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

NCT04544787 | Completed Phase 2 Results DMC

• 2 other identifiers: UAM42018-001684-22
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Poliomyelitis

Keywords

IPV-primed; adults; vaccination; shedding; genetic stability; safety; neurovirulence; novel polio vaccine candidates

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Serious Adverse Events (SAEs) and Severe Adverse Events

  An SAE is any untoward medical occurrence that at any dose met any of the following conditions: * Resulted in death; * Was life-threatening; * Required inpatient hospitalization or prolongation of existing inpatient hospitalization; * Resulted in persistent or significant disability/incapacity; * Was a congenital anomaly/birth defect; * Was medically important. A solicited AE is a pre-selected sign or symptom that occurred within 7 days after each dose, whereas unsolicited AEs were collected throughout the study. Solicited AEs included headache, fatigue, myalgia, arthralgia, paresthesia, anesthesia, paralysis, nausea, vomiting, diarrhea, abdominal pain, and fever. A severe AE is an AE that prevented normal everyday activities and which was not classified as an SAE. A related AE is an AE the investigator considered probably or possibly caused by the study vaccine, meaning that there was a reasonable temporal association or the AE was not attributable to other conditions.

  Up to 42 days after each vaccination

• Seroprotection Rate After a Single Dose of Novel OPV2 in Former OPV Recipients

  Seroprotection rate was defined as the percentage of participants with anti-type 2-specific poliovirus neutralizing antibody titers ≥ 1:8. Neutralizing antibodies against poliovirus type 2 were determined using the World Health Organization (WHO) standard microneutralization assay (WHO EPI GEN 93.9). The lower limit of quantitation (LLOQ) was 5.7 and the upper limit of quantitation (ULOQ) was 1448.

  Baseline (Day 0 prior to vaccination) and Day 28

Secondary Outcomes (11)

• Number of Former OPV Recipients With Solicited Adverse Events Within 7 Days of Vaccination With Novel OPV2

  Up to 7 days after each dose (Day 0-7 post-dose 1 and Day 28-35 post-dose 2)

• Number of Former IPV Recipients With Solicited Adverse Events After Vaccination With Novel OPV2

  7 days post-dose (Day 0-7 post-dose 1 and and Day 28-35 post-dose 2)

• Number of Participants With Unsolicited Adverse Events

  Up to 42 days after each vaccination

• Number of Former OPV Recipients With Clinically Relevant Laboratory Abnormalities Up to 28 Days After Each Vaccination

  Day 0, Day 7, Day 14, and Day 28 for Groups 1-4 and at Day 35, Day 42, and Day 56 for participants in Groups 2 and 4

• Number of Former IPV Recipients With Clinically Relevant Laboratory Abnormalities Up to 28 Days After Each Vaccination

  Day 0, Day 7, Day 14, Day 28, Day 35, Day 42 and Day 56

Study Arms (7)

Group 1: One Dose of Novel OPV2 Candidate 1

EXPERIMENTAL

Participants previously vaccinated with oral polio vaccine (OPV) received one dose of novel OPV2 candidate 1 on Day 0, administered orally as six drops (0.3 mL total; approximately 10⁶ 50% cell culture infectious dose units \[CCID50\]).

Biological: Novel OPV2 candidate 1

Group 2: Two Doses of Novel OPV2 Candidate 1

EXPERIMENTAL

Participants previously vaccinated with OPV received two doses of novel OPV2 candidate 1 28 days apart (Day 0 and Day 28), administered orally as six drops (0.3 mL total; approximately 10⁶ CCID50).

Biological: Novel OPV2 candidate 1

Group 3: One Dose of Novel OPV2 Candidate 2

EXPERIMENTAL

Participants previously vaccinated with OPV received one dose of novel OPV2 candidate 2 on study Day 0, administered orally as six drops (0.3 mL total; approximately 10⁶ CCID50).

Biological: Novel OPV2 candidate 2

Group 4: Two Doses of Novel OPV2 Candidate 2

EXPERIMENTAL

Participants previously vaccinated OPV received two doses novel OPV2 candidate 2 28 days apart (Day 0 and Day 28), administered orally as six drops (0.3 mL total; approximately 10⁶ CCID50).

Biological: Novel OPV2 candidate 2

Group 5: Two Doses of Novel OPV2 Candidate 1

EXPERIMENTAL

Participants previously vaccinated with inactivated polio vaccine (IPV) received two doses of novel OPV2 candidate 1 28 days apart (Day 0 and Day 28), administered orally as six drops (0.3 mL total; approximately 10⁶ CCID50).

Biological: Novel OPV2 candidate 1

Group 6: Two Doses of Novel OPV2 Candidate 2

EXPERIMENTAL

Participants previously vaccinated with IPV received two doses of novel OPV2 candidate 2 28 days apart (Day 0 and Day 28), administered orally as six drops (0.3 mL total; approximately 10⁶ CCID50).

