Phase 1 Novel Live Attenuated Serotype 2 Oral Polio Vaccine Study in Inactivated Polio Vaccine (IPV) Primed Adults
Condition: Poliomyelitis
MeSH terms: Poliomyelitis
Intervention: Novel OPV2 candidate 1; Novel OPV2 candidate 2
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.
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking description: the study will be conducted with each candidate vaccine sequentially. After randomization of the first participant of Group 1 the next 14 participants will all be enrolled in the same Group and receive the same nOPV2 candidate and the next 15 participants will be enrolled in the other Group and receive the corresponding nOPV2 candidate. Prior to the start of the study the clinical research organization (CRO) will provide the site with 2 randomization envelopes for the first subject. By randomly choosing 1 of the envelopes first subject will be dedicated to a certain nOPV2 candidate and this will determine the allocation of the next 14 subjects to the same Group.
Study staff will be blinded in the same way and will be blinded for individual shedding results of the participants of a Group until end of containment of this Group.
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: IPV-primed; adults; vaccination; containment; shedding; genetic stability; safety; neurovirulence; novel polio vaccine candidates

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 in young children and infants.
    

Eligibility criteria:

        Inclusion Criteria:

          1. 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);

          2. In good physical and mental health as determined on the basis of medical history,
             laboratory screening tests and general physical and psychological examination;

          3. 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;

          4. Willing to adhere to the prohibitions and restrictions specified in this protocol;

          5. Willing to adhere to the restrictions of containment for duration as specified in the
             protocol;

          6. 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.

             Furthermore, willing to adhere to following restrictions as long as shedding will be
             observed at the end of the containment period:

          7. No intention to travel to the Netherlands and to polio endemic countries (updated list
             will be made available at the start of the study);

          8. No professional handling of food, catering or food production activities;

          9. 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;

         10. No neonatal nursing activities or other professional contact with children under 6
             months old;

        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. Ever having received any OPV in the past;

          3. Having Crohn's disease or ulcerative colitis or having had major surgery of the
             gastrointestinal tract involving significant loss or resection of the bowel;

          4. A known allergy, hypersensitivity, or intolerance to the study vaccine, or to any of
             its components or to any antibiotics;

          5. 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);

          6. 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);

          7. 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;

          8. Indications of drug abuse or excessive use of alcohol at Day 0;

          9. 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;

         10. 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;

         11. 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;

         12. Administration of polio vaccine within 12 months before the start of the study;

         13. 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;

         14. 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.