NCT04544787

A Phase 2 Study to Evaluate the Safety and Immunogenicity of Two Oral Poliovirus Vaccine Candidates

A Phase 2, Partial Blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate the Safety and Immunogenicity of Two Novel Live Attenuated Serotype 2 Oral Poliovirus Vaccines Candidates, in Healthy Adults Previously Vaccinated With Oral Polio Vaccine (OPV) or Inactivated Polio Vaccine (IPV), Compared With Historical Controls Given Sabin OPV2 or Placebo

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 250 (actual)
• Sponsor: Pierre Van Damme · Academic / Other
• Sex: All
• Age: 18 Years – 50 Years
• Healthy volunteers: Accepted

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.

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. The novel vaccine will eventually be licensed based on 3 criteria: a similar safety profile to the currently licensed monovalent OPV2 (mOPV2) of the Sabin strain, non-inferior immunogenicity, and reduced reversion to virulence. 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

• Poliomyelitis

Interventions

Type	Name	Description
BIOLOGICAL	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.
BIOLOGICAL	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.
BIOLOGICAL	Placebo	sugar syrup, propylene glycol (Sirupus simplex, Propylenglycolum, European Pharmacopoeia)

Timeline

• Start date: 2018-10-22
• Primary completion: 2019-01-31
• Completion: 2019-05-08
• First posted: 2020-09-10
• Last updated: 2021-10-15
• Results posted: 2021-10-15

Locations

2 sites across 1 country: Belgium