A Phase 2 Study to Evaluate the Safety and Immunogenicity of Two Oral Poliovirus Vaccine Candidates
Condition: Poliomyelitis
MeSH terms: Poliomyelitis
Intervention: Novel OPV2 candidate 1; Novel OPV2 candidate 2; Placebo
Intervention description: 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.; 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.; sugar syrup, propylene glycol (Sirupus simplex, Propylenglycolum, European Pharmacopoeia)
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention model description: In this partial-blind study participants will be randomized into one of the following groups:
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).
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: All OPV-vaccinated participants will receive one of the nOPV2 candidates candidates in a single blind manner and all IPV- vaccinated participants will receive one of the nOPV2 candidates or placebo in a double-blinded manner.
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.
Enrollment: 250.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: IPV-primed; adults; vaccination; shedding; genetic stability; safety; neurovirulence; novel polio vaccine candidates

Summary:

      This study is designed to evaluate the safety and immunogenicity of two novel type 2 oral
      poliovirus vaccine (nOPV2) candidates (nOPV2 candidate 1 and nOPV2 candidate 2) in adults.
      The primary objectives of the study include the general safety and immunogenicity of the two
      candidate vaccines in healthy volunteers previously vaccinated with Sabin monovalent OPV or
      inactivated polio vaccine (IPV) only.
    

Eligibility criteria:

        Inclusion Criteria:

          1. For Groups 1, 2, 3 and 4: healthy males or females, from 18 to 50 years of age
             inclusive, having previously received at least 3 doses of OPV more than 12 months
             before the start of the study;

          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:

          1. 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;

          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.