Phase 1 Novel Live Attenuated Serotype 2 Oral Polio Vaccine Study in Inactivated Polio Vaccine (IPV) Primed Adults

A Phase 1, Blinded, Single Center Study to Evaluate the Safety and Immunogenicity of Two Novel Live Attenuated Serotype 2 Oral Poliovirus Vaccines, Derived From a Modified Sabin 2 Infectious cDNA Clone, in Healthy Adults Previously Primed With Inactivated Polio Vaccine (IPV)

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.

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.

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.