2 in subsequent Phase I and II studies will be evaluated and compared. The Phase 4 trials of Sabin mOPV2 were designed to parallel the expected design of the Phase 1 and 2 nOPV2 studies with respect to overall design, inclusion of similar study cohorts. As for these reasons head to head comparison of nOPV2 and mOPV2 is not possible, the overall clinical development plan with the Phase I and II studies was designed taking into consideration the unique situation of OPV2 cessation in April 2016, and the global public health need of a vaccine with lower risk of vaccine-associated paralytic poliomyelitis (VAPP) and vaccine-derived type-2 poliovirus (cVDPV2) (VDPV2) for outbreak response in the post-cessation era.
This first-in-human phase 1 study is designed to evaluate in contained conditions the safety, immunogenicity, shedding and genetic stability of both nOPV2 vaccine candidates in IPV-primed adults before testing in a larger adult and adolescent (> 15 y of age) population, and then in young children and infants.
This Phase 1 study will include 30 IPV-only vaccinated adults to be vaccinated with the study vaccines (15 subjects per candidate vaccine) and followed in contained conditions (28 days) to obtain safety, immunogenicity, shedding and genetic stability data relevant to the decision to advance to future studies with testing in un-contained conditions.
Participants were isolated in a purpose-built containment facility named Poliopolis at the University of Antwerp Hospital (Antwerp, Belgium), to minimize the risk of environmental release of the novel OPV2 candidates. Volunteers were enrolled sequentially in two groups, with each group receiving one of the two vaccine candidates, to avoid cross-contamination, after which they were confined to Poliopolis for 28 days, with further monitoring until end of shedding. A final safety follow-up call (for those no longer shedding) or visit (for those still shedding) was made 42 days after vaccine administration.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Novel OPV2 Candidate 1 | Experimental | Biological: Novel OPV2 candidate 1Participants received one vaccination with novel OPV2 candidate 1 on study Day 0, administered orally as six drops (0.3 mL total; approximately 10⁶ 50% cell culture infectious dose units [CCID50]). |
| Novel OPV2 Candidate 2 | Experimental | Biological: Novel OPV2 candidate 2Participants received one vaccination with novel OPV2 candidate 2 on study Day 0, administered orally as six drops (0.3 mL total; approximately 10⁶ CCID50). |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- Healthy male or female, between 18 and 50 years old, extremes included, having received at least 3 doses of IPV in the past (more than 12 months before the start of the study);
- In good physical and mental health as determined on the basis of medical history, laboratory screening tests and general physical and psychological examination;
- Female subjects of childbearing potential must agree to the use of an effective method of birth control throughout the study and up to 3 months after vaccine administration;
- Willing to adhere to the prohibitions and restrictions specified in this protocol;
- Willing to adhere to the restrictions of containment for duration as specified in the protocol;
Key exclusion criteria (14 listed)
- A condition that, in the opinion of the Investigator, could compromise the well being of the subject or course of the study, or prevent the subject from meeting or performing any study requirements;
- Ever having received any OPV in the past;
- Having Crohn's disease or ulcerative colitis or having had major surgery of the gastrointestinal tract involving significant loss or resection of the bowel;
- A known allergy, hypersensitivity, or intolerance to the study vaccine, or to any of its components or to any antibiotics;
- Any confirmed or suspected immunosuppressive or immunodeficiency condition (including human immunodeficiency virus [HIV] infection, hepatitis B and C infections or negative for total serum IgA);
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 OPV2 candidate 1Live-attenuated serotype-2 poliovirus derived from a modified Sabin type-2 infectious cDNA clone and propagated in Vero cells; candidate 1 (S2/cre5/S15domV/rec1/hifi3). Modifications included the following: * Changes to the viral nucleotide sequence in part of the 5'-untranslated region to improve the genetic stability of this major attenuating determinant of Sabin type-2 to avoid reversion by single nucleotide changes. * Two modifications in the polymerase 3D to further improve stability of the attenuation and reduce frequency of recombination events * Relocation of a key replication element from the 2C coding region to the 5'-untranslated region, to inhibit recombination. | Biological | Novel OPV2 Candidate 1 |
| Novel OPV2 candidate 2Live-attenuated serotype-2 poliovirus derived from a modified Sabin type-2 infectious cDNA clone and propagated in Vero cells; candidate 2 (S2/S15domV/CpG40). Modifications included the following: * Changes to the viral nucleotide sequence in part of the 5'-untranslated region to improve the genetic stability of this major attenuating determinant of Sabin type-2 to avoid reversion by single nucleotide changes. * silent non-coding modifications engineered within the capsid (VP1-4) designed to reduce replicative fitness and, potentially, to improve stability of the attenuated phenotype while also reducing transmission. | Biological | Novel OPV2 Candidate 2 |
Primary outcome
Number of Participants With Serious Adverse Events and Severe Adverse Events Throughout the Study
Time frame: From Day 0 up to 42 days
Serious adverse events are medical events that resulted in death, were life-threatening, required admission to hospital, or resulted in notable incapacity of the individual. Adverse events were also graded from mild to severe; Severe adverse events are medical events that prevent normal everyday activities or fever > 39°C; this category does not include serious adverse events. Serious adverse events and severe adverse events include both solicited and unsolicited events. Solicited events comprised signs and symptoms that were reported by the participant using a predefined checklist in a diary card, or a fever, as determined by the participant's measurement of their body temperature, for up to 7 days after vaccination. Unsolicited events comprised other signs and symptoms recorded through the end of the study. Adverse events were assessed by the investigator for causality as unrelated, unlikely, possibly, or probably related to the vaccination.