Biological: Novel OPV2 candidate 2

Group 7: Two Doses of Placebo

PLACEBO COMPARATOR

Participants previously vaccinated with IPV received two doses of placebo 28 days apart (Day 0 and Day 28), administered orally as six drops (0.3 mL total).

Biological: Placebo

Interventions

Novel OPV2 candidate 1 BIOLOGICAL

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.

Group 1: One Dose of Novel OPV2 Candidate 1; Group 2: Two Doses of Novel OPV2 Candidate 1; Group 5: Two Doses of Novel OPV2 Candidate 1

Novel OPV2 candidate 2 BIOLOGICAL

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.

Group 3: One Dose of Novel OPV2 Candidate 2; Group 4: Two Doses of Novel OPV2 Candidate 2; Group 6: Two Doses of Novel OPV2 Candidate 2

Placebo BIOLOGICAL

sugar syrup, propylene glycol (Sirupus simplex, Propylenglycolum, European Pharmacopoeia)

Group 7: Two Doses of Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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;
• 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;
• Having residence in Belgium;
• In good physical and mental health as determined on the basis of medical history and general physical examination performed at Day 0;
• 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;
• Willing to adhere to the prohibitions and restrictions specified in this protocol;
• 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.

You may not qualify if:

• 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;
• For Groups 5, 6 and 7: ever having received any OPV in the past;
• 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;
• Professional handling of food, catering or food production activities during the total duration of the study;
• Having Crohn's disease or ulcerative colitis or having had major surgery of the gastrointestinal tract involving significant loss or resection of the bowel;
• A known allergy, hypersensitivity, or intolerance to the study vaccine or the placebo, or to any of their components or to any antibiotics;
• 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 \[LLN\]);
• 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;
• Neonatal nurses or others having professional contact with children under 6 months of age during the total duration of the study;
• 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);
• 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;
• Indications of drug abuse or excessive use of alcohol at Day 0 (males: \> 21 units/week; females \> 14 units/week);
• 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;
• 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;
• 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;

Sponsors & Collaborators

• Pierre Van Damme: lead
• Bill and Melinda Gates Foundation: collaborator
• Centers for Disease Control and Prevention: collaborator
• PATH: collaborator
• Celerion: collaborator

Study Sites (2)

Centre for the Evaluation of Vaccination, Vaccine & Infectious Disease Institute, University of Antwerp

Wilrijk, Antwerp, 2610, Belgium

Location

CEVAC, Center for Vaccinology, Ghent University Hospital

Ghent, 9000, Belgium

Location

Related Publications (2)

• De Coster I, Leroux-Roels I, Bandyopadhyay AS, Gast C, Withanage K, Steenackers K, De Smedt P, Aerssens A, Leroux-Roels G, Oberste MS, Konopka-Anstadt JL, Weldon WC, Fix A, Konz J, Wahid R, Modlin J, Clemens R, Costa Clemens SA, Bachtiar NS, Van Damme P. Safety and immunogenicity of two novel type 2 oral poliovirus vaccine candidates compared with a monovalent type 2 oral poliovirus vaccine in healthy adults: two clinical trials. Lancet. 2021 Jan 2;397(10268):39-50. doi: 10.1016/S0140-6736(20)32541-1. Epub 2020 Dec 9.

  PMID: 33308429 RESULT

• Thompson KM, Kalkowska DA, Kidd SE, Burns CC, Badizadegan K. Trade-offs of different poliovirus vaccine options for outbreak response in the United States and other countries that only use inactivated poliovirus vaccine (IPV) in routine immunization. Vaccine. 2024 Feb 6;42(4):819-827. doi: 10.1016/j.vaccine.2023.12.081. Epub 2024 Jan 12.

  PMID: 38218668 DERIVED

MeSH Terms

Conditions

Poliomyelitis

Condition Hierarchy (Ancestors)

Myelitis; Central Nervous System Infections; Infections; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Virus Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Neuroinflammatory Diseases; Neuromuscular Diseases

Results Point of Contact

• Title: Pierre Van Damme, MD, PhD
• Organization: University of Antwerp

pierre.vandamme@uantwerpen.be

+32 3 265 21 30

Study Officials

• Pierre Van Damme, Prof. MD

  Centre for the evaluation of vaccination

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Full Professor

Model Details: 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).

Study Record Dates

• First Submitted: July 14, 2020
• First Posted: September 10, 2020
• Study Start: October 22, 2018
• Primary Completion: January 31, 2019
• Study Completion: May 8, 2019
• Last Updated: October 15, 2021
• Results First Posted: October 15, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

BE (2)