Phase 1 Novel Live Attenuated Serotype 2 Oral Polio Vaccine Study in Inactivated Polio Vaccine (IPV) Primed Adults
Condition: Poliomyelitis
MeSH terms: Poliomyelitis
Study type: Interventional
Phase: Phase 1

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.
    

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.
    

Intervention name(s): Novel OPV2 candidate 1; Novel OPV2 candidate 2
Intervention type(s): Biological; Biological
Intervention description(s): 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.
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Prevention
Keywords: IPV-primed; adults; vaccination; containment; shedding; genetic stability; safety; neurovirulence; novel polio vaccine candidates