Percentage of Participants With Viral Shedding
Time frame: Days 0, 1, 2, 3, 4, 5, 6, 7, 14, 21, and 28
Participants provided stool samples for assessment of viral shedding, defined as the presence of type 2-specific poliovirus ribonucleic acid (RNA) in stools. Samples were analyzed by the US Centers for Disease Control and Prevention (CDC; Atlanta, GA, USA) for the presence of type-2 poliovirus genome using a Sabin multiplex real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay of total nucleic acid extracted from stool suspensions (50% weight to volume in cell culture medium).
Cell Culture Infective Dose of Shed Virus in Virus-positive Stool Samples
Time frame: Days 1, 2, 3, 4, 5, 6, 7, 14, 21, and 28
In stool samples that were positive for type-2 poliovirus detected by RT-PCR, infectious virus was measured as 50% cell culture infective dose (CCID₅₀) per gram of stool by use of a modification of the World Health Organization (WHO) cell sensitivity assay.
Time to Shedding Cessation
Time frame: Stool samples were collected from the day of vaccination to Day 28 or until shedding cessation; up to 89 days (novel OPV2 candidate 1) and 48 days (novel OPV candidate 2).
The time to cessation of shedding was defined as the time interval between administration of vaccine and the date of the first sample negative for type 2 poliovirus shedding (assessed by RT-PCR) after which the following two consecutive samples were also negative. Time to cessation of viral shedding was assessed using Kaplan-Meier methods; participants were right-censored if they had not met this endpoint with the last stool sample collected.
Shedding Index
Time frame: Days 7, 14, 21, and 28
A combined index of the prevalence, duration, and quantity of viral shedding in all participants. The viral shedding index was calculated for each participant as the mean of log₁₀(CCID₅₀/g) of samples collected 7, 14, 21, and 28 days after vaccine administration, with the lower limit of quantitation (2.75 log₁₀) as an observed value, and all titers in stool samples with negative shedding results (real-time RT-PCR-negative values) contributing 0 to the mean.
7 secondary outcomes
Number of Participants With Solicited Adverse Events
Time frame: Day 0 to Day 7
Number of Participants With Unsolicited Adverse Events
Time frame: From Day 0 up to 42 days
Number of Participants With Clinically Relevant Deviations From Normal Laboratory Evaluations
Time frame: Screening, Day 7, Day 14, and Day 28
Anti-Poliovirus Type-2 Neutralizing Antibody Titers
Time frame: Day 0 and Day 28
Seroprotection Rate
Time frame: Day 0 and Day 28
Seroconversion Rate
Time frame: Day 28
Neurovirulence Assessed by the Average Percent Paralysis in Inoculated Mice
Time frame: Samples tested were the last post-vaccination sample per participant suitable for analysis; samples used in the analysis ranged from Day 2 to Day 56
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31174831Van Damme P, De Coster I, Bandyopadhyay AS, Revets H, Withanage K, De Smedt P, Suykens L, Oberste MS, Weldon WC, Costa-Clemens SA, Clemens R, Modlin J, Weiner AJ, Macadam AJ, Andino R, Kew OM, Konopka-Anstadt JL, Burns CC, Konz J, Wahid R, Gast C. The safety and immunogenicity of two novel live attenuated monovalent (serotype 2) oral poliovirus vaccines in healthy adults: a double-blind, single-centre phase 1 study. Lancet. 2019 Jul 13;394(10193):148-158. doi: 10.1016/S0140-6736(19)31279-6. Epub 2019 Jun 4.
- Individual participant dataSharing planned: No. there is no such plan for the moment
Related trials for Poliomyelitis
Active, not recruiting
Effects of Whole-body Electrical Muscle Stimulation Exercise on Adults With Neuromuscular Disease
Neuromuscular Diseases (NMD), Amyotrophic Lateral Sclerosis
RecruitingPhase 1/2
A Phase I/II Clinical Trial of the Diphtheria, Tetanus, Acellular Component Pertussis and Sabin Inactivated Poliomyelitis Vaccine Adsorbed
Diphtheria, Pertussis
Not yet recruitingPhase 1/2
Safety and Immunogenicity of a Combined Diphtheria, Tetanus, Whole Cell Pertussis, Hepatitis B, Recombinant Poliomyelitis and Haemophilus Influenzae Type b (Hib) Vaccine (SIIPL DTwP-HepB-rPV-Hib)
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.
pierre van damme, MD,PHD principal investigator
centre for the evaluation of vaccination
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Novel OPV2 candidate 1 and Novel OPV2 candidate 2 in people with Poliomyelitis, run by Pierre Van Damme at 1 site in Belgium.
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 11 inclusion and 14 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 4 Feb 2021. 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 Belgium. 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Feb 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With Serious Adverse Events and Severe Adverse Events Throughout the Study (time frame: From Day 0 up to 42 days). The study lists 5 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 NCT03430349, 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 4 Feb 2021.