A Phase 2 Study to Evaluate the Safety and Immunogenicity of Two Oral Poliovirus Vaccine Candidates
NCT ID: NCT04544787
Last Updated: 2021-10-15
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE2
250 participants
INTERVENTIONAL
2018-10-22
2019-05-08
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Due to the withdrawal of Sabin monovalent oral polio vaccine type 2 and prohibition of its use from April 2016 onward, well before the availability of nOPV2 for clinical testing, a head to head comparison of nOPV2 and mOPV2 is not possible. For these reasons, 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.
This study is designed to evaluate the safety and immunogenicity of two novel type 2 OPV candidates in adults before testing in young children and then infants. The study will include both OPV-vaccinated and IPV-vaccinated adults to provide safety and immunogenicity data relevant to the decision to advance to future studies with testing in children who have not been exposed to OPV2. The primary objectives of the study include the general safety and immunogenicity of the two candidate vaccines, primarily based on comparison with historical data obtained in a Phase 4 study of Sabin mOPV2 for OPV-vaccinated subjects, in order to establish non-inferior immunogenicity and acceptable safety profile. Assessment of the general safety of the 2 candidate vaccines in IPV-only vaccinated participants will be based on comparison with data from a placebo group.
The phase 4 control study (UAM1) used for the comparison in this study is registered with EudraCT (2015-003325-33). Participants were healthy adults aged 18-50 years with documented history of at least three polio vaccinations, including OPV, and were randomly assigned to either one dose or two doses of monovalent OPV2. Between January and March 2016, 100 volunteers were enrolled and randomly assigned to receive one or two doses of monovalent OPV2 (n=50 in each group).
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
SEQUENTIAL
OPV-vaccinated adults:
* 1 dose of nOPV2 candidate 1 (Group 1);
* 2 doses of nOPV2 candidate 1 (Group 2);
* 1 dose of nOPV2 candidate 2 (Group 3);
* 2 doses of nOPV2 candidate 2 (Group 4);
IPV-only vaccinated adults:
* 2 doses of nOPV2 candidate 1 (Group 5);
* 2 doses of nOPV2 candidate 2 (Group 6);
* 2 doses of placebo (Group 7).
The first 100 OPV-vaccinated participants will be randomly assigned 1:1 to Groups 3 (1 dose) and 4 (2 doses) to receive nOPV2-c2. The second 100 OPV-vaccinated participants will be randomly assigned 1:1 to Groups 1 (1 dose) and 2 (2 doses) to receive nOPV2-c1. IPV-vaccinated adults will be enrolled in parallel and randomly assigned 2:1 to Group 6 (2 doses of nOPV2-c2) or Group 7 (2 doses of placebo), until Group 6 enrollment is complete, when 2:1 randomization will be continued for Group 5 (2 doses of nOPV2-c1) and Group 7 (2 doses of placebo).
PREVENTION
QUADRUPLE
For the study duration participants and blinded study staff responsible for safety evaluation of IPV participants will not have any information of what has been administered. As the placebo can be distinguished from the vaccine candidates in packaging and color, reception of the vaccines, dose preparation and administration will be done by a team of unblinded study personnel. Appropriate measures will be taken at the site to ensure blinding of subjects and blinded team for the duration of the study.
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Group 1: One Dose of Novel OPV2 Candidate 1
Participants previously vaccinated with oral polio vaccine (OPV) received one dose of novel OPV2 candidate 1 on Day 0, administered orally as six drops (0.3 mL total; approximately 10⁶ 50% cell culture infectious dose units \[CCID50\]).
Novel OPV2 candidate 1
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.
Group 2: Two Doses of Novel OPV2 Candidate 1
Participants previously vaccinated with OPV received two doses of novel OPV2 candidate 1 28 days apart (Day 0 and Day 28), administered orally as six drops (0.3 mL total; approximately 10⁶ CCID50).
Novel OPV2 candidate 1
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.
Group 3: One Dose of Novel OPV2 Candidate 2
Participants previously vaccinated with OPV received one dose of novel OPV2 candidate 2 on study Day 0, administered orally as six drops (0.3 mL total; approximately 10⁶ CCID50).
Novel OPV2 candidate 2
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.
Group 4: Two Doses of Novel OPV2 Candidate 2
Participants previously vaccinated OPV received two doses novel OPV2 candidate 2 28 days apart (Day 0 and Day 28), administered orally as six drops (0.3 mL total; approximately 10⁶ CCID50).
Novel OPV2 candidate 2
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.
Group 5: Two Doses of Novel OPV2 Candidate 1
Participants previously vaccinated with inactivated polio vaccine (IPV) received two doses of novel OPV2 candidate 1 28 days apart (Day 0 and Day 28), administered orally as six drops (0.3 mL total; approximately 10⁶ CCID50).
Novel OPV2 candidate 1
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.
Group 6: Two Doses of Novel OPV2 Candidate 2
Participants previously vaccinated with IPV received two doses of novel OPV2 candidate 2 28 days apart (Day 0 and Day 28), administered orally as six drops (0.3 mL total; approximately 10⁶ CCID50).
Novel OPV2 candidate 2
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.
