A Phase 2 Study to Evaluate the Safety and Immunogenicity... | NCT04544787

NCT04544787

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
2018-001684-22	EudraCT Number

Status Module

Name	Class
Bill and Melinda Gates Foundation	OTHER
Centers for Disease Control and Prevention	FED
PATH	OTHER
Celerion

Description Module

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).

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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

Interventions

Name	Type	Description	Arm Group Labels	Other Names
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.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

Measure	Description	Time Frame
Number of Former OPV Recipients With Solicited Adverse Events Within 7 Days of Vaccination With Novel OPV2	Participants were asked to complete 7-day diary cards soliciting systemic adverse events and daily oral temperature. Solicited events comprised selected signs and symptoms including headache, fatigue, myalgia, arthralgia, paresthesia, anesthesia, paralysis, nausea, vomiting, diarrhea and abdominal pain, or fever defined as a temperature of 37.5°C or higher. AEs were graded as mild (easily tolerated with minimal discomfort or temperature 37.5°C to 38.0°C), moderate (sufficiently discomforting to interfere with normal everyday activities, or temperature 38.1°C to 39.0°C), or severe (preventing normal everyday activities, or temperatures higher than 39.0°C). AEs were assessed by the investigator for causality. Probably related suggests that a reasonable temporal sequence of the AE with vaccine administration exists and, in the Investigator's clinical judgment, it is likely that a causal relationship exists between the vaccine administration and the AE,

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

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;
Administration of any polio vaccine within 12 months before the start of the study;
Having had a transfusion of any blood product or application of immunoglobulins within the 4 weeks prior to the first administration of study vaccine or during the study;
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, or was a study subject in the historical control studies UAM1 or UAT1 or in the study UAM4a (NCT03430349);
Having a family or household member participating in the study CVIA 065 (NCT04232943) or being a study subject in the study CVIA 065.

Name	Affiliation	Role
Pierre Van Damme, Prof. MD	Centre for the evaluation of vaccination	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Centre for the Evaluation of Vaccination, Vaccine & Infectious Disease Institute, University of Antwerp		Wilrijk	Antwerp	2610	Belgium

PubMed Identifier	Type	Citation	Retractions
33308429	Result	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.
38218668

Arm/Group Information

ID	Title	Description
FG000	Group 1: OPV-vaccinated - One Dose of Novel OPV2 Candidate 1	Participants previously vaccinated with OPV received one dose of novel oral polio vaccine type 2 (nOPV2) candidate 1 on study Day 0, administered orally as six drops (0.3 mL total; approximately 10⁶ 50% cell culture infectious dose units [CCID50]).
FG001	Group 2: OPV-vaccinated - Two Doses of Novel OPV2 Candidate 1	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).
FG002	Group 3: OPV-vaccinated - One Dose of Novel OPV2 Candidate 2	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).
FG003	Group 4: OPV-vaccinated - Two Doses of Novel OPV2 Candidate 2	Participants previously vaccinated with OPV 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).
FG004	Group 5: IPV-vaccinated - Two Doses of Novel OPV2 Candidate 1	Participants previously vaccinated with only 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).
FG005	Group 6: IPV-vaccinated - Two Doses of Novel OPV2 Candidate 2	Participants previously vaccinated with only 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).
FG006	Group 7: IPV-vaccinated - Two Doses of Placebo	Participants previously vaccinated with only IPV received two doses of placebo 28 days apart (Day 0 and Day 28), administered orally as six drops (0.3 mL total).

ID	Title	Description
BG000	Group 1: OPV-vaccinated - One Dose of Novel OPV2 Candidate 1	Participants previously vaccinated with OPV received one dose of novel OPV2 candidate 1 on study Day 0.
BG001	Group 2: OPV-vaccinated - Two Doses of Novel OPV2 Candidate 1

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type	Title	Description	Population Description	Reporting Status	Anticipated Posting Date	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Time Frame	Units Analyzed	Denominator Units Selected	Arm/Group Information	Denominators	Classes	Analyses
Primary	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.	The total vaccinated (TV) population includes all randomized participants who received at least one dose of study vaccine.	Posted		Count of Participants		Participants		Up to 42 days after each vaccination

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Group 1: OPV-vaccinated - One Dose of Novel OPV2 Candidate 1	Participants previously vaccinated with OPV received one dose of novel OPV2 candidate 1 on study Day 0.

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Crohn's Disease	Gastrointestinal disorders	MedDRA (22.0)	Systematic Assessment

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Upper Respiratory Tract Infection	Infections and infestations	MedDRA (22.0)	Systematic Assessment

Title	Organization	Phone	Extension	Email
Pierre Van Damme, MD, PhD	University of Antwerp	+32 3 265 21 30		pierre.vandamme@uantwerpen.be

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Dec 20, 2018	Sep 5, 2021	Prot_000.pdf
SAP	No	Yes	No	Statistical Analysis Plan	May 10, 2019	Sep 6, 2021	SAP_001.pdf

ID	Term
D011051	Poliomyelitis

ID	Term
D009187	Myelitis
D002494	Central Nervous System Infections
D007239	Infections
D004769	Enterovirus Infections

ID	Title	Description
OG000	Group 1: OPV-vaccinated - One Dose of Novel OPV2 Candidate 1	Participants previously vaccinated with OPV received one dose of novel OPV2 candidate 1 on Day 0.
OG001	Group 2: OPV-vaccinated - Two Doses of Novel OPV2 Candidate 1	Participants previously vaccinated with OPV received two doses of novel OPV2 candidate 1 28 days apart (Day 0 and Day 28).
OG002	Group 3: OPV-vaccinated - One Dose of Novel OPV2 Candidate 2	Participants previously vaccinated with OPV received one dose of novel OPV2 candidate 2 on study Day 0.
OG003	Group 4: OPV-vaccinated - Two Doses of Novel OPV2 Candidate 2	Participants previously vaccinated with OPV received two doses of novel OPV2 candidate 2 28 days apart (Day 0 and Day 28).
OG004	Group 5: IPV-vaccinated - Two Doses of Novel OPV2 Candidate 1	Participants previously vaccinated with only IPV received two doses of novel OPV2 candidate 1 28 days apart (Day 0 and Day 28).
OG005	Group 6: IPV-vaccinated - Two Doses of Novel OPV2 Candidate 2	Participants previously vaccinated with only IPV received two doses of novel OPV2 candidate 2 28 days apart (Day 0 and Day 28).
OG006	Group 7: IPV-vaccinated - Two Doses of Placebo	Participants previously vaccinated with only IPV received two doses of placebo 28 days apart (Day 0 and Day 28).