Group 7: Two Doses of Placebo
Participants previously vaccinated with IPV received two doses of placebo 28 days apart (Day 0 and Day 28), administered orally as six drops (0.3 mL total).
Placebo
sugar syrup, propylene glycol (Sirupus simplex, Propylenglycolum, European Pharmacopoeia)
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Novel OPV2 candidate 1
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 2
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.
Placebo
sugar syrup, propylene glycol (Sirupus simplex, Propylenglycolum, European Pharmacopoeia)
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
2. For Groups 5, 6 and 7: healthy males or females, from 18 to 50 years of age inclusive, having previously received at least 3 doses of IPV more than 12 months before the start of the study;
3. Having residence in Belgium;
4. In good physical and mental health as determined on the basis of medical history and general physical examination performed at Day 0;
5. 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 last vaccine dose;
6. Willing to adhere to the prohibitions and restrictions specified in this protocol;
7. Informed Consent Form (ICF) and Code of Conduct signed voluntarily by the subject before any study-related procedure is performed, indicating that the subject understands the purpose of any procedures required for the study and is willing to participate in the study.
Exclusion Criteria
2. For Groups 5, 6 and 7: ever having received any OPV in the past;
3. Any travel to polio endemic countries or countries with evidence of recent (within last 6 months) wild or vaccine-derived poliovirus circulation during the total duration of the study;
4. Professional handling of food, catering or food production activities during the total duration of the study;
5. Having Crohn's disease or ulcerative colitis or having had major surgery of the gastrointestinal tract involving significant loss or resection of the bowel;
6. A known allergy, hypersensitivity, or intolerance to the study vaccine or the placebo, or to any of their components or to any antibiotics;
7. Any confirmed or suspected immunosuppressive or immunodeficiency condition (including human immunodeficiency virus \[HIV\] infection, hepatitis B or C infections or total serum immunoglobulin A \[IgA\] level below laboratory lower limit of normal \[LLN\]);
8. Will have household or professional contact with known immunosuppressed people or people without full polio vaccination (i.e. complete primary infant immunization series), e.g. babysitting during the total duration of the study;
9. Neonatal nurses or others having professional contact with children under 6 months of age during the total duration of the study;
10. Chronic administration (i.e., longer than 14 days) of immunosuppressant drugs or other immune-modifying drugs within 6 months prior to the first vaccine dose 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);
11. 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;
12. Indications of drug abuse or excessive use of alcohol at Day 0 (males: \> 21 units/week; females \> 14 units/week);
13. Being pregnant or breastfeeding. Women of childbearing potential will undergo a urine pregnancy test at each vaccination visit. Subjects with a positive pregnancy test will be excluded;
14. 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 first administration of study vaccine, or planned use during the study period;
15. Administration of any vaccine other than the study vaccine within 28 days prior to the first dose of study vaccine and during the entire study period;
16. Administration of any polio vaccine within 12 months before the start of the study;
17. Having had a transfusion of any blood product or application of immunoglobulins within the 4 weeks prior to the first administration of study vaccine or during the study;
18. 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, or was a study subject in the historical control studies UAM1 or UAT1 or in the study UAM4a (NCT03430349);
19. Having a family or household member participating in the study CVIA 065 (NCT04232943) or being a study subject in the study CVIA 065.
18 Years
50 Years
ALL
Yes
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Bill and Melinda Gates Foundation
OTHER
Centers for Disease Control and Prevention
FED
PATH
OTHER
Celerion
INDUSTRY
Pierre Van Damme
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Pierre Van Damme
Full Professor
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Pierre Van Damme, Prof. MD
Role: PRINCIPAL_INVESTIGATOR
Centre for the evaluation of vaccination
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Centre for the Evaluation of Vaccination, Vaccine & Infectious Disease Institute, University of Antwerp
Wilrijk, Antwerp, Belgium
CEVAC, Center for Vaccinology, Ghent University Hospital
Ghent, , Belgium
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
De Coster I, Leroux-Roels I, Bandyopadhyay AS, Gast C, Withanage K, Steenackers K, De Smedt P, Aerssens A, Leroux-Roels G, Oberste MS, Konopka-Anstadt JL, Weldon WC, Fix A, Konz J, Wahid R, Modlin J, Clemens R, Costa Clemens SA, Bachtiar NS, Van Damme P. Safety and immunogenicity of two novel type 2 oral poliovirus vaccine candidates compared with a monovalent type 2 oral poliovirus vaccine in healthy adults: two clinical trials. Lancet. 2021 Jan 2;397(10268):39-50. doi: 10.1016/S0140-6736(20)32541-1. Epub 2020 Dec 9.
Thompson KM, Kalkowska DA, Kidd SE, Burns CC, Badizadegan K. Trade-offs of different poliovirus vaccine options for outbreak response in the United States and other countries that only use inactivated poliovirus vaccine (IPV) in routine immunization. Vaccine. 2024 Feb 6;42(4):819-827. doi: 10.1016/j.vaccine.2023.12.081. Epub 2024 Jan 12.
Provided Documents
Download supplemental materials such as informed consent forms, study protocols, or participant manuals.
Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
2018-001684-22
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
UAM4
Identifier Type: -
Identifier Source: org_study